Podcasts about rnai

We love to hear from our listeners. Send us a message. On today's episode, Tolga Tanguler, EVP and Chief Commercial Officer at Alnylam Pharmaceuticals, talks about commercializing RNAi therapies, how they fit into health insurance reimbursement systems, the company's use of value-based contracts, and building therapeutic franchise "skyscrapers." Tangular also shares his thoughts on commercializing RNAi therapies for larger patient populations, compared with rare disease populations, and reflects on changes in the biopharmaceutical sales and promotion model.This episode is brought to you by Avantor. For more information, visit avantorsciences.comAccess this and hundreds of episodes of the Business of Biotech videocast under the Business of Biotech tab at lifescienceleader.com. Subscribe to our monthly Business of Biotech newsletter. Get in touch with guest and topic suggestions: ben.comer@lifescienceleader.comFind Ben Comer on LinkedIn: https://www.linkedin.com/in/bencomer/

Flera amerikanska universitet har fått krav på sig att bland annat ändra sin antagning. Ansedda Harvard nobbar kraven och fråntas 2 miljarder dollar. Lyssna på alla avsnitt i Sveriges Radio Play. Hör USA-korrespondenten Ginna Lindberg om kraven och om Harvard-rektorns svar till Trump. Det handlar också om att en liten RNAi-molekyl provas mot de varroa-kvalster som är ett problem i bikupor, och om att läsa böcker respektive lyssna på dem.Programledare och producenter:Gustaf Klaringustaf.klarin@sverigesradio.seCamilla Widebeckcamilla.widebeck@sverigesradio.se

Baylor College of Medicineの山本慎也さんがゲスト。前編。ツールとしてハエを使うNeuroscientistと脳を見ているハエGeneticistの違い、ハエForward geneticsからヒト希少疾患研究に繋がった経緯、Living test tubeとしてのハエの魅力、Reverse geneticsによるヒト化ハエのRare disease・Common disease・感染症研究への応用について (3/28収録)Show Notes (番組HP):山本さんラボHP(更新が滞りがち) LinkedInベイラー医科大学動物育種繁殖学教室今川和彦先生着床現象は種特異的臍帯形成などに異常があるVps26a(Hβ58)の変異マウス 1 2Hugo BellenJan and Dan Duncan Neurological Research InstituteHugoによるレビューScott Emr武田洋幸先生多羽田哲也先生後藤聡先生Retromer ComplexとWnt signalingに関する論文(４本じゃなくて５本でした：Dev Cell x3 + NCB x2) 1 2 3 4 5Gerry RubinAllan SpradlingThomas CechSeymour Benzer追悼記事 1 2Thomas Hunt Morganハエ研究の黎明期メンデルによる遺伝子の提唱と再発見津田梅子先生がMorganのところでやった仕事メンデルの法則Hermann Muller放射線による遺伝子の破壊・改変を発見Marie Curieの死因発生生物学者と遺伝学者は仲が悪かった最初のNotchミュータントの欠けている翅HomozygousだとNeurogenic phenotypeAntennapediaとUltrabithoraxハエの記憶に関する最初の報告この系をつかった最初のL&Mの変異体、dunceの論文(cAMPの分解酵素)サーカディアンリズムのperiod変異体の論文ShibireはDynaminに関する変異体Kir2.1NaChBac遺伝学的手法を用いてハエの神経活動を操作する(リンク先Table2)GSAによるショウジョウバエの学会CSHLのNeurobiology of DrosophilaJaneliaのconferenceNRでショウジョウバエを扱った回Forward genetics(順遺伝学)とReverse genetics(逆遺伝学)Chemical mutagenesisではEMSやENUがよく用いられるarmadillo (arm)＝ハエのβ-Catenin Christiane Nüsslein-VolhardEric WieschausThe Heidelberg screen回顧録MARCM利根川先生のCaMKII-Creを用いたconditional KO (訂正：CaMKIIをcKOしたんじゃなくて、CaMKII-Creを用いて別の遺伝子をcKOしてましたね。 by 山)Flp/FRTとEMSを組み合わせることによるモザイク・スクリーニングの初出論文　レビューハエのElectroretinogram(ERG) 1 2ｍusashiとハエの感覚毛の４細胞感覚ユニット岡野先生らによるmusashi発見博士の時にやったスクリーニング結果をヒト希少疾患と結びつけたCell論文ApoE2とE4: 逆でした (by 山)ヒトゲノム計画におけるBaylorの貢献HapMap project1000 Genomes projectCenter for Mendelian GenomicsRichard GibbsJames LupskiSynteny(シンテニー)Complementation test(相補性検定)LiqinのMARCM EMS Screenの例Hippo signaling pathway レビューこのPathwayのコアのhippoという遺伝子は４つのラボで同時期にFLP/FRTスクリーニングなどを通じてみつかりました（Cell２本、NCB２本）  1 2 3 4ハエのin vivo RNAiのライブラリ 1 2 3RNAiとEMSで見えてくる遺伝子が違う：Cell論文のFig. 2CRISPRも含めて、Mammalの例 1 2Rett Syndromeの原因遺伝子はMECP2Huda Zoghbiハエ遺伝子のヒト化T2A-GAL4Kozak-GAL4Mutationの機能的分類(Muller's morphs)Undiagnosed Diseases Network(UDN)NIH CommonfundBRAIN initiativeUDN Model Organisms Screening Center

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world.Sanofi and Alnylam have received FDA approval for the first RNAi treatment for hemophilia, with the drug, Qfitlia, indicated for both hemophilia A and B. This approval is significant as it can be given regardless of the presence of neutralizing antibodies against clotting factors VIII or IX. However, the sudden departure of FDA director Peter Marks has caused uncertainty in the biopharma industry. In other news, Vertex has cut a diabetes asset but analysts remain optimistic about their phase III option. Lilly's RNA silencer has shown promising results in lowering a key cardiovascular biomarker. Trilink is offering custom guide RNAs for CRISPR workflow to accelerate therapy discoveries. Despite market challenges, the cell and gene therapy sector has seen a 30% investment surge. Companies like Amgen, Aldeyra, and Argenx are among those with upcoming FDA actions. Arbutus has announced layoffs, while big pharmas are pushing boundaries in radiopharmaceuticals. Michelle Werner of AltoRNA is focused on making better drugs. Safety questions are looming in Duchenne as Dyne and Wave plan FDA filings. There are job opportunities available in data management and program leadership within the biopharma industry.Moving on to other news, several big pharmaceutical companies such as Novartis, Bayer, AstraZeneca, Bristol Myers Squibb, and Eli Lilly are competing in the radiopharmaceuticals market, which is projected to be worth over $13 billion by 2033. The FDA is expected to announce decisions on therapies for dry eye disease soon. Michelle Werner, CEO of AllTrna, is focused on developing trna-based treatments for various diseases.Safety concerns are emerging in the Duchenne muscular dystrophy space as companies like Dyne and Wave plan FDA filings. The EU rejected Lilly's Alzheimer's drug Kisunla, Biontech's bispecific showed promise in treating SCLC patients, and Wave's duchenne exon-skipper reversed muscle damage in a mid-stage trial. Job opportunities within the biopharma industry were also highlighted for those interested.Thank you for tuning in to Pharma and Biotech daily - keeping you updated on all the latest news in the world of pharmaceuticals and biotechnology.

President Donald Trump doubled down on tariff threats targeting pharma, saying additional levies on pharmaceuticals will come “at some point,” per CNBC. Meanwhile, Johnson & Johnson became the latest big pharma to respond to Trump's warning of potential tariffs if companies don't reshore their manufacturing, announcing a massive $55 billion U.S. manufacturing and R&D investment. Not all companies are on board, however: AstraZeneca is looking eastward, pumping $2.5 billion into a new research facility in Beijing.    Also on the policy front, Trump nominated acting CDC director Susan Monarez for the top job after pulling his first nominee, Dave Weldon, days before his senate hearing was expected to begin. If confirmed, Monarez would be the first CDC director since 1953 to not have a medical degree; she holds a Ph.D. in microbiology and immunology from the University of Wisconsin.   In weight loss news, Novo Nordisk is paying China-based United Laboratories $200 million upfront to license a triple agonist of the GLP-1, GIP and glucagon receptors that could one day compete with Eli Lilly's retatrutide. And BioSpace examines the next great challenge for GLP-1s: oral formulation manufacturing.    Two more therapeutic spaces in focus last week are Duchenne muscular dystrophy and spinal muscular atrophy, where companies including Dyne Therapeutics, REGENXBIO and Novartis presented new data on their respective candidates. And the Duchenne community continued to react to news of the death of a patient taking Sarepta's approved gene therapy Elevidys.  In cardiovascular news, Alnylam won a much-anticipated approval for Amvuttra as the first RNAi silencer for transthyretin amyloid cardiomyopathy, setting up a three-way race with Pfizer's tafamidis—marketed as Vyndaqel and Vyndama—and BridgeBio's Attruby. Next up is Milestone Therapeutics' CARDAMYST in paroxysmal supraventricular tachycardia, which has a PDUFA date of March 27.   Finally, the saga of Cassava Sciences' Alzheimer's hopeful simufilam is over, as the company announced it has ended development of the controversial candidate.   

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.The CDC has rescheduled a vaccine meeting for April, while President Trump is considering Texas Republican Michael Burgess as the new director of the agency. J&J's Tremfya has won approval for expansion in treating Crohn's disease, while Adaptimmune is facing financial uncertainty despite sales of its T cell therapy. Alnylam's Amvuttra has been approved as the first RNAi silencer for a rare type of cardiomyopathy, setting up competition with Pfizer and BridgeBio. Sino Biological has developed reagents for the 2025-2026 influenza vaccine strains. In other news, J&J plans to boost US manufacturing following tariff threats, Novartis' Fabhata has been approved as the first therapy for a rare kidney disease, and Sanofi commits up to $1.9 billion for Dren Bio's bispecific antibody for autoimmune diseases. Paratek has acquired Optinose for up to $330 million, Purdue Pharma has filed for bankruptcy again to support an opioid settlement, and Novartis' Zolgensma has been found effective in older children.The FDA has approved Alnylam's Amvuttra as the first RNAi silencer for a rare type of cardiovascular disease called ATTR-CM, following the approval of BridgeBio's Attruzy for the same condition. This approval has sparked a three-way race in the rapidly expanding space, with Pfizer's Tafamidis also in the competition. Alnylam is optimistic about Amvuttra's unique mechanism of action, which targets the disease at its source by rapidly reducing the disease-causing TTR protein. This approval comes after Attruzy was also approved for polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in June 2022. This development has brought cardiovascular disease back into the spotlight, with other companies launching new drugs and treatments for various heart conditions.

Welcome to HCPLive's 5 Stories in Under 5—your quick, must-know recap of the top 5 healthcare stories from the past week, all in under 5 minutes. Stay informed, stay ahead, and let's dive into the latest updates impacting clinicians and healthcare providers like you! Interested in a more traditional, text rundown? Check out the HCPFive! New ACP Guidelines Recommend Adding Triptan to NSAID or Acetaminophen for Migraines The American College of Physicians now recommends adding a triptan to NSAIDs or acetaminophen for moderate to severe acute migraines and urges clinicians to initiate combination therapy early. Automated Insulin Delivery Effectively Lowers HbA1c in Type 2 Diabetes  Tandem Diabetes Care's Control-IQ+ automated insulin delivery system led to greater HbA1c reduction than continuous glucose monitoring alone in adults with insulin-requiring type 2 diabetes. FDA Approves Guselkumab (Tremfya) For Crohn's Disease  The FDA approved guselkumab for moderately to severely active Crohn's disease based on phase 3 trial data demonstrating superior efficacy over ustekinumab on endoscopic endpoints. FDA Approves Oral Iptacopan (Fabhalta) as First C3 Glomerulopathy Therapy  The FDA approved iptacopan as the first therapy for C3 glomerulopathy, with phase 3 data showing significant proteinuria reduction and sustained efficacy at 12 months. FDA Approves Vutrisiran (AMVUTTRA) for ATTR-CM  The FDA expanded vutrisiran's approval for cardiomyopathy in transthyretin-mediated amyloidosis, making it the first RNAi therapeutic to reduce cardiovascular mortality and hospitalizations in ATTR-CM.

A patient with Duchenne muscular dystrophy taking Sarepta's gene therapy Elevidys has died of acute liver failure, possibly related to a recent viral infection. Sarepta, which said it will update Elevidys' label to reflect the new safety signal, saw its shares drop 22% on the news but analysts still seem positive on the drug, as treatment options for Duchenne remain limited.Meanwhile, both AstraZeneca and Taiho Pharmaceuticals announced acquisitions worth up to $1 billion or more in two sizzling therapeutic spaces, cell therapy and antibody-drug conjugates, respectively.Despite canceling a vaccine advisory committee late last month, the FDA on Thursday selected flu strains to be targeted in the upcoming 2025-2026 flu season. And at another federal agency, the Centers for Disease Control and Prevention, employees will have to wait a bit longer to see who will take the helm under Donald Trump, as the president's nominee, Dave Weldon, was pulled hours before he was set to appear before a Senate committee on Thursday. Like HHS Secretary Robert F. Kennedy Jr., Weldon has expressed anti-vaccine views in the past, particularly his continued suggestion of the link between vaccines and autism. Guggenheim Partners called the move to revoke Weldon's nomination “a positive sign for reigning in vaccine criticism.”In the weight loss arena, BioSpace takes deep dives into the tendency for biopharma to develop fast-followers, or me-too drugs—following a pattern seen with PD-1 checkpoint inhibitors after the approvals of Merck's Keytruda and Bristol Myers Squibb's Opdivo. One key difference between these two markets, however, is that when it comes to GLP-1s for weight loss, patients are not staying on these medicines. Drug developers are trying several approaches to improve treatment persistence, including titration, combinations and even secondary drugs that address side effects. They're also making other moves to differentiate themselves, including focusing on overall health outcomes—in areas like cardiovascular, sleep apnea and kidney disease.Following on BioSpace's coverage of the major patent cliffs that many Big Pharma companies are facing in coming years, we also take a look back at some of the companies that have already weathered such loss of exclusivity. It's rarely a straightforward story of sales crashing off patent, as companies take various tacks to extend their blockbuster sales.Finally, the cardiovascular space is expecting some movement this week. First, Alnylam is anticipating a decision on its RNAi silencer Amvuttra in ATTR-CM. An approval—which is widely expected—would make three companies on the market in this rapidly expanding space after Pfizer's tafamidis was approved in May of 2019, and BridgeBio's Attruby got the greenlight in November last year. And second, Milestone Pharmaceutical has a PDUFA coming up for etripamil in paroxysmal supraventricular tachycardia.

Kick off 2025 with an insightful conversation featuring Dr. David Peck, Director of Research and Education at Betterbee, as he joins Jeff and Becky to discuss the year's hottest trends and challenges in beekeeping. From cutting-edge varroa control methods to potential impacts of the invasive yellow-legged hornet, this episode is packed with valuable information for beekeepers of all levels. David shares exciting updates on new mite control products, including VarroxSan and RNAi technology, and highlights the growing popularity of biotechnical strategies like brood breaks. The discussion also dives into the concerning presence of yellow-legged hornets in the southeastern U.S., exploring their potential impact on honey bee colonies and the industry's efforts to contain them. On a lighter note, discover how Betterbee's innovative products, like the upgraded Hogg Halfcomb system, make comb honey production more accessible for beekeepers. Plus, hear about Dr. Peck's passion for educating and empowering beekeepers through programs like the Eastern Apicultural Society's Master Beekeeper certification. Whether you're gearing up for the new season or simply looking to stay ahead of emerging trends, this episode is a must-listen! Listen Today! Websites we recommend: Honey Bee Health Coalition: https://honeybeehealthcoalition.org The National Honey Board: https://honey.com Honey Bee Obscura Podcast: https://honeybeeobscura.com 2 Million Blossoms - The Podcast: https://2millionblossoms.com Copyright © 2025 by Growing Planet Media, LLC     ______________ Betterbee is the presenting sponsor of Beekeeping Today Podcast. Betterbee's mission is to support every beekeeper with excellent customer service, continued education and quality equipment. From their colorful and informative catalog to their support of beekeeper educational activities, including this podcast series, Betterbee truly is Beekeepers Serving Beekeepers. See for yourself at www.betterbee.com This episode is brought to you by Global Patties! Global offers a variety of standard and custom patties. Visit them today at http://globalpatties.com and let them know you appreciate them sponsoring this episode!  Thanks to Bee Smart Designs as a sponsor of this podcast! Bee Smart Designs is the creator of innovative, modular and interchangeable hive systems made in the USA using recycled and American sourced materials. Bee Smart Designs - Simply better beekeeping for the modern beekeeper. Thanks to Strong Microbials for their support of Beekeeping Today Podcast. Find out more about their line of probiotics in our Season 3, Episode 12 episode and from their website: https://www.strongmicrobials.com Thanks for Northern Bee Books for their support. Northern Bee Books is the publisher of bee books available worldwide from their website or from Amazon and bookstores everywhere. They are also the publishers of The Beekeepers Quarterly and Natural Bee Husbandry. _______________ We hope you enjoy this podcast and welcome your questions and comments in the show notes of this episode or: questions@beekeepingtodaypodcast.com Thank you for listening!  Podcast music: Be Strong by Young Presidents; Epilogue by Musicalman; Faraday by BeGun; Walking in Paris by Studio Le Bus; A Fresh New Start by Pete Morse; Wedding Day by Boomer; Christmas Avenue by Immersive Music; Red Jack Blues by Daniel Hart; Original guitar background instrumental by Jeff Ott. Beekeeping Today Podcast is an audio production of Growing Planet Media, LLC Copyright © 2025 by Growing Planet Media, LLC

Alnylam Pharmaceuticals CEO Yvonne Greenstreet discusses why RNAI can be used to treat an array of diseases, the company's medicines using this technology, and more.

Alnylam Pharmaceuticals chief scientific officer Kevin Fitzgerald on the past, present & future of RNA interference medicines.

When I think of digital biology, I think of Patrick Hsu—he's the prototype, a rarified talent in both life and computer science, who recently led the team that discovered bridge RNAs, what may be considered CRISPR 3.0 for genome editing, and is building new generative A.I. models for life science. You might call them LLLMs-large language of life models. He is Co-Founder and a Core Investigator of the Arc Institute and Assistant Professor of Bioengineering and Deb Faculty Fellow at the University of California, Berkeley.Above is a brief snippet of our conversation. Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Here's the transcript with links to the audio and external links to relevant papers and things we discussed.Eric Topol (00:06):Well hello, it's Eric Topol with Ground Truths and I'm really delighted to have with me today Patrick Hsu. Patrick is a co-founder and core investigator at the Arc Institute and he is also on the faculty at the University of California Berkeley. And he has been lighting things up in the world of genome editing and AI and we have a lot to talk about. So welcome, Patrick.Patrick Hsu (00:29):Thanks so much. I'm looking forward to it. Appreciate you having me on, Eric.The Arc InstituteEric Topol (00:33):Well, the first thing I'd like to get into, because you're into so many important things, but one that stands out of course is this Arc Institute with Patrick Collison who I guess if you can tell us a bit about how you two young guys got to meet and developed something that's really quite unique that I think brings together investigators at Stanford, UCSF, and Berkeley. Is that right? So maybe you can give us the skinny about you and Patrick and how all this got going.Patrick Hsu (01:05):Yeah, sure. That sounds great. So we started Arc with Patrick C and with Silvana Konermann, a longtime colleague and chemistry faculty at Stanford about three years ago now, though we've been physically operational just over two years and we're an independent research institute working at the interface of biomedical science and machine learning. And we have a few different aspects of our model, but our overall mission is to understand and treat complex human diseases. And we have three pillars to our model. We have this PI driven side of the house where we centrally fund our investigators so that they don't have to write grants and work on their very best ideas. We have a technical staff side of the house more like you'd see in a frontier AI lab or in biotech industry where we have professional teams of R&D scientists working cross-functionally on higher level organizational wide goals that we call our institute initiatives.(02:05):One focused on Alzheimer's disease experimentally and one that we call a virtual cell initiative to simulate human biology with AI foundation models. And our third pillar over time is to have things not just end up as academic papers, but really get things out into the real world as products or as medicines that can actually help patients on the translational side. And so, we thought that some really important scientific programs could be unlocked by enabling new organizational models and we are experimenting at the institutional scale with how we can better organize and incentivize and support scientists to reach these long-term capability breakthroughs.Patrick, Patrick and SilvanaEric Topol (02:52):So the two Patrick's. How did you, one Patrick I guess is a multi-billionaire from Stripe and then there's you who I suspect maybe not quite as wealthy as the other Patrick, how did you guys come together to do this extraordinary thing?Patrick Hsu (03:08):Yeah, no, science is certainly expensive. I met Patrick originally through Silvana actually. They actually met, so funny trivia, all three Arc founders did high school science together. Patrick and Silvana originally met in the European version of the European Young Scientist competition in high school. And Silvana and I met during our PhDs in her case at MIT and I was at Harvard, but we met at the Broad Institute sort of also a collaborative Harvard, MIT and Harvard hospitals Institute based in Kendall Square. And so, we sort of in various pairwise combinations known each other for decades and worked together for decades and have all collectively been really excited about science and technology and its potential to accelerate societal progress. Yet we also felt in our own ways that despite a lot of the tremendous progress, the structures in which we do this work, fund it, incentivize it and roll it out into the real world, seems like it's really possible that we'll undershoot that potential. And if you take 15 years ago, we didn't have the modern transformer that launched the current AI revolution, CRISPR technology, single-cell, mRNA technology or broadly addressable LNPs. That's a tremendous amount of technologies have developed in the next 15 years. We think there's a real unique opportunity for new institutes in the 2020s to take advantage of all of these breakthroughs and the new ones that are coming to continue to accelerate biological progress but do so in a way that's fast and flexible and really focused.Eric Topol (04:58):Yeah, I did want to talk with you a bit. First of all before I get to the next related topic, I get a kick out of you saying you've worked or known each other for decades because I think you're only in your early thirties. Is that right?Patrick Hsu (05:14):I was lucky to get an early start. I first started doing research at the local university when I was 14 actually, and I was homeschooled actually until college. And so, one of the funny things that you got to do when you're homeschooled is well, you could do whatever you want. And in my case that was work in the lab. And so, I actually worked basically full time as an intern volunteer, cut my teeth in single cell patch clamp, molecular biology, protein biochemistry, two photon and focal imaging and kind of spiraled from there. I loved the lab, I loved doing bench work. It was much more exciting to me than programming computers, which was what I was doing at the time. And I think these sort of two loves have kind of brought me and us to where we are today.Eric Topol (06:07):Before you got to Berkeley and Arc, I know you were at Broad Institute, but did you also pick up formal training in computer science and AI or is that something that was just part of the flow?Patrick Hsu (06:24):So I grew up coding. I used to work through problems sets before dinner growing up. And so, it's just something that you kind of learn natively just like learning French or Mandarin.New Models of Funding Life ScienceEric Topol (06:42):That's what I figured. Okay. Now this model of Arc Institute came along in a kind of similar timeframe as the Arena BioWorks in Boston, where some of the faculty left to go to Arena like my friend Stuart Schreiber and many others. And then of course Priscilla and Mark formed the Chan Zuckerberg Institute and its biohub and its support. So can you contrast for one, these three different models because they're both very different than of course the traditional NIH pathway, how Arc is similar or different to the others, and obviously the goal here is accelerating things that are going to really make a difference.Patrick Hsu (07:26):Yeah, the first thing I would say is zooming out. There have been lots of efforts to experiment with how we do science, the practice of science itself. And in fact, I've recently been reading this book, the Demon Under the Microscope about the history of infectious disease, and it talks about how in the 1910s through the 1930s, these German industrial dye manufacturing companies like Bayer and BASF actually launched what became essentially an early model for industrial scale science, where they were trying to develop Prontosil, Salvarsan and some of these early anti-infectives that targeted streptococcus. And these were some of the major breakthroughs that led to huge medical advances on tackling infectious disease compared to the more academic university bound model. So these trends of industrial versus academic labs and different structures to optimize breakthroughs and applications has been a through current throughout international science for the last century.(08:38):And so, the way that we do research today, and that's some of our core tenets at Arc is basically it hasn't always been this way. It doesn't need to necessarily be this way. And so, I think organizational experiments should really matter. And so, there's CZI, Altos, Arena, Calico, a variety of other organizational experiments and similarly we had MRC and Bell Labs and Xerox PARCS, NIBRT, GNF, Google Research, and so on. And so, I think there are lots of different ways that you can organize folks. I think at a high level you can think about ways that you can play with for-profit versus nonprofit structures. Whether you want to be a completely independent organization or if you want to be partnered with universities. If you want to be doing application driven science or really blue sky curiosity driven work. And I think also thinking through internally the types of expertise that you bring together.(09:42):You can think of it like a cancer institute maybe as a very vertically integrated model. You have folks working on all kinds of different areas surrounding oncology or immunotherapy and you might call that the Tower of Babel model. The other way that folks have built institutes, you might call the lily pad model where you have coverage of as many areas of biomedical research as possible. Places like the Whitehead or Salk, it will be very broad. You'll have planned epigenetics, folks looking at RNA structural biology, people studying yeast cell cycle, folks doing in vivo melanoma models. It's very broad and I think what we try to do at Arc is think about a model that you might liken more to overlapping Viking shields where there's sort of five core areas that we're deeply investing in, in genetics and genomics, computation, neuroscience, immunology and chemical biology. Now we really think of these as five areas that are maybe the minimal critical mass that you would need to make a dent on something as complicated as complex human diseases. It's certainly not the only thing that you need, but we needed a critical mass of investigators working at least in these areas.Eric Topol (11:05):Well, yeah, and they really converge on where the hottest advances are being made these days. Now can you work at Arc Institute without being one of these three universities or is it really that you maintain your faculty and your part of this other entity?Patrick Hsu (11:24):So we have a few elements to even just the academic side of the house. We have our core investigators. I'm one of them, where we have dually appointed faculty who retain their latter rank or tenured appointment in their home department, but their labs are physically cited at the Arc headquarters where we built out a lab in Stanford Research Park in Palo Alto. And so, folks move their labs there. They continue to train graduate students based on whatever graduate programs they're formally affiliated with through their university affiliation. And so, we have nearly 40 PhD students across our labs that are training on site every day.(12:03):So in addition to our core investigators, we also have what we call our innovation investigators, which is more of a grant program to faculty at our partner universities. They receive unrestricted funding from us to seed a new project or accelerate an existing area in their group and their labs stay at their home campus and they just get that funding to augment their work. The third way is our technical staff model where folks basically just come work at Arc and many of them also are establishing their own research groups focusing on technology R&D areas. And so, we have five of those technology centers working in molecular engineering, multi-omics, complex cellular models, in vivo models, and in machine learning.Discovery of Bridge RNAsEric Topol (12:54):Yeah, that's a great structure. In fact, just a few months ago, Patrick Collison, the other Patrick came to Stanford HAI where I'm on the board and you've summarized it really well and it's very different than the other models and other entities, companies included that you mentioned. It's really very impressive. Now speaking of impressive on June 26, this past few months ago, which incidentally is coincident with the draft genome in the year 2000, the human sequence. You and your colleagues, perhaps the most impressive jump in terms of an Arc Institute contribution published two papers back-to-back in Nature about bridge RNA: [Bridge RNAs direct programmable recombination of target and donor DNA] and [Structural mechanism of bridge RNA-guided recombination.] And before I get you to describe this breakthrough in genome editing, some would call it genome editing 3.0 or CRISPR 3.0, whatever. But what we have today in the clinic with the approval of CRISPR 1.0 for sickle cell and thalassemia is actually quite crude. I think most people will know it's just a double stranded DNA cleavage with all sorts of issues about repair and it's not very precise. And so, CRISPR 2.0 is supposed to be represented by David Liu's contributions and his efforts at Broad like prime and base editing and then comes yours. So maybe you can tell us about it and how it is has to be viewed as quite an important advance.Patrick Hsu (14:39):The first thing I would say before CRISPR, is that we had RNA interference. And so, even before this modern genome editing revolution with programmable CRISPRs, we had this technology that had a lot of the core selling points as well. Any target will now become druggable to us. We simply need to reprogram a guide RNA and we can get genetic access to things that are intracellular. And I think both the discovery of RNA interference by Craig Mello and Andy Fire or the invention or discovery of programmable CRISPR technologies, both depend on the same fundamental biological mechanism. These non-coding guide RNAs that are essentially a short RNA search string that you can easily reprogram to retarget a desired enzyme function, and natively both RNAi and CRISPR are molecular scissors. Their RNA or DNA nucleases that can be reprogrammed to different regions of the genome or the transcriptome to make a cut.(15:48):And as bioengineers, we have come up with all kinds of creative ways to leverage the ability to make site specific cuts to do all kinds of incredible things including genome editing or beyond transcriptional up or down regulation, molecular imaging and so on and so forth. And so, the first thing that we started thinking about in our lab was, why would mother nature have stopped only RNAi and CRISPR? There probably are lots of other non-coding RNAs out there that might be able to be programmable and if they did exist, they probably also do more complicated and interesting things than just guide a molecular scissors. So that was sort of the first core kind of intuition that we had. The second intuition that we had on the technology side, I was just wearing my biology hat, I'll put on my technology hat, is the thing that we call genome editing today hardly involves the genome.(16:50):It's really you're making a cut to change an individual base or an individual gene or locus. So really you're doing small scale single locus editing, so you might call it gene level or locus level cuts. And what you really want to be able to do is do things at the genome scale at 100 kb, a megabase at the chromosome scale. And I think that's where I think the field will inevitably go if you follow the technology curves of longer and longer range gene sequencing, longer and longer range gene synthesis, and then longer and longer range gene editing. And so, what would that look like? And we started thinking, could there be essentially recombination technologies that allow you to do cut and paste in a single step. Now, the reason for that is the way that we do gene editing today involves a cut and then a multi-step process of cellular DNA repair that resolves the cut to make the exertion or the error prone deletion or the modification that ends up happening.(17:59):And so, it's very complicated and whether that's nucleases or base or prime editing, you're all generally limited to the small-scale single locus changes. However, there are natural mechanisms that have solved this cut and paste problem, right? There are these viruses or bacterial versions of viruses known as phage that have generally been trying to exert their multi kilobase genomes into bacterial hosts and specialize throughout billions of years. So our core thought was, well, if there are these new non-coding RNAs, what kind of functions would we be excited about? Can we look in these mobile genetic elements, these so-called jumping genes for new mechanisms? They're incredibly widespread. Transposons are thought to be some of the most diverse enzyme mechanisms found in nature. And so, we started computationally by asking ourselves a very simple question. If a mobile element inserts itself into foreign DNA and it's able to somehow be programmable, presumably the inside or something encoded in the inside of the element is predictive of some sequence on the outside of the element.(19:15):And so, that was the core insight we took, and we thought let's look across the boundaries of many different mobile genetic elements and we zoomed in on a particular sub family of these MGE known as insertion sequence (IS) elements which are the most autonomous minimal transposons. Normally transposons have all kinds of genes that they use to hitchhike around the genomic galaxy and endow the bacterial host with some fitness advantage like some ability to metabolize some copper and some host or some metal. And these IS elements have only the enzymes that they need to jump around. And if you identify the boundaries of these using modern computational methods, this is actually a really non-trivial problem. But if you solve that problem to figure out with nucleotide resolution where the element boundaries end and then you look for the open reading frame of the transposases enzyme inside of this element, you'll find that it's not just that coding sequence.(20:19):There are also these non-coding flanks inside of the element boundaries. And when we looked across the non-coding, the entire IS family tree, there are hundreds of these different types of elements. We found that this particular family IS110, had the longest non-coding ends of all IS elements. And we started doing experiments in the lab to try to figure out how these work. And what we found was that these elements are cut and paste elements, so they excise themselves into a circular form and paste themselves back in into a target site linearly. But the circularization of this element brings together two distal ends together, which brings together a -35 and a -10 box that create and reconstitute a canonical bacterial transcriptional promoter. This essentially is like plugging a plug into an electrical socket in the wall and it jacks up transcription. Now you would think this transcription would turn on the transposase enzyme so it can jump around more but it transcribes a non-coding RNA out of this non-coding end.(21:30):We're like, holy crap, are these RNAs actually involved in regulating the transposon? Now the boring answer would be, oh, it regulates the expression. It's like an antisense regulate or something. The exciting answer would be, oh, it's a new type of guide RNA and you found an RNA guided integrase. So we started zooming in bound dramatically on this and we undertook a covariation analysis where we were able to show that this cryptic non-coding RNA has a totally novel guide RNA structure, totally distinct from RNAi or CRISPR guide RNAs. And it had a target site that covaried with the target site of the element. And so we're like, oh wow, this could be a programmable transposase. The second thing that we found was even more surprising, there was a second region of complementarity in that same RNA that recognized the donor sequence, which is the circularized element itself. And so, this was the first example of a bispecific guide RNA, and also the first example of RNA guided self-recognition by a mobile genetic element.Eric Topol (22:39):It's pretty extraordinary because basically you did a systematic assessment of jumping genes or transposons and you found that they contain things that previously were not at all recognized. And then you have a way to program these to edit, change the genome without having to do any cuts or nicks, right?Patrick Hsu (23:05):Yeah. So what we showed in a test tube is when we took this, so-called bridge RNA, which we named because it bridges the target and donor together along with the recombinase enzyme. So the two component system, those are the only two things that you need. They're able to cut and paste DNA and recombine them in a test tube without any DNA repair, meaning that it's independent of cellular DNA repair and it does strand nicking, exchange, junction resolution and religation all in a single mechanism. So that's when we got super excited about its potential applications as bioengineering tool.Eric Topol (23:46):Yeah, it's pretty extraordinary. And have you already gone into in vivo assessment?Patrick Hsu (23:54):Yes, in our initial set of papers, what we showed is that these are programmable and functional or recombinases in a test tube and in bacterial cells. And by reprogramming the target and donor the right way, you can use these enzymes not just for insertion, but also for flipping and cutting out DNA. And so, we actually have in a single mechanism the ability to do bridge editing, if you will, for universal DNA recombination, insertion, excision or inversion, similar to what folks have been doing for decades with Cre recombinase, but with fully programmable recognition sequences. The work that we're doing now in the lab as you can imagine is to adapt these into robust tools for mammalian genome editing, including of course, human genomes. We're excited about this, we're making good progress. The CRISPR has had thousands of labs over the last 10, 15 years working on it to make these therapeutic level potency and selectivity. We're going to work and follow that same blueprint for getting bridge systems to get to that level of performance, but we're on the path and we're very optimistic for the future.Exemplar of Digital BiologyEric Topol (25:13):Yeah, I think it's quite extraordinary and it's a whole different look to what we've been seeing in the CRISPR era for over the past decade and how that's been advancing and getting more specific and less need for repair and being able to be more versatile. But this takes it to yet another dimension. Now, this brings me to the field that when I think of this term digital biology, I think of you and now our mutual acquaintance, Jensen Huang, who everybody knows now. Back some months ago, he wrote and said at a conference, “Where do I think the next amazing revolution is going to come? And this is going to be flat out one of the biggest ones ever. There's no question that digital biology is going to be it. For the first time in human history, biology has the opportunity to be engineering, not science.” So can you critique Jensen? Is he right? And tell us how you conceive the field of digital biology.Patrick Hsu (26:20):If you look at gene therapy today, the core concepts are actually remarkably simple. They're elegant. Of course, you're missing a broken gene, you need to put it back. And that can be curative. Very simple, powerful concept. However, for complex diseases where you don't have just a single gene that goes wrong, in many cases we actually have no idea what to do. And in fact, when you're trying to put in DNA, that's over more than a gene scale. We kind of very quickly run out of ideas. Is it a CAR and a cytokine, a CAR and a cytokine and another thing? And then we're kind of out of ideas. And so, we started thinking in the lab, how can we actually design genomes where it's not just let's reduce the genome into individual Lego blocks, iGem style with promoters and different genes that we just sort of shuffle the Lego blocks around, but actually use AI to design genome sequences.(27:29):So to do that, we thought we would have to first of all, train a model that can learn and decode the foreign language of biology and use that in order to design sequences. And so, we sort of have been training DNA foundation models and virtual cell models at Arc, sort of a major effort of ours where the first thing that we tried was to take a variance of transformer architecture that's used to train ChatGPT from OpenAI, but instead apply this to study the next DNA token, right? Now, the interesting thing about next token prediction in English is that you can actually learn a surprising amount of information by just predicting the next word. You can learn world knowledge is the capital of Azerbaijan, is it Baku or is it London, right? Or if you're walking around in the kitchen, then the next text is, I then left the kitchen or the bathroom, right?(28:33):Now you're learning about spatial reasoning, and so you can also learn translation obviously. And so similarly, I think predicting the next token or the next base and DNA can lead you to learn about molecular biochemistry, is the next amino acid residue, hydrophobic or hydrophilic. And it can teach you about the mechanics of some catalytic binding pocket or something. You can learn about a disease mutation. Is the next base, the sick linked base or the wild type base and so on and so forth. And what we found was that at massive scale, DNA foundation models learn about molecular function, not just at the DNA level, but also at the RNA and the protein. And indeed, we could use these to design molecular systems like CRISPR-Cas systems, where you have a protein and the guide RNA. It could also design new DNA transposons, and we could design sequences that look plausibly like real genomes, where we generate a megabase a million bases of continuous genome sequence. And it really looks and feels like it could be a blurry picture of something that you would actually sequence. This has been a wonderful collaboration with Brian Hie, a PI at Stanford and an Arc investigator, and we're really excited about what we've seen in this work because it promises the better performance with even more scale. And so, simply by scaling up these models, by adding in more compute, more training data or more powerful models, they're going to get sharper and sharper.New A.I. Models in Life ScienceEric Topol (30:25):Yeah. Well, this whole use of large language models for the language of life, whether it's the genome proteins and on and on, actually RNA and even cells has really taken root. And of course, this is really one of the foundations of that field of digital biology, which brings together generative AI, AI tools and trying to push forward our understanding in biology. And also, obviously what's been emphasized in drug discovery, perhaps it's been emphasized even too much because we still have a lot to learn about biology, but that gets me to these models. Like today, AlphaProteo was announced by DeepMind, as we all know, AlphaFold 1, 2, now 3. They were kind of precursors of being able to predict proteins from amino acid 3D structure. And that kind of took the field by a little bit like ChatGPT for life science, but now it's a new model all the time. So you've been working on various models and Arc Institute, how do you see this unfolding? Are we just going to have every aspect of the language of life being approached in all the different interactions? And this is going to help us get to a much more deep level of understanding.Patrick Hsu (31:56):I'll say two things. The first is a lot of models that you just described are what I would call task specific models. A model for de novo design of a binder, a model for protein structure prediction. And there are other models for protein fitness or for RNA structure prediction, et cetera, et cetera. And I think what we're going to move towards are more unifying models where there's different classes of models at different levels of scale. So we will have these atomic level models for looking at generative chemistry or ligand docking. We have models that can unify genomes and their molecules, and then we have models that can unify cells and tissues. And so, for example, if you took an H&E stain of some liver, there are folks building models where you can then predict what the single cell spatial transcriptome will look like of that model. And that's obviously operating at a very different level of abstraction than a de novo protein binder. But in the long run, all of these are going to get, I think unified. I think the reason why this is possible is that biology, unlike physics, actually has this unifying theory of evolution that runs across all of its length scales from atomic, molecular, cellular, organismal to entire ecosystem. And the promise of these models is no short then to make biology a predictive discipline.Patrick Hsu (33:37):In physics, the experimentalists win the big prizes for the theorists when they measure gravitational waves or whatever. But in biology, we're very practical people. You do something three times and do a T-test. And I think my prediction is we can actually gauge the success of these LLMs or whatever in biology by how much we respect theory in this field.The A.I. ScientistEric Topol (34:05):Yeah. Well, that's a really interesting perspective, an important perspective because the proliferation of models, which we're going to get into not just doing the things that you described, but also being able to be “pseudo” scientists, the so-called AI scientist. Maybe you could comment about that concept because that's been the idea that everything from the question that could be asked to the hypothesis and the experiment design and the analysis of data and then the feedback. So what is the role of the scientists, that seems to have been overplayed? And maybe you can put that in context.Patrick Hsu (34:48):So yeah, right now there's a lot of excitement that we can use AI agents not just to do software enterprise workflows, but to be a research assistant. And then over time, itself an autonomous research scientist that can read the literature, come up with an idea, maybe run a bunch of robots in the lab or do a bunch of computational analyses and then potentially even analyze data, conclude what is going on and actually write an entire paper. Now, I think the vision of this is compelling in the long term. I think the question is really about timescale. If you break down the scientific method into its constituent parts, like hypothesis generation, doing an experiment, analyzing experiment and iterating, we're clearly going to use AI of some kind at every single step of this cycle. I think different steps will require different levels of maturity. The way that I would liken this is just wet lab automation, folks have dreamed about having pipetting robots that just do their western blots and do their cell culture for them for generations.(36:01):But of course, today they don't actually really feel fundamentally different from the same ones that we had in the 90s, let's say. Right? And so, obviously they're getting better, but it seems to me one of the trends I'm very bullish about is the explosion of humanoid robots and robot foundation models that have a world model and a sense of physics and proportionate space loaded onto them. Within five years, we're going to have home robots that can fold your clothes, that can organize your kitchen and do all of this while you're sleeping, so you wake up to a clean home every day.Eric Topol (36:40):It's not going to be just Roomba anymore. There's going to be a lot more, but it isn't just the hardware, it's also the agents playing in software, right?Patrick Hsu (36:50):It's the integrated loop of the hardware and the software where the ability to make the same machine generally intelligent will make it adaptable to a broad array of tasks. Now, what I'm excited about is those generally intelligent humanoid robots coming into the lab, where instead of creating a centrifuge or a new type of pipetter that's optimized for your Beckman or Hamilton device, instead you just have robot arms that you snap onto the edge of the bench and then they just work alongside you. And I do think that's coming, although it'll take a lot of hardware and software and computer vision engineering to make that possible.A Sense of HumorEric Topol (37:32):Yeah, and I think also going back to originating the question, there still is quite a debate about the creativity and the lack of any simulation of AGI, whatever that means anymore. And so, the human in the loop part of this is obviously I think it's still of critical nature. Now, the other thing I learned about you is you have a great sense of humor, which is really important by the way. And recently, which is great that you're active on X or Twitter because that's one way we get to see what you're thinking on a day-to-day basis. But I think you put out a poll which was really quite provocative , and it was about, here's what it said, “do more people in the world *truly* understand transformers or health insurance?” And interestingly, you got 49% for transformers at 51% for health insurance. Can you tell us what you're thinking when you put that poll together? Because obviously a lot of people don't understand either of these.Patrick Hsu (38:44):I think the core question is, there are different ways of looking at the world, some of which are very bottom up and some of which are very top down. And one of the very surprising things about transformers is they're taking something that is in principle, an incredibly simple task, which is if you have a string of text, what is the next letter? And somehow at massive, massive scale, you can unlock something that looks an awful lot like reasoning, and you've got these emergent behaviors. Now the bottoms up theory of just the linear algebra that's going on in these models couldn't possibly really help us predict that we have these emerging capabilities. And I think similarly in healthcare, there's a literal set of parts that are operating in some complex way that at massive scale becomes this incredibly confusing and dynamic system for how we can actually incentivize how we make medicines, how we actually take care of people, and how we actually pay for any of this from an economic point of view. And so, I think it was, in some sense if transformers can actually be an explainable by just linear algebra equations, maybe there will be a way to decompose the seemingly incredibly confusing world of healthcare in order to actually build a better way forward.Computing Power and the GPU Arms RaceEric Topol (40:12):Yeah. Well that's great. Now the other thing I wanted to ask you about, we open source and the arms race of GPUs and this whole kind of idea is you touched on the need for coalescing a lot of these tools to exploit the synergy. But we have an issue because many academic labs like here at Scripps Research and so many others, including as I learned even at Stanford, have limited access to GPUs. So computing power of large language models is a problem. And then the models that exist today that can be adopted like Llama or others, and they're somewhat limited. And then we also have a movement towards trying to make things more open source, like for example, recently OpenCRISPR with Profluent Bio that is basically trying to use AI for CRISPR guides. And so, how do you deal with this arms race, computing power, open source, proprietary models that are not easily accessible without a lot of resources?Patrick Hsu (41:30):So the first thing I would say is, we are in the academic science sphere really unprepared for the level of resources that are required for doing this type of cutting edge computational work. There are top Stanford computer science professors or computational researchers who have a single GPU in their office, and that's actually what their whole lab runs off of.(41:58):The UC Berkeley campus, the grid runs on something like 12 megawatts of power and how are they going to build an on-premises GPU clusters, like a central question that can scale across the entire needs? And these are two of the top computer science universities in the world. And so, I think one of our kind of core beliefs at Arc is, as science both experimentally and computationally has gotten incredibly complex, not just in terms of conceptually, but also just the actual infrastructure and machines and know-how that you need to do things. We actually need to essentially support this. So we have a private GPU cloud that we use to train our models, and we have access to significantly large clusters for large burst kind of train outs as necessary. And I think infrastructurally for running genomics experiments or doing scalable brain organoid screens, right, we're also building out the infrastructure to support that experimentally.Eric Topol (43:01):Yeah, no, I think this is one of the advantages of the new model like the Arc Institute because not many centers have that type of plasticity with access to computing power when needed. So that's where a brilliant mind you and the Arc Institute together makes for a formidable recipe for future advances and of course building on the ones you've already accomplished.The Primacy of Human TalentPatrick Hsu (43:35):I would just say, my main skill, if I have one, is to recruit really, really smart people. And so, everything that you're seeing and hearing about is the work of unbelievable colleagues who are curious, passionate, and incredible scientists.Eric Topol (43:53):But it also takes the person who can judge those who are in that category set as a role model. And you're certainly doing that. I guess just in closing, I mean, it's just such a delight to get to meet you here and kind of get your thoughts on what is the hottest thing in life science without question, which brings together the fields of AI and what's going on, not just obviously in genome editing, but this digital biology era that we're still in the early phases of, I mean, I think you could say that it's just going to continue to accelerate the exponential curve. We're still kind of on the bottom of that, I would imagine where we're headed. Any other things that you want to bring up that I haven't touched on that will round out this conversation?Patrick Hsu (44:50):I mean, I think it's very early days here at Arc.Patrick Hsu (44:53):When we founded Arc, we asked ourselves, how do we measure success? We don't have customers or revenue in the way that a typical startup does. And we felt sort of three things. The first was research institutes live and die by their talent. Can we actually hire incredible people when we make offers to people we want to come, do they come? The second was, when those folks do come to Arc, do they feel like they're able to work on important research programs that they couldn't do sort of at their prior university or company? And then longer term, the third thing was, and there's just no shortcut around this, you need to do important work. And I think we've been really excited that there are early signs that we're able to do all three of these things, and we're still, again, just following the same scaling laws that we're seeing in natural language and vision, but for the domain of biology. And so, we're excited about what's ahead and think if there are folks who are interested in learning more about Arc, just shoot me an email or DM.Eric Topol (46:07):Yeah, well I would just say, congratulations on what you've already achieved. I know you're going to keep rocking it because you already have in a short time. And for anybody who doesn't know about Arc Institute and your work and your team, I hope this is going to be putting them on notice actually what can be accomplished outside of the usual NIH funded model, which is kind of a risk-free zone where you basically have to have your results nailed down before you send in your proposal frequently, and it doesn't do great things for young people. Really, I think you actually qualify in that demographic where it's hard for them to break in for getting NIH grants and also for this type of work that you're doing. So we'll look for the next bridge beyond bridge RNAs of your just fantastic efforts. So Patrick, thanks so much for joining us today, and we'll be checking back with you and following all the great work that you'll be doing in the times ahead.Patrick Hsu (47:14):Thanks so much, Eric. It was such a pleasure to be here today. Appreciate the opportunity.*******************Thanks for listening, reading or watching!The Ground Truths newsletters and podcasts are all free, open-access, without ads.Please share this post/podcast with your friends and network if you found it informative!Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly help fund our summer internship programs.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff for audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

On October 11, 2024, significant funding rounds occurred, with nine deals exceeding $100 million. Form Energy led these rounds, securing $405 million to enhance its iron-air battery systems. City Therapeutics raised $135 million for RNAi therapeutics in its Series A funding, while EvenUp raised $135 million in Series D funding and achieved a valuation over $1 billion for its AI-based legal tech platform. AtVenu received $130 million to streamline retail sales at live events, and Maven Clinic secured $125 million in its Series F round, focusing on family health and planning. Auger launched with a $100 million seed round for AI-powered supply chain management tools. Cytovale raised $100 million for medical diagnostics, Glooko obtained $100 million for integrated digital health solutions, and Toca Football also secured around $100 million for soccer training centers. Imprint raised $75 million for co-branded credit cards, achieving a $600 million valuation. Internationally, Brazil's Asaas raised approximately $148 million to automate financial processes.Learn more on this news visit us at: https://greyjournal.net/ Hosted on Acast. See acast.com/privacy for more information.

On today's REX Daily Podcast, Dom talks with AgResearch Chief Scientist Dr Axel Heiser about a series of new projects funded by the government's Endeavour Fund, featuring research using technology known as RNAi to control fungal diseases threatening plants and animals, nanofertilisers to reduce pollution from nitrogen loss, and development of new generation biomaterials from protein... He talks with NZ aviation legend Richard Rayward about his early years as a TV cameraman filming deer in the backcountry in the 1960s, setting up Air Safaris in Tekapo and the changing role of agritourism in NZ... And he talks with Rochelle Flint, chief brand and product officer of Bremworth, about screening the country's first complete TV commercial made by artificial intelligence (AI). Tune in daily for the latest and greatest REX rural content on your favourite streaming platform, visit rexonline.co.nz and follow us on Instagram, Facebook and LinkedIn for more.

In this episode, Ayesha spoke with Kirk Brown, PhD, Vice President of Research at Alnylam Pharmaceuticals. Alnylam is focused on developing RNAi medicines to transform the way diseases like cardiovascular and neurological diseases are treated. Dr. Brown's preclinical work combining stable siRNA designs with alternative conjugation strategies has enabled potent, long-lasting silencing across the CNS following a single intrathecal administration.  In addition to driving RNAi platform innovations, Dr. Brown leads a team of CNS target biologists at Alnylam and serves as the research lead for ALN-APP, the first clinical CNS RNAi program. In this episode, Dr. Brown discusses the promise and evolving landscape of RNAi therapeutics across various therapeutic areas and Alnylam's approach to developing innovative RNAi medicines. For more life science and medical device content, visit the Xtalks Vitals homepage. https://xtalks.com/vitals/ Follow Us on Social Media Twitter: https://twitter.com/Xtalks Instagram: https://www.instagram.com/xtalks/ Facebook: https://www.facebook.com/Xtalks.Webinars/ LinkedIn: https://www.linkedin.com/company/xtalks-webconferences YouTube: https://www.youtube.com/c/XtalksWebinars/featured

Corn growers in eastern Canada have a new tool in their pest management toolbox with the registration of VT4PRO with RNAi technology from Bayer Crop Science. The company says the trait will deliver the latest in corn rootworm defence, with above-ground control and effective root protection, providing a broad spectrum of defence for growers against... Read More

Jay and Ashley share their corn rootworm observations from the growing season. Interesting with above average rainfall to their west, and new experience with the western variant to the east.

On this week's MyAgLife in Technology episode, Oregon State's Surendra Dara details his upcoming Crop Consultant Conference session on RNA interference technology as a new tool for biological pest management.    Supporting the People who Support Agriculture Thank you to this month's sponsors who makes it possible to get you your daily news. Please feel free to visit their website. New Age Ag Services - https://www.newageagservices.com/ 2024 Crop Consultant Conference - https://progressivecrop.com/conference/

Discover the cutting-edge world of RNA interference (RNAi) therapeutics with Dr. Akshay Vaishnaw, Chief Innovation Officer at Alnylam Pharmaceuticals. In this episode, Dr. Vaishnaw sheds light on the groundbreaking concept of RNAi therapeutics, offering a powerful new approach to treating a wide range of diseases. Learn how Alnylam Pharmaceuticals is revolutionizing healthcare with its unwavering commitment to innovation, despite facing numerous setbacks and challenges along the way.

BestPodcastintheMetaverse.com Canary Cry News Talk #756 07.10.2024 - Recorded Live to 1s and 0s BORDER RUSE | Biden Bashing, Bird Flu Con, RNAi, Nephilim Update Deconstructing Corporate Mainstream Media News from a Biblical Worldview Declaring Jesus as Lord amidst the Fifth Generation War! TJT Youtube (backup) Channel: https://www.youtube.com/@TheJoyspiracyTheory The Show Operates on the Value 4 Value Model: http://CanaryCry.Support Join the Supply Drop: https://CanaryCrySupplyDrop.com                   Submit Articles: https://CanaryCry.Report Submit Art: https://CanaryCry.Art Join the T-Shirt Council: https://CanaryCryTShirtCouncil.com Podcasting 2.0: https://PodcastIndex.org Resource: Index of MSM Ownership (Harvard.edu) Resource: Aliens Demons Doc (feat. Dr. Heiser, Unseen Realm) Resource: False Christ: Will the Antichrist Claim to be the Jewish Messiah Tree of Links: https://CanaryCry.Party All Producers of 756 will be thanked on the next CCNT Episode!  SHOW NOTES/TIMESTAMPS Podcast T- 05:55 PreShow Prayer: Anthony H 06:05 V / 00:10 P HELLO, RUN DOWN 09:59 V / 04:04 P   WW3 12:09 V / 06:14 P Poland must prepare army for full-scale conflict, army chief says (VOA) → Poland will do what is needed to end Belarus border crisis (Reuters)   HARRY LEGS 23:39 V / 17:44 P Clip: Intellectual Wigger Clip: Joe was “talking” his wife? Clip: Jake Tapper demolishing Joe Biden speech like the right used to (CNN/X)   Biden didn't show up for an early evening meeting with the German chancellor because he had to go to bed: report (Insider)    VALUE FOR VALUE FOR THE WIN! 44:12 V / 38:12 P   FLIPPY 53:31 V / 47:36 P Is the Annin AR4 the Workhorse Robot Arm for You? (Hacksters.io)   BIRD FLU 01:02:45 V / 56:50 P International Bird Flu Preparedness Conference in October (Bird Flu Summit) → From Kamboree (X)   CRISPR 01:17:54 V / 01:11:59 P Move over, CRISPR: Jumping gene found in humans acts as a bridge between bits of DNA (GLP)   V4V/TALENT    NEPHILIM UPDATE 01:26:07 V / 01:20:12 P Cops rescue terrified teens from 'growling Bigfoot with glowing eyes' in Louisiana forest - amid spate of sightings (DailyMail)    → Terrified teens spot ‘Bigfoot' with ‘glowing eyes' in Louisiana forest, call 911 for rescue (NY Post)  OUTRO 01:36:35 V / 01:30:40 P END 01:47:16 V / 01:41:21 P

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Taylor Chalstrom sits down with Surendra Dara, entomologist with Oregon State University, to discuss RNAi, a new technology using targeted mechanisms against specific pests.

Today we have lots of live comments and feedback from the audience… (6:06) We look at actual questions between Supreme Court & Trump's lawyer, and I have a few of my own…Does a President have legal immunity if he assassinates his political enemies or is that only for the CIA?If he kills millions with a toxic genetic code injection, is it only BigPharma that gets legal immunity or does the President also get it in "his official capacity"?If he overthrows the government with Exec Orders and fake emergencies is that "insurrection" or is insurrection a protest against his opponentIf the President does it, is it against the law? (Asking for Nixon)(22:56) In this Game of Thrones, winning at the Supreme Court doesn't matter. THIS is the only thing that matters… (35:51) NYT Sensational Panic Headline — Then Article Walks Dismisses.  Why?Fear, Panic, Nudge —> Surveillance, Mass Vaccination, and ultimately ELIMINATION of DAIRY & MEAT (as they've been boasting they'll do)WATCH Inventor of PCR explains the fraud — HOW MANY TIMES WILL PUBLIC FALL FOR IT?(54:38) It's Looking Like 2020…Says A Key Player Behind "Pandemic" Fraud (1:12:25) Biden just signed on to a new Bill Gates funded pandemic surveillance plan — the Pandemic Fund (1:25:58) Universal Vaccine — Mutate & Sterilize "Virus" with RNAi, Not mRNA What could possibly go wrong?  They tell us it's effective on EVERY virus (easily tweaked) and perfectly safe.  The very description of its operation is pure madness (1:33:05) Reminder, like so many others, Herman Cain died on (from?) ventilator (1:34:38) Why and how DNA fragments (left by the BILLIONS in each shot) cause cancer FDA partnered with Moderna & Pfizer to cover up the crime and give the corporations legal immunity (1:49:56) Harvard psychologist with ties to BigPharma pushes SSRI (murder/suicide pills) to be dispensed over-the-counter without prescription! (2:02:37)WHO warns of coming 77% increase of cancer…not the jab they sayWhat the EUA (Emergency Use Authorization) is and IS NOT.  Government moves were carefully calculated to legally protect themselves (after they created the laws)(2:14:37) Biden's EPA drops 4 new "rules" to destroy the power grid  (And fuel is racist says head of EPA) (2:25:57) Peer-Reviewed Study & Nobel Scientists Say CO2 CANNOT Cause Climate Change The reason is very simple, actually (2:48:00) Biden & mainstream media keep fighting to destroy Parental Rights and children's bodies.  Biden revives Obama Dept of Eduction money lever to get boys in girls showers and bathrooms and the old sniffer adds some new things.  DeSantis says they will not comply but…Find out more about the show and where you can watch it at TheDavidKnightShow.comIf you would like to support the show and our family please consider subscribing monthly here: SubscribeStar https://www.subscribestar.com/the-david-knight-showOr you can send a donation throughMail: David Knight POB 994 Kodak, TN 37764Zelle: @DavidKnightShow@protonmail.comCash App at: $davidknightshowBTC to: bc1qkuec29hkuye4xse9unh7nptvu3y9qmv24vanh7Money is only what YOU hold: Go to DavidKnight.gold for great deals on physical gold/silverFor 10% off Gerald Celente's prescient Trends Journal, go to TrendsJournal.com and enter the code KNIGHT

Today we have lots of live comments and feedback from the audience… (6:06) We look at actual questions between Supreme Court & Trump's lawyer, and I have a few of my own…Does a President have legal immunity if he assassinates his political enemies or is that only for the CIA?If he kills millions with a toxic genetic code injection, is it only BigPharma that gets legal immunity or does the President also get it in "his official capacity"?If he overthrows the government with Exec Orders and fake emergencies is that "insurrection" or is insurrection a protest against his opponentIf the President does it, is it against the law? (Asking for Nixon)(22:56) In this Game of Thrones, winning at the Supreme Court doesn't matter. THIS is the only thing that matters… (35:51) NYT Sensational Panic Headline — Then Article Walks Dismisses.  Why?Fear, Panic, Nudge —> Surveillance, Mass Vaccination, and ultimately ELIMINATION of DAIRY & MEAT (as they've been boasting they'll do)WATCH Inventor of PCR explains the fraud — HOW MANY TIMES WILL PUBLIC FALL FOR IT?(54:38) It's Looking Like 2020…Says A Key Player Behind "Pandemic" Fraud (1:12:25) Biden just signed on to a new Bill Gates funded pandemic surveillance plan — the Pandemic Fund (1:25:58) Universal Vaccine — Mutate & Sterilize "Virus" with RNAi, Not mRNA What could possibly go wrong?  They tell us it's effective on EVERY virus (easily tweaked) and perfectly safe.  The very description of its operation is pure madness (1:33:05) Reminder, like so many others, Herman Cain died on (from?) ventilator (1:34:38) Why and how DNA fragments (left by the BILLIONS in each shot) cause cancer FDA partnered with Moderna & Pfizer to cover up the crime and give the corporations legal immunity (1:49:56) Harvard psychologist with ties to BigPharma pushes SSRI (murder/suicide pills) to be dispensed over-the-counter without prescription! (2:02:37)WHO warns of coming 77% increase of cancer…not the jab they sayWhat the EUA (Emergency Use Authorization) is and IS NOT.  Government moves were carefully calculated to legally protect themselves (after they created the laws)(2:14:37) Biden's EPA drops 4 new "rules" to destroy the power grid  (And fuel is racist says head of EPA) (2:25:57) Peer-Reviewed Study & Nobel Scientists Say CO2 CANNOT Cause Climate Change The reason is very simple, actually (2:48:00) Biden & mainstream media keep fighting to destroy Parental Rights and children's bodies.  Biden revives Obama Dept of Eduction money lever to get boys in girls showers and bathrooms and the old sniffer adds some new things.  DeSantis says they will not comply but…Find out more about the show and where you can watch it at TheDavidKnightShow.comIf you would like to support the show and our family please consider subscribing monthly here: SubscribeStar https://www.subscribestar.com/the-david-knight-showOr you can send a donation throughMail: David Knight POB 994 Kodak, TN 37764Zelle: @DavidKnightShow@protonmail.comCash App at: $davidknightshowBTC to: bc1qkuec29hkuye4xse9unh7nptvu3y9qmv24vanh7Money is only what YOU hold: Go to DavidKnight.gold for great deals on physical gold/silverFor 10% off Gerald Celente's prescient Trends Journal, go to TrendsJournal.com and enter the code KNIGHT

Editor's Summary by Christopher W. Seymour, MD, MSc, Associate Editor of JAMA, the Journal of the American Medical Association, for the March 5, 2024, issue.

Conviértete en un seguidor de este podcast: https://www.spreaker.com/podcast/marketing-digital--2659763/support.Encuentra a Toni Pérez en https://www.toniperezrealtor.com/Toni Pérez es agente inmobiliario con más de 18 años de experiencia en el sector. Como CEO de Unika Realty, una destacada agencia de producto residencial en las provincias de Girona y Barcelona, se enorgullece ofrecer un servicio excepcional en la compra y venta de propiedades. Además, como CEO de Patricia Emerald, una reconocida marca especializada en la gestión de propiedades de lujo, se dedica a ayudar a sus clientes a encontrar verdaderas joyas inmobiliarias. Su enfoque se centra en propiedades singulares como castillos, palacios, bodegas y otras exclusivas oportunidades de inversión, como hoteles, edificios y geriátricos, tanto en España como en Andorra. Con el fin de brindar un servicio de calidad y mantenerse actualizado en las últimas tendencias del mercado inmobiliario, es miembro de prestigiosas organizaciones como CRS, REALTOR y formo parte de Agora MLS, Agora Luxury, Fiabci, RNAI e Immosomni.Además, como miembro de Trivion, tiene el privilegio de compartir su conocimiento y experiencia como formador inmobiliario, y forma parte de AEPSI como Personal Shopper Inmobiliario. Preguntas en el podcast: Quién eresTu mayor éxitoTu mayor fracasoInversión en sector inmobiliarioSi empezaras de cero qué haríasCasa de lujo: Cómo vender si no se pueden anunciarNuevos proyectosClub inmobiliarioEstrategia de ventas con contactos por WhatsAppCómo conseguir conectores que te traigan clientesComisionesProductividadCuánto tiempo se tarda en vender un castilloAcceso al Club Inmobiliario: https://chat.whatsapp.com/D8Vg9KIbVmK8OJzIgEFlTu Más sobre Borja Girón:Únete al club de emprendedores: https://borjagiron.com/comunidadÚnete a la Newsletter Privada: https://borjagiron.com/newsletterMasterclass “Secretos de Productividad”: https://borjagiron.com/secretos-productividad/Masterclass “Deja de Procrastinar”: https://borjagiron.com/dejar-de-procrastinar/¿Eres Community Manager, Asistente Virtual o Trafficker y estás buscando clientes de calidad que valoren tu trabajo?: https://borjagiron.com/clientes/Secretos para emprender (landing page optimizada con nueva estrategia): https://borjagiron.com/secretos-emprender-exito/Sigue el canal de Audios Privados Emprendedores en WhatsApp: https://whatsapp.com/channel/0029VaCvyBXEFeXtKEBJxy3v

In this episode, Dr. Mithila Jugulam, a professor at Kansas State University provides an in-depth exploration of herbicide resistance, the impact of environmental factors such as elevated temperatures on herbicide effectiveness, and the development of herbicide tolerance in crops. With a focus on solutions to address weed management challenges in the crop industry, this episode offers invaluable insights into crop protection. Join us as we explore the cutting-edge research that is shaping the crop industry's future and ensuring sustainable agriculture practices."While herbicide resistance is such a challenge for weed management, having herbicide-tolerant traits in crops is highly beneficial for growers."What you'll learn:(00:00) Highlight(01:05) Introduction(04:17) Insights into weed resistance to herbicides(06:41) Herbicide tolerance in crops(14:05) The effect of temperature on herbicide efficacy(22:55) Innovative research on glyphosate resistance mechanisms(28:15) RNA interference (RNAi) technology in weed management(31:27) Final Three QuestionsMeet the guest: Dr. Mithila Jugulam, a professor at Kansas State University, specializes in weed physiology with a focus on the complexities of herbicide resistance. Her research explores the mechanisms of herbicide resistance in weeds, encompassing environmental influences on herbicide effectiveness and pioneering strategies for enhancing crop resilience. Dr. Jugulam has been at the forefront of agricultural science, contributing significantly to our understanding of weed management and crop protection. Her work addresses current challenges in the crop industry and lays the groundwork for future advancements in agriculture.The Crop Science Podcast Show is trusted and supported by innovative companies like:- KWSAre you ready to unleash the podcasting potential of your company? wisenetix.co/custom-podcast

פרופ׳ יניב ארליך, מי שהיה המדען ראשי של חברת MyHeritage ופרופסור למדעי המחשב באוניברסיטת קולומביה, מוביל את חברת Eleven Therapeutics, שמנסה לעשות מהפכה בכל הנוגע לפיתוח תרופות וחיסונים בשיטת ה-RNAi. דיברנו על תרופות הרזיה, פיתוחים מתקדמים בביולוגיה ושלל נושאים אחרים.   נותני החסות לפרק: הפרק בחסות חברת Cato Networks הפרק עם עידן מקייטו נטוורקס

In this episode of The 92 Report, Peter Kang attended medical school in Philadelphia where he had a wonderful experience at the University of Pennsylvania, learning about different fields and cultures, and making friends. One pivotal moment in medical school was during a physician patient relationship course led by a thoughtful psychiatrist who reminded him that it's a routine experience for the doctors, but it could be one of the most pivotal moments in the patient's life, and they can remember everything about their encounters, which has been helpful to him throughout his career. A Career in Pediatric Neurology Peter chose pediatric neurology as his field of study, completing most of his training in Philadelphia and New Haven. He spent over a decade in Boston, where he gained valuable exposure to both the Boston area and New England. His mentorship from a well-known geneticist, Luke Konkel, helped fill a crucial gap in his career as a physician scientist. This experience gave him a strong background in genetics and has been useful to him up to this day. Peter's research interests include rare diseases. In his clinic work, he deals with these patients daily, as they might be one of only a few dozen people in the United States with that particular diagnosis. The challenge is finding enough patients to prove that a treatment works or an idea about the disease is valid. Peter also runs a research laboratory and spends much of his time supervising the lab. However, he finds it both interesting and useful to be able to connect his work in the lab with his work in the clinic.  Genomics Research and Genetic Diseases Peter discusses his experience running a research lab and how it has evolved over the years. He started his independent research laboratory in Boston and later moved to Florida in 2013. He learned about running a lab from his mentor, which involved a lot of subtleties and was a lot like running a small business in terms of financing, grant applications, and hiring and managing personnel etc. The lab's focus is on genomics research, which helps identify patients with genetic diseases that don't have clear diagnoses. He explains some of the difficulties they run into and how they approach mystery diagnosis.Peter is currently a professor at the University of Minnesota, where his lab is based. He moved to Minnesota during the COVID pandemic. He and his wife were initially excited about moving to Minnesota.The move was motivated by the opportunity to work with a renowned muscular dystrophy center at the University of Minnesota, which had a unique focus on the condition.  Finding Solutions to Mystery Diagnosis Peter's lab has been working on finding solutions to mystery diagnosis in genetic testing, which has been a focus for over a decade. He believes that genetic testing can help solve these mysteries and is working towards a more accurate understanding of genetic diseases. Peter discusses the challenges of treating rare neurological diseases, particularly in children. He highlights two types of diseases that have been challenging to diagnose and treat: muscular dystrophy and spinal muscular atrophy. Muscular dystrophy is a childhood disease, with milder forms starting in adulthood. Duchenne muscular dystrophy is a well-known example, with patients often experiencing difficulty walking and falling as they grow older. Genetic testing has become more effective in diagnosing these diseases, but there are still shortened life expectancies and increased dependence on others for activities. Spinal muscular atrophy is another type of disease that is not technically classified as muscular dystrophy but is also seen in neuromuscular specialists. The most severe form of this disease was typically fatal by the age of two years due to motor neuron loss in the spinal cord. However, in 2016, the first FDA treatment for spinal muscular atrophy was approved, which has helped children to walk normally and avoid ventilators. Screening Programs and Metabolic Disorders Peter talks about the newborn screening programs that have been around for several decades, with each state offering slightly different panels of tests. The original screening tests focused on metabolic disorders, which could be treated by eliminating certain nutrients from the baby's diet. Newborn screening has evolved to include spinal muscular atrophy and genetically based tests. Some metabolic disorder diseases have been cured now, with some being cured through diet changes and new therapies being developed. However, Peter highlights the fact that the exact cure depends on how the word "cure" is applied, which is a topic of discussion among inpatient communities. Overall, he emphasizes the importance of early detection and treatment for rare neurological diseases to improve outcomes and overall health. Peter discusses his experiences dealing with pediatric patients and how he is constantly developing his interaction skills. He emphasizes the importance of understanding the patient's perspective and avoiding taking sides. He also shares his experience of dealing with multiple people in the room, including parents and spouses, and how to navigate these conversations effectively. Challenges in Pediatric Medicine One challenge in pediatric medicine is dealing with multiple people, and sometimes there may be a difference of opinion between the child and their parent. To address this, he suggests documenting both sides of the medical record and discussing the perspectives of both parties. When discussing a child with muscular dystrophy, he advises communicating the diagnosis to the parents and the child, considering their age and preferences. He also advises being candid about the prognosis and focusing on the positives. He does not spontaneously discuss life expectancy during clinic visits due to its unpredictable nature and the hope that new therapies will come online for these patients. Advances in Biotechnology Peter talks about advancements in biotechnology. In the past few years, there has been an inflection point in biotech with advancements like RNAi, Moderna, and other technologies. There is an incredible array of technologies available that were not available in the past, such as small molecules, gene therapies, stem cells, and proteins. The interaction between academia and the biotech industry has become more collaborative, and there is a better understanding that they are working towards the same goals. Peter states that, in the future, there will be more genetic or molecular solutions specific to certain targets for treating both rare and common diseases. This specificity will continue to grow, and there will be ways to accelerate the pace of developing tailored treatments. Harvard Courses and Professors on Influence Peter mentions two gratifying courses that still resonate with him today. One was Philosophy 168, taught by John Rawls, which helped him understand Kant's ethical theory and how to see things from a different perspective. Another course was Expository Writing 52, taught by Richard Marius, who showed him how powerful writing could be and how words can influence people's behavior. Peter believes these courses have helped him develop confidence in his writing abilities and have prepared him for the challenges of personalized medicine in the coming decades. He is looking forward to the developments in the biotech sector and the potential for personalized medicine to become more of a reality. He recalls a conversation with Richard Marius, who encouraged him to bring the story to life and that it's okay to write about one's family. He also discusses how his education as a philosopher major has helped him with thinking and analysis, and achieving clarity around a particular issue or ethical dilemma. He uses this knowledge to resolve complex issues and helps patients make informed decisions about therapy options. On a global scale, Peter addresses the resource allocation for Rare Disease Research, which is a thorny problem due to limited resources. He believes that it's crucial to not let individuals with rare diseases be left behind, as they often feel isolated and struggle to find others who understand their condition.  Timestamps: 04:20 Rare disease research and clinical practice 08:52 Running a research lab, genomics research, and mystery diagnoses 14:03 Muscular dystrophy diagnosis and treatment 20:00 Treating and curing neuromuscular diseases in children 28:26 Communicating with children about serious illnesses 32:57 Rare disease diagnosis and potential treatments 38:13 Personalized medicine, gene editing, and philosophy 43:00 Writing skills, ethical dilemmas, and rare diseases CONTACT: https://med.umn.edu/bio/peter-b-kang https://www.linkedin.com/in/pbkang pbkang@post.harvard.edu  

This week, listeners are in for a real treat as I sit down with Dr. Meibao Zhuang, Senior Scientist/Regulatory Consultant with B&C and our consulting affiliate, The Acta Group, to discuss double-stranded ribonucleic acid interference, better known as ds RNAi. Ds RNAi is a technology that allows scientists to silence (or interfere with) a particular gene. In the agricultural sector, this genetic modification can be used to great advantage to control pests of all sorts with extreme precision. Meibao will discuss EPA's proposed registration of the first sprayable RNAi biopesticide and the exciting implications of this technology. ALL MATERIALS IN THIS PODCAST ARE PROVIDED SOLELY FOR INFORMATIONAL  AND ENTERTAINMENT PURPOSES. THE MATERIALS ARE NOT INTENDED TO CONSTITUTE LEGAL ADVICE OR THE PROVISION OF LEGAL SERVICES. ALL LEGAL QUESTIONS SHOULD BE ANSWERED DIRECTLY BY A LICENSED ATTORNEY PRACTICING IN THE APPLICABLE AREA OF LAW. ©2023 Bergeson & Campbell, P.C.  All Rights Reserved

Even under the best conditions, crops need our assistance to survive the numerous threats that limit production. Classically, synthetic and natural compounds have been used to control insects, fungi and weeds, sometimes with negative collateral effects or fostering resistance of genetically tolerant genotypes. Todd Hauser from Trillium Ag describes his company's novel RNAi approach.  RNAi can be used to target specific insect species, and his company's design and particle-based technology appears to offer safety, effectiveness, and specificity. We discuss the use of RNAi and how it may be a key point of crop protection strategies, along with its inherent challenges.  

This week on North American Ag Spotlight Chrissy Wozniak learns about RNAi technology in agriculture from Todd Hauser, the Co-founder and Chief Executive Officer of Trillium Ag.  With more than 20 years of experience in biotechnology and gene silencing, Todd is a leader in the movement to modernize crop protection.  With an expert understanding of crop science and a passion to protect the long-term global food supply and the environment, Todd brings a unique combination of scientific experience and technological knowledge to Trillium Ag.Trillium Ag (www.trillium.ag) was founded in 2016 by Todd Hauser and Paul Olivier, two Seattle-area scientists and entrepreneurs with a more then 50 years of combined experience in bio-technology and RNA Interference (RNAi).  Their goal was to unlock the potential for a safer and more sustainable approach to farming by creating a revolutionary new class of biologicals that target pests and provide superior crop protection.  Leveraging their scientific expertise and new developments in RNAi technology, Trillium's co-founders recognized an opportunity to develop a crop protection platform that is greener, more effective and provides the answer to agriculture's escalating pest problem.      Traditional approaches to crop protection, such as synthetic chemicals and bacterial toxins, are in rapid decline. Due to increasing pest resistance, as well as regulatory and consumer pressures, there is an urgent need for new crop protection strategies in order to avoid continued worldwide crop losses of $220 billion annually.  The Trillium Ag team understood that the agricultural industry was facing a growing problem and it was critical to uncover a solution in order to secure the world's long-term food supply.  Tapping cutting-edge science and modern technology, Trillium Ag has developed Agrisome, the future of crop protection.Trillum Ag's patented Agrisome technology is a revolutionary crop protection platform that employs first-of-its-kind biologicals to target agriculture's most problematic pests, including, but not limited to, the lepidoptera and hemiptera insect classes.  Alone, these two orders of insects are responsible for $50 billion in crop losses across the globe annually.  Leveraging innovative RNAi science, Trillium Ag's breakthrough platform delivers a scalable, adaptable and stacked line of crop defense, providing a sustainable and biodegradable solution in the fight against crop-targeting pests. Agrisome utilizes naturally-derived protein coated RNA molecules creating a new class of biologicals that address and solve challenges that have hindered prior RNAi-derived crop protection attempts.  Agrisome targets and activates a pests own naturally occurring processes through gene silencing, unlocking a safer and more sustainable approach to farming.  Offering a topical and seed trait based product platform, Agrisome serves as a replacement for synthetic chemical pesticides and is poised to transform the agricultural industry. Agrisome has proven efficacy in both in vitro and in vivo models and Trillium Ag is currently collaborating with the industry's top commercial and academic leaders to further confirm commercial feasibility and broad scale agricultural application.  In addition, Trillium Ag's pipeline, which is based on naturally-derived protein coated RNA molecules, includes added sustainable bio-agriculture products currently in the research and development stage.Learn more about Trillium Ag at https://trillium.ag#rnai #modernfarming #agricultureNeed help with your agriculture based company's marketing plan? https://www.northamericanag.com/full-service-agri-marketingDon't just thank a farmer, pray for one too!Subscribe today at NorthAmericanAg.com!Subscribe to North American Ag at https://northamericanag.com

Dr. Steven Quay is the founder of Seattle-based Atossa Therapeutics Inc., established in 2009. Prior to his work at Atossa, he served as Chairman of the Board, President and Chief Executive Officer of MDRNA, Inc., a biotechnology company focused on the development and commercialization of RNAi-based therapeutic products, from August 2000 to May 2008, and as its Chief Scientific Officer until November 30, 2008 (MDRNA, Inc. was formerly known as Nastech Pharmaceutical Company Inc. and is currently known as Marina Biotech, Inc.). Dr. Quay is certified in Anatomic Pathology with the American Board of Pathology, completed both an internship and residency in anatomic pathology at Massachusetts General Hospital, a Harvard Medical School teaching hospital, and is a former faculty member of the Department of Pathology, Stanford University School of Medicine.   Dr. Quay is a named inventor on 76 U.S. patents, 108 pending patent applications and is a named inventor on patents covering five pharmaceutical products that have been approved by the U.S. Food and Drug Administration. He received an M.D. in 1977 and a Ph.D. in 1975 from the University of Michigan Medical School. He also received his B.A. degree in biology, chemistry and mathematics from Western Michigan University in 1971. Dr. Quay is a member of the American Society of Investigative Pathology, the Association of Molecular Pathology, the Society for Laboratory Automation and Screening and the Association of Pathology Informatics.

Genetic Testing and Stone Disease Co-host: Kyle Wood, MD Population analysis demonstrated that genetic conditions resulting in stone disease are magnitudes higher than those seen in clinical cohorts, suggesting underdiagnosis. Urologist play a unique role as we often times have many touch points with these patient given their presentation for stone disease. With the advancement of treatments, specifically in primary hyperoxaluria, it is essential that urologist play a more active role in the earlier diagnosis of patients. Genetic testing has become readily available at lower cost and much of the perceived barriers to genetic testing are addressed by current available programs. Outline: 1. The contribution of genetics to kidney stone disease 2. Specific studies using genetic testing 3. Primary Hyperoxaluria as an example 4. Current Genetic Testing and Ease 5. The role of the Urologist References: - Hill AJ, Basourakos SP, Lewicki P, et al. Incidence of kidney stones in the United States: The Continuous National Health and Nutrition Examination Survey. J Urol. 2022;207(4):851-856. - Singh P, Harris PC, Sas DJ, Lieske JC. The genetics of kidney stone disease and nephrocalcinosis. Nat Rev Nephrol. 2022;18(4):224-240. - Goldfarb DS, Fischer ME, Keich Y, Goldberg J. A twin study of genetic and dietary influences on nephrolithiasis: a report from the Vietnam Era Twin (VET) Registry. Kidney Int. 2005;67(3):1053-1061. - Daga A, Majmundar AJ, Braun DA, et al. Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis. Kidney Int. 2018;93(1):204-213. - Braun DA, Lawson JA, Gee HY, et al. Prevalence of monogenic causes in pediatric patients with nephrolithiasis or nephrocalcinosis. Clin J Am Soc Nephrol. 2016;11(4):664-672. - Halbritter J, Baum M, Hynes AM, et al. Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis. J Am Soc Nephrol. 2015;26(3):543-551. - Knoers N, Antignac C, Bergmann C, et al. Genetic testing in the diagnosis of chronic kidney disease: recommendations for clinical practice. Nephrol Dial Transplant. 2022;37(2):239-254. - Groothoff JW, Metry E, Deesker L, et al. Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope. Nat Rev Nephrol. 2023;19(3):194-211. - van der Hoeven SM, van Woerden CS, Groothoff JW. Primary hyperoxaluria type 1, a too often missed diagnosis and potentially treatable cause of end-stage renal disease in adults: results of the Dutch cohort. Nephrol Dial Transplant. 2012;27(10):3855-3862. - Hopp K, Cogal AG, Bergstralh EJ, et al. Phenotype-genotype correlations and estimated carrier frequencies of primary hyperoxaluria. J Am Soc Nephrol. 2015;26(10):2559-2570. - Garrelfs SF, Frishberg Y, Hulton SA, et al. Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1. N Engl J Med. 2021;384(13):1216-1226. - Baum MA, Langman C, Cochat P, et al. PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2. Kidney Int. 2023;103(1):207-217. - Soliman NA, Nabhan MM, Abdelrahman SM, et al. Clinical spectrum of primary hyperoxaluria type 1: Experience of a tertiary center. Nephrol Ther. 2017;13(3):176-182. - Schonauer R, Scherer L, Nemitz-Kliemchen M, et al. Systematic assessment of monogenic etiology in adult-onset kidney stone formers undergoing urological intervention-evidence for genetic pretest probability. Am J Med Genet C Semin Med Genet. 2022;190(3):279-288.

BUFFALO, NY- October 3, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on September 25, 2023, entitled, “DISE, an ancient anti-cancer mechanism that senses mutational load in cancerous cells?” In their new editorial, researchers Monal Patel and Marcus E. Peter from Northwestern University discuss a recent breakthrough in cancer therapy. Despite the multiple advances in therapy, cancer remains one of the most common causes of death globally. It is a systemic disease affecting people of all ages and originates at the level of single cells which, upon acquisition of mutations, become neo-plastically transformed. Cell division is the biggest risk factor for the accumulation of mutations, explaining why all multicellular organisms which evolved about 2 billion years ago, are prone to cancer. Given the recent achievements in cancer treatment with immune checkpoint blockade therapies, multicellular organisms may have developed the immune system as a mechanism to eradicate cancerous cells. “However, the immune system arose relatively recent, ~500 million years ago [3].” Moreover, studies have shown that cancer cells can become resistant to the anticancer activity of both the innate and the adaptive immune system. Therefore, while the immune system is important, it is likely not the most vital machinery that emerged in multicellular organisms to prevent cancer formation. The researchers believe that there are other more effective and archaic anti-cancer mechanisms that are conserved during evolution. Of note, RNA interference (RNAi) is a highly conserved biological mechanism for silencing gene expression. While RNAi likely emerged as a defense tool against viruses and other foreign nucleic acids, it has also evolved to have other activities in the cells. The team's research has identified a new evolutionarily conserved RNAi-based form of cell death that targets essential survival genes: Death Induced by Survival gene Elimination (DISE). “DISE was discovered through our work on CD95 and its ligand, CD95L, where we found that more than 80% of 26 different short interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) derived from the two genes, killed multiple cancer cell lines via simultaneous activation of multiple cell death pathways; and we were unable to find a way to inhibit this form of cell death [9].” DOI - https://doi.org/10.18632/oncotarget.28466 Correspondence to - Marcus E. Peter - m-peter@northwestern.edu Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28466 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, cell death, evolution, RNAi, short RNAs About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Pests, such as corn rootworm, continue to evolve and so does the technology required to control these these yield-robbing insects. At Canada’s Outdoor Farm Show earlier this month, Bayer Crop Science launched SmartStax Pro with RNAi technology, a new mode of action to help defend corn plants against the pest. David Kikkert, Bayer Crop Science’s... Read More

The next generation of rootworm control is set to hit Ontario fields in 2024. Developed through RNAi technology, PRIDE Seeds SmartStax Pro rootworm control G9 corn hybrids offers a three-pronged attack for control of this yield robber. Matt Chapple, product development manager with PRIDE Seeds, says this new trait will offer a third mode of... Read More

In today's episode, Rachel Ford Hutman and I talk through her journey in media relations, starting Ford Hutman Media and thriving through brand awareness in the life sciences space. Rachel Ford Hutman is the Founder and CEO of Ford Hutman Media. With 15+ years of communications experience at leading global PR agencies and a senior comms role at IBM, she created the agency to provide industry-leading media relations and thought leadership to elite life science companies across the globe. Clients range from venture-backed startups to large cap public companies. Rachel started her career as a reporter and excels at working with the media to bring life science stories to life while still making them accessible to stakeholders.During her career, Rachel has led communications for the world's biggest therapies and medical technologies of all time, including the first RNAi therapy (Alnylam's ONPATTRO), the first technology in the world to personalize insulin 24 hrs. a day (Medtronic's MiniMed 670G), IBM's AI launch into healthcare (Watson Health), the first therapy for DMD (Sarepta's EXONDYS 51), and Google's sister life science company (Verily). She has counseled some of the most well-known health/ technology organizations and developed communications strategies for the world's biggest brands (Verily, Johnson & Johnson, Medtronic, Pfizer, IBM, Best Buy, Takeda, Sanofi, Shire, Brigham & Women's, NHS).Rachel is consistently leveraging her long-standing relationships with global agenda-setting reporters on behalf of clients including CNBC, FOX Business, BBC, AP, Reuters, Bloomberg, The Today Show, Newsweek, Financial Times, Fast Company, TIME, Wired, Forbes, WSJ, NYTs, and key health trades like Modern Healthcare, Becker's Hospital Review, Digital Health Journal, GenomeWeb, BioWorld, Tech Republic, FierceBiotech, Endpoints, Drug Discovery Today and many more. Rachel also has investor and analyst relations experience that adds to her ability to highlight market dynamics.Named a Power Woman of San Diego 2020 and PRSA's PR Professional of the Year in 2011, Rachel has built a reputation for her positive energy, creativity and humor. She received her MA in communications and media studies at San Diego State University and her BA in English/ History from University of Maryland, Baltimore County. Rachel has presented on communications strategy to PR News, PR Week, The International PR Research Conference, NC State and San Diego State University. You can find Rachel HERE More on Ford Hutman Media HERE Subscribe HERE for exclusive access and bonus episodes!This is an episode that you do not want to miss!Also, if you haven't already done so already, follow the podcast on LinkedIn HERE.  I'm adding a bunch of bonus episodes to the feed and, if you're not following, there's a good chance you'll miss out.Join 1K+ women receiving  my weekly newsletter where I help YOU level up your recruiting skills, share market insights also with all the tips on how to recruit your next Rockstar HERE Thanks for listening! Support the show

RNAi is complicated! Join us as we talk with Dr. Steve Whitham from Iowa State about the infection process of plant viruses, the RNAi process, and some ways we use this technology.

Bruce Potter, Extension Integrated Pet Management Specialist at the University of Minnesota, shares his perspective of the current state of corn rootworm management.

A new editorial paper was published in Oncotarget's Volume 14 on May 4, 2023, entitled, “AGO2 in T-prolymphocytic leukemia: its canonical and noncanonical deregulation and function.” In their new editorial, researchers Till Braun, Hanna Klepzig and Marco Herling from University of Cologne and University of Leipzig T-prolymphocytic leukemia (T-PLL) — a mature T-cell neoplasm with an aggressive and treatment refractory course. “In light of limited therapeutic options median overall survival times from diagnosis is hardly longer than 2 years.” There is currently no FDA- or EMA-approved drug for the treatment of T-PLL. Although 80–90% of patients experience a response to the most efficient single agent Alemtuzumab, relapses are common within the first 12–24 months following this first-line treatment. One of the defining characteristics of T-PLL is the presence of the chromosomal aberrations inv(14) or t(14;14), which lead to constitutive expression of the proto-oncogene T-cell leukemia 1A (TCL1A). This adapter molecule is centrally implicated in the enhanced T-cell receptor (TCR) signaling that is observed in the memorytype malignant T-cell. Other recurrent genomic alterations that have been identified in T-PLL affect the genes ataxia telangiectasia mutated (ATM), Janus kinase (JAK), signal transducer and activator of transcription (STAT), and MYC. In a recent study published by Braun et al., the team made significant advances in the understanding of the biology of T-PLL at the level of post-transcriptional gene regulation. “For the first time, descriptive and mechanistic data implicated the involvement of molecules of the RNA interference (RNAi) machinery in T-PLL's leukemogenesis and by that refined our current disease model by concepts beyond protein-coding genes.” DOI - https://doi.org/10.18632/oncotarget.28378 Correspondence to - Marco Herling - marco.herling@medizin.uni-leipzig.de Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28378 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, leukemia, T-PLL, AGO2, microRNA About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

In this episode, we dive into the world of corn rootworm pressure and the revolutionary SmartStax® PRO with RNAi Technology. Our Lead Agronomist, Craig, sheds light on the various methods used to evaluate rootworm pressure and the unique challenges faced in 2023 due to heavy insect pressure. Discover the intricacies of the SmartStax® PRO trait and how it addresses rootworm larvae control differently from traditional traits. Understand the implications of early root feeding and the long-term benefits of reduced rootworm adults through the RNAi Technology. Join us for a great discussion on the importance of field evaluations and monitoring adult rootworm beetle activity to make informed decisions for successful crop management. --- Send in a voice message: https://podcasters.spotify.com/pod/show/corneliusseed/message

RNA Interference, known as RNAi, is a biological process that leads to the silencing of gene expression.  A lot of plant viruses are RNA viruses including grapevine leafroll-associated virus and grapevine red blotch virus. Yen-Wen Kuo, Assistant Project Scientist in the Department of Plant Pathology at the University of California, Davis is researching ways to induce RNAi in grapevines to target virus. Growers may have heard of double-stranded RNA sprays which are intended to initiate RNAi. The challenge has been that double-stranded RNA breaks down quickly in the elements. The Kou lab is working to improve this process and look for alternatives that will have little impact on the ecology. Resources: 71: New Techniques to Detect Grapevine Leafroll Disease 131: Virus Detection in Grapevines Abstract: Development of Agrobacterium tumefaciens Infiltration of Infectious Clones of Grapevine Geminivirus A Directly into Greenhouse-Grown Grapevine and Nicotiana benthamiana Plants Kuo Laboratory – Plant Virology Maher Al Rwahnih, Foundation plant services RNA-Based Vaccination of Plants for Control of Viruses Yen-wen Kuo's Google Scholar page Vineyard Team Programs: Juan Nevarez Memorial Scholarship - Donate SIP Certified – Show your care for the people and planet   Sustainable Ag Expo – The premiere winegrowing event of the year Sustainable Winegrowing Education On-Demand (Western SARE) – Sign Up! Vineyard Team – Become a Member Get More Subscribe wherever you listen so you never miss an episode on the latest science and research with the Sustainable Winegrowing Podcast. Since 1994, Vineyard Team has been your resource for workshops and field demonstrations, research, and events dedicated to the stewardship of our natural resources. Learn more at www.vineyardteam.org.   Transcript Craig Macmillan  0:00  Our guest today is Yen-Wen Kuo. And she is Assistant Professor in the Department of Plant Pathology at UC Davis. I'm Craig Macmillan, your host, and I'm very excited to have Dr. Koh here with us today. Welcome.   Yen-Wen Kuo  0:11  Thank you for having me.   Craig Macmillan  0:13  So you've been doing some interesting work the lab on interference RNA, and also how it affects plant viruses and possibly insects in the future. Can you explain for those of us that did not take genetics like we were supposed to in college, what interference RNA is and how it works?   Yen-Wen Kuo  0:29  Sure. So RNA interference is a biological process in which certain types of RNA RNAs can trigger RNA interference. And then once it's triggered, it will produce specifics more RNAs, that can regulate gene expression, by degrading or binding to the target RNAs containing a homologous sequence containing a similar sequence of those small RNAs. So this is a general concept of RNA interference, we also call it RNAi is very complicated the whole process. And there are different pathways and mechanisms included in the RNA interference. RNAi is a primary and effective antiviral defense in plants, but also found in some fungi and insects and lower eukaryotes. And because of all these different mechanisms, scientists and researchers, they they work on different aspects of this mechanism for either plants or animals. And they're also looking for different potential and better ways to use RNAi for different applications.   Craig Macmillan  1:45  So if I understand correctly, you have cell and there is DNA in that cell, and there's genes that code for certain things. And so the RNA is was transmitting or was carrying information from that's encoded with the gene out into the world to do something, is that a fair explanation?   Yen-Wen Kuo  2:05  So the genome there in plants or animals and human is their DNA genomes is DNA, and then the DNA will transcribed into RNA. And those RNA, some of the messenger RNAs can translate into proteins. So it's a how the central dogma from DNA makes RNA and then RNA makes protein. In the old days, we thought that oh, the protein is the important things because the protein can have different functional, different functions in different ways to to regulate everything in the body or in different organisms. But then afterwards, we found that actually RNAs they have many different forms and they can function at the RNA level. So it can interfere with gene expressions and many different things.   Craig Macmillan  3:03  And how does this apply to plant viruses because you've done some really exciting work with Gemini viruses, I believe with grapevine virus a Tell me a little bit about that work and how that works.   Yen-Wen Kuo  3:15  A lot of plant viruses, they are RNA viruses, a lot of those devastating viruses in grapevines, for example, grapevine leaf roll associated virus or grapevine red blotch virus they. So grapevine leaf roll associated viruses and RNA virus and grapevine red blotch is DNA virus. So there are different types of viruses. And so my work is trying to use different viruses making them into viral vectors to induce RNAi in Grapevine plants, to target those important viruses causing diseases in the field for the grapevines. And because so for example, when the viruses they are infecting plants, they will trigger RNAi in the plant, so that plants can protect themselves from virus infection. And because of that, we're trying to develop viral vectors can trigger RNA interference to target those viruses that's causing diseases. The work I have on the grapevine Gemini virus A that GGVA is to either develop the virus into viral vectors to target RNA virus first. So that's the initial plan for us to use. GGVA the grapevine Gemini virus A target grapevine leaf roll associated viruses. So before we eventually target that virus, we have to do a lot of different tests. We need to know if the clones the constructs or DNA constructs we have of this, GGVA can actually affect Gravelines plants, so we have to do that. And then we want to see if we can develop it into viral vector to carry the sequence we want them to express in grapevines to do the work we want them to do. So then we use it to target genes in the plants to see if they can silence the genes in the plants. So then we did that, we found that yes, we can use that viral vector to silence genes in plants. And then now we try to see that if we can use this viral vector to target other RNA viruses, or other grapevine RNA viruses, because we are actually at the same time developing different viral vectors, and one of them is GBA, is grapevine virus, a another's name, it can be very confusing. GGVA is a DNA virus. GVA is an RNA virus totally different to viruses. So since we have both viruses in the lab, so first, we try to prove the concept. We use the GGVA, the DNA virus, to target the GBA wild type virus, to see if we can see any effects. The GBA infection viral titers in the infected grapevines. So this is what we're working on right now. And so eventually, we want to use this viral vector, and potentially other viral vectors to to target grapevine leaf roll associated virus. And maybe we can use it to target mealybugs too.   Craig Macmillan  6:35  How are these vectors introduced to the plant?   Yen-Wen Kuo  6:38  We modify from the previous reports how people try to deliver those constructs the plasmids into grapevines. Most of the experiments or the assays, from before, they needed to have grapevine plants grown from in vitro, on media or from embryos. But that's really a lot of work. And it will be harder to have applications in the field. So then we develop vacuuming filtration method that we can directly vacuum infiltrate those plasmids that those DNA construct plasmids directly into the greenhouse grown grapevine plants. So those plants are propagated from the cuttings and then those plants, they are usually maybe 12 to 19 inches high above the soil when we infiltrated those plasmids into those grow vine plants. So this is an we got pretty good results, we successfully introduced those DNA constructs into the grapevine plans and those constructs can be infectious and initiate the whole the virus replicate in the grapevine.   Craig Macmillan  7:50  So is this something that can be done in a nursery then with new plants? And basically, they then would come with the vector or is it something you could do in the field?   Yen-Wen Kuo  7:57  Yes, I think the plan is that we can introduce those plasmas in the nursery in greenhouse plants before we plant them into the field. So then the plants that's planted into the field, they can have this viral vector to protect the plants from specific viruses.   Craig Macmillan  8:18  Got it. That's really neat. That's a great idea. And it's pretty cool. So that's fantastic. And in the work that you're doing so far, it sounds really exciting. And it sounds like the direction that you're kind of going in the future is with leaf roll virus that you mentioned. And then also, interaction with mealybugs you mentioned. Can you tell me more about that? What's that work all about?   Yen-Wen Kuo  8:39  Because this virus does GGVA and other viral vectors we're working on to a lot of viruses infecting grape vines, their phloem limited virus, so this GGVA is also phloem limited, meaning that the virus is can only infect the tissues around or in the phloem  is restricted. It doesn't go to like mesophyll cells or epidermal cells in infected plants, because mealybugs they feed on phloems. So we think if they can pick up those RNA interference signals, may be those RNA interference signals those small RNAs can target mealybugs too. So we can choose different target sequences in mealybugs. Hopefully you can see some effects for many bucks to to prevent that from transmitting viruses or have lethal effects for mealybugs. That's the plan. Hopefully we can do that. But we have to do tests to see how the efficacy and everything though it can have mealybugs, because there are previously they are different studies they use RNAi on insects, and many people prove that they can see some effects. We hope that the viral vector approach can also use for really apply this into the field for grapevine plants.   Craig Macmillan  10:00  What kind of index on insects are we talking about?   Yen-Wen Kuo  10:03  Depends on what target genes or sequences we choose. For my first choice, I would like to have a target that can prevent the transmission of the virus by mealybug, that will be my choice. I'm not sure if it's good to kill the insects, if it's going to affect the ecology too much. So if we can make the mealybug not transmitting the virus or other diseases, I think there will be a very good first step if we can see a lower transmission rate. And and then we can see if we need to adjust from there.   Craig Macmillan  10:40  That is amazing. And we haven't, yeah, the little bit of research that I did we have we do have proof of concept basically on this in other cropping systems. Is that right?   Yen-Wen Kuo  10:55  Yes,   Craig Macmillan  10:55  Can you tell me a little bit more about that, because that might give us some some vision of where we might go in the vineyard industry.   Yen-Wen Kuo  11:01  So, the RNAi applications, people are already trying to do some of those works. So, one example is that before people can spray double stranded RNA into the field. So, let me talk a little bit about the introduction of why using double stranded RNA. So, there are different types of RNAs that can induce RNA interference, certain types, one of them is double stranded RNA, either double stranded RNA or the single stranded RNA, they can form into a secondary structure in folding into a structure like a hairpin RNA, those are found to be able to induce RNA interference. And there's also other things like artificial micro RNAs, there are different types of RNAs that can induce RNAi and most convenient ways to make double stranded RNA. And people have been synthesizing the double stranded RNA or using bacteria to produce those double stranded RNA and then spraying to the field to get some protection for the plants. It worked at some level, but it's just not stable enough. Although double stranded RNA is more stable compared to single stranded RNA, steroids and RNA can be degraded in the field with the sun and everything the whole environment it can be degraded, people started to look for ways like bio clay to protect the RNA, and then so, they can spray in the field. So, the RNA can last longer and cause the effects. So, those double stranded RNAs can be absorbed by the insects, they can pick up from the surface of the plant or the plant can absorb those double stranded RNA into the plants. So, those are different ways and people started to see some effects on that, but still, we have to improve those different methods delivering double stranded RNA or other types of RNA to induce RNA interference in the plant. So, they are different different approaches. So, one of that is now we are trying using virus to introduce the RNAi to induce the RNAi in the plants. So, people are trying different ways to deliver those specific RNAs to induce RNAi to target specific diseases, sometimes not just viral diseases, that they will try to target fungal disease or something else and insects. This is what many different groups they are trying to do also previously, another way is to try to make transgenic plants. So if we can make plants to express those RNAs that can induce RNAi targeting to specific diseases, then you don't need to really use any tool to the deliver because the transgenic plants itself can produce those RNAs doing to induce RNAi plants. So that's also another way that people are trying to do we call that host induced gene silencing HIGS, and the virus induced gene silencing is the way my group is working on and we call it VIGs vigs. So there are different ways that which we would use to introduce those RNAs to induce RNAi in the plants.   Craig Macmillan  14:31  And right now you are at the greenhouse stage, if I understand correctly.   Yen-Wen Kuo  14:35  Yes.   Craig Macmillan  14:36  Have you introduced mealybug into your experiments into your work yet?   Yen-Wen Kuo  14:40  Not yet. We are just working on targeting grapevine virus first to see the effects. So where we have to continue monitoring those tested plants to see if the effects can last long, and the efficacy and how good they can be. So now we're at four for five months, so it's still we can see the targeted virus is being suppressed in a very, very low titer. So GVA can cause some symptoms in the grapevine plants when they see the plans are infected. But we have to peel off the bark to see the symptoms, we want to see that after targeting to the GBA virus, we saw that the viral titer is very low, if we can see that, also, the symptoms is not there anymore, is now like wild type, when when the virus was infecting in the plants alone, if we can see the difference, we don't even see the symptoms there will be really great. And this part, hopefully I can collaborate with the collaborators, Maher, he's run the foundation plan services, he can help my group on this, to see that how good the effects can be using this GGVA viral vector. So after that, if we can successfully target two different viruses, then we will start to work to change the target sequence in this viral vector to target mealybugs. So that's after the virus work.   Craig Macmillan  16:12  Yeah, well, that's very exciting. This is a really fascinating idea, and obviously is still relatively new. And I think it's really great that you and everybody else is working on this sounds like there's tremendous potential, and I hope that you folks continue on are able to continue on, is there one thing really related to this topic, you would tell growers one thing that you would advise them or you would educate them with?   Yen-Wen Kuo  16:34  I understand that there could be some concerns and maybe doubts, questioning RNAi applications in the field, because before, they already probably heard about the spray of double stranded RNA or other methods, and they saw some effects but not stable enough. So they may have some concerns or doubts, I think many scientists are trying different delivery methods that can be applied efficiently in the field. And we will do different types of tests and trials to make sure we work on any potential issues of this technology before applying them in the field and try not to affect the whole ecology or anything in the field too. And obviously, the current approaches we have are not enough to keep certain grapevine diseases, at low enough incidence. So we have to explore more potential control approaches before those diseases get worse, and adjust the ways to manage those different grapevine diseases with this changing environment. And I think hopefully, we can all work together to achieve this same goal. And I understand this is something new, I hope everyone can keep an open mind and willing to work with us to do different trials and see if we can improve different approaches to control different diseases.   Craig Macmillan  17:58  Well, I hope so too. grape growers are very creative. And they're always looking for solutions to their problems that very much fit what you're describing. And it sounds to me, this could be another tool in the IPM toolbox that may not be the single solution may not be a silver bullet. But it sounds very exciting that it may play a very important role to improve the efficacy of other techniques we have, which is great. Where can people find out more about you?   Yen-Wen Kuo  18:22  So because I will, setting up my lab, so hopefully I can have a lab website soon. I don't have accounts at Twitter or Instagram.   Craig Macmillan  18:34  Neither do I.   Yen-Wen Kuo  18:36  I don't use social media a lot. So my email that people can reach me through the email. And hopefully, when this is up or in your podcast, I will have my lab website set up so people can find us our work, my lab website.   Craig Macmillan  18:53  And we will have links and everything else that we can find posted on the episode page at the Vineyard Team podcast website. I want to thank you for being on the program. This was really, really interesting and is a kind of a view into the future of what's possible. Yeah. Our guest today was Dr. Yen-Wen Kuo. She is with the Department of Plant Pathology at the University of California Davis. And I want to thank you for being on the podcast.   Yen-Wen Kuo  19:20  Thank you for having me on the show. I really appreciate this opportunity to talk about research to explain some details about our work to the course and hopefully, I answer some questions that growers might have. I look forward to in the future maybe collaborating with different people to make this thing to work.   Nearly Perfect Transcription by https://otter.ai

Professor Eriks Rozners and colleagues at Binghamton University in New York, USA, are using innovative nucleic acid chemistry to modify RNA-based technologies such as RNA interference and CRISPR to enhance their utility in molecular biology. These technologies suffer from off-target effects that limit their clinical utility. By replacing phosphates in the backbone with amides, the team aims to improve the stability, specificity, and uptake of these technologies by cells to make them more suitable for in vivo applications.Read the original article: doi.org/10.1021/acschembio.2c00769Read more in Research Outreach

Advancements in RNA interference (RNAi) technology could soon unlock new tools for managing canola pests and pathogens, such as sclerotinia and flea beetles. RNAi — ribonucleic acid interference — involves targeting specific RNA sequences in a disease or pest, rather than targeting entire proteins or enzymes, as is the case with current pesticides. It’s a... Read More

The convergence of Artificial Intelligence (AI) and biotechnology has emerged as one of the most exciting and transformative areas of science. Researchers are developing new tools and technology that could bring about breakthroughs to revolutionize the fields of medicine and health care.  In this episode, we talk with scientists who are using AI to unlock new possibilities in the search for novel drugs, cures, and treatments.

This episode is proudly sponsored by our partner, Alnylam Pharmaceuticals, the leading RNAi therapeutics company. When Stan Crooke ran Ionis and John Maraganore ran Alnylam, they were partners that turned into rivals — and not always friendly ones — as they persevered to pursue an entirely new therapeutic space; RNA-targeted drug discovery and development. Now, the pair of drug discovery titans have united once again in support of Dr. Crooke's n-Lorem Foundation—working to provide personalized medicines to the rarest of rare disease patients (nano-rare) using the antisense oligonucleotide (ASO) technology Stan led the creation of at Ionis. In this episode, Stan has a conversation with Dr. John Maraganore about John's past, their former rivalry, and the optimism shared between the two with respect to a better future for nano-rare patients.On This Episode We Discuss:- Being a dream merchant and driving a dream into a real therapeutic platform- Founding of Regulus and the synergy between Ionis and Alnylam throughout the years- What happens when two very competitive CEO-scientists have competing drugs- Overcoming their differences- Giving hope to a patient and their family with nano-rare diseases is powerful- Saving the world one life at a time- Bringing ASO and RNAi technologies together to collaboratively help nano-rare patients- A sustainable non-profit model?- Hope – a powerful thing to lose and an important thing to recover

The convergence of Artificial Intelligence (AI) and biotechnology has emerged as one of the most exciting and transformative areas of science. Researchers are developing new tools and technology that could bring about breakthroughs to revolutionize the fields of medicine and health care.  In this episode, we talk with scientists who are using AI to unlock new possibilities in the search for novel drugs, cures, and treatments.

Dr. Edwin Benkert III gives an in-depth look at insecticides, rotational practices, and RNAi, the newest technology in 2023! Join us as we get in-depth ideas on best management practices for corn on corn fields in 2023.