Podcasts about rna interference

In this episode of IDEA Collider, we dive into the world of biotech innovation with John Maraganore, former CEO of Alnylam Pharmaceuticals. Recognized as a trailblazer, John transformed RNA interference from a scientific concept into a revolutionary class of medicines, leading the development of five life-changing drugs. Join us as we explore John's journey from a first-generation American with Greek immigrant parents to a key figure in biomedicine. We'll discuss his education at the University of Chicago, his leadership role at Alnylam, drug delivery challenges for RNAi therapeutics, and the importance of strategic pharmaceutical alliances. John also shares his take on the current biotech environment, the impact of policy and regulation, and the promising future of genetic medicines and AI in drug discovery. Chapter Summaries;00:00 Introduction to John Maraganore: Biotech Trailblazer01:11 John's Early Life and Education03:09 Joining Alnylam and the RNAi Revolution04:56 Challenges and Successes at Alnylam06:47 Current Biotech Funding Environment08:17 Global Competition and US Leadership in Biotech10:25 The Importance of In-Person Collaboration12:01 Overcoming Drug Delivery Hurdles15:21 Maintaining an Entrepreneurial Spirit in Biotech17:00 Balancing Science and Business in Decision Making20:27 Strategic Partnerships in Biotech23:36 The Role of Biotech in Global Challenges26:25 Advocating for Policy Changes in Biotech30:41 Mentoring the Next Generation of Biotech Leaders32:35 Future Frontiers in Biotech Innovation36:08 John's Vision for the Future of Biomedicine37:18 Communicating Innovation and LeadershipDon't forget to Like, Share, Subscribe, Rate, and Review! Keep up with John Maraganore;LinkedIn: https://www.linkedin.com/in/john-maraganore/ Follow Mike Rea On;Website: https://www.ideapharma.com/X: https://x.com/ideapharmaLinkedIn: https://www.linkedin.com/in/bigidea/ Listen to more fantastic podcast episodes: https://podcast.ideapharma.com/

Mazen Noureddin and Naim Alkhouri join Jörn Schattenberg and Roger Green to discuss some of the other major drug development stories from the EASL Congress 2024, with special focus on denifenstat, ION-224 and TAK-227, and to review the SPECIAL study on bariatric surgery and cirrhosis. The panelists concur that all three of these agents have potential value in therapy. Naim expresses some concern about how broad denifestat use will be based on its side effect profile. Later in this conversation, Mazen belives that denifenstat has broad potential for use, given that the most prominent side effect, hair thinning, appears transient and readily manageable. He also notes that denifenstat's impressive results were based on Intent to Treat analysis, which is more rigorous.  Naim states his interest in the ION-224 agent based on its mode of action, which is RNA interference. He also discusses SPECIAL, a study he conducted with the bariatric surgery group at Cleveland Clinic. This study, which evaluated patients with cirrhosis at the time of surgery, demonstrated a 72% risk reduction in major adverse liver outcomes over a 10-year period and 80% risk reduction in decompensation. Jörn discusses a study he presented on TAK-227, a TG2 inhibitor originally developed for celiac disease. Early results here are quite promising and, as Aleksander Krag mentioned in S5 E17, demonstrates exciting potential for collaboration with drug developers for other diseases. As the conversation ends, Roger asks Mazen and Jörn what they consider likely to be the biggest MASLD stories at the AASLD Liver Congress in November. Mazen selects the Phase 3 ESSENCE study for semaglutide, while Jörn suggests NITs. 

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.  

Dr. Steve Whitham joins us to discuss the challenges of plant viruses.  This complex conversation helps us understand key considerations when thinking about corn virus management.   We also discuss RNA interference in agriculture and food production systems.

Impact: Zilebesiran

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

Emerging therapeutics based on gene addition, editing, or silencing are expected to change the landscape of genetic liver disease.Watch this episode to find out:Which approaches exist?Where are they in terms of preclinical and clinical development?How will they be used?FacultyDr Mattias Mandorfer (Moderator)Dr Gloria Gonzalez-Aseguinolaza (Faculty)Prof. Pavel Strnad (Faculty)Prof. Man-Fung Yuen (Faculty)All EASL Studio Podcasts are available on EASL Campus.

Huberman Lab Podcast Notes Key Takeaways Genes and patterns of inheritance shape our lives and who we areMost people get the concept of epigenetic inheritance wrong – it really means that the environment of the parent somehow changed future childrenBottom line, we need larger studies to understand the extent of epigenetics – it's also difficult to design because we have to control environmental effectsFor memories to pass through generations, there has to be a transformation of the neural circuit into the nucleotide sequences contained in DNA or RNA (more likely) The transformation of one set of physical points to a translation of points in genetic points needs to take placeTrue epigenetic effect has been observed in c. elegans: it was shown that the brain can communicate with the next generation using small RNAs and this can change behavior in 3 generations without using any languageRead the full notes @ podcastnotes.orgIn this episode, my guest is Oded Rechavi, Ph.D., professor of neurobiology at Tel Aviv University and expert in how genes are inherited, how experiences shape genes and remarkably, how some memories of experiences can be passed via genes to offspring. We discuss his research challenging long-held tenets of genetic inheritance and the relevance of those findings to understanding key biological and psychological processes including metabolism, stress and trauma. He describes the history of the scientific exploration of the “heritability of acquired traits” and how epigenetics and RNA biology can account for some of the passage of certain experience-based memories. He discusses the importance of model organisms in scientific research and describes his work on how stressors and memories can be passed through small RNA molecules to multiple generations of offspring in ways that meaningfully affect their behavior. Nature vs. nurture is a commonly debated theme; Dr. Rechavi's work represents a fundamental shift in our understanding of that debate, as well as genetic inheritance, brain function and evolution. For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman ROKA: https://roka.com/huberman HVMN: https://hvmn.com/huberman Eight Sleep: https://eightsleep.com/huberman InsideTracker: https://www.insidetracker.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Timestamps (00:00:00) Dr. Oded Rechavi (00:02:08) Sponsors: ROKA, HVMN, Eight Sleep (00:06:04) DNA, RNA, Protein; Somatic vs. Germ Cells (00:14:36) Lamarckian Evolution, Inheritance of Acquired Traits (00:22:54) Paul Kammerer & Toad Morphology (00:28:52) AG1 (Athletic Greens) (00:30:06) James McConnell & Memory Transfer (00:37:31) Weismann Barrier; Epigenetics  (00:45:13) Epigenetic Reprogramming; Imprinted Genes  (00:50:43) Nature vs. Nurture; Epigenetics & Offspring (00:59:06) Generational Epigenetic Inheritance  (01:09:03) Sponsor: InsideTracker (01:10:20) Model Organisms, C. elegans (01:21:50) C. elegans & Inheritance of Acquired Traits, Small RNAs (01:26:02) RNA Interference, C. elegans & Virus Immunity (01:34:13) RNA Amplification, Multi-Generational Effects (01:38:41) Response Duration & Environment (01:47:50) Generational Memory Transmission, RNA (01:59:36) Germ Cells & Behavior; Body Cues (02:04:48) Transmission of Sexual Choice (02:11:22) Fertility & Human Disease; 3-Parent In Vitro Fertilization (IVF); RNA Testing (02:17:56) Deliberate Cold Exposure, Learning & Memory (02:29:26) Zero-Cost Support, Spotify & Apple Reviews, YouTube Feedback, Sponsors, Momentous, Social Media, Neural Network Newsletter Title Card Photo Credit: Mike Blabac Disclaimer

In this episode, my guest is Oded Rechavi, Ph.D., professor of neurobiology at Tel Aviv University and expert in how genes are inherited, how experiences shape genes and remarkably, how some memories of experiences can be passed via genes to offspring. We discuss his research challenging long-held tenets of genetic inheritance and the relevance of those findings to understanding key biological and psychological processes including metabolism, stress and trauma. He describes the history of the scientific exploration of the “heritability of acquired traits” and how epigenetics and RNA biology can account for some of the passage of certain experience-based memories. He discusses the importance of model organisms in scientific research and describes his work on how stressors and memories can be passed through small RNA molecules to multiple generations of offspring in ways that meaningfully affect their behavior. Nature vs. nurture is a commonly debated theme; Dr. Rechavi's work represents a fundamental shift in our understanding of that debate, as well as genetic inheritance, brain function and evolution. For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman ROKA: https://roka.com/huberman HVMN: https://hvmn.com/huberman Eight Sleep: https://eightsleep.com/huberman InsideTracker: https://www.insidetracker.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Timestamps (00:00:00) Dr. Oded Rechavi (00:02:08) Sponsors: ROKA, HVMN, Eight Sleep (00:06:04) DNA, RNA, Protein; Somatic vs. Germ Cells (00:14:36) Lamarckian Evolution, Inheritance of Acquired Traits (00:22:54) Paul Kammerer & Toad Morphology (00:28:52) AG1 (Athletic Greens) (00:30:06) James McConnell & Memory Transfer (00:37:31) Weismann Barrier; Epigenetics  (00:45:13) Epigenetic Reprogramming; Imprinted Genes  (00:50:43) Nature vs. Nurture; Epigenetics & Offspring (00:59:06) Generational Epigenetic Inheritance  (01:09:03) Sponsor: InsideTracker (01:10:20) Model Organisms, C. elegans (01:21:50) C. elegans & Inheritance of Acquired Traits, Small RNAs (01:26:02) RNA Interference, C. elegans & Virus Immunity (01:34:13) RNA Amplification, Multi-Generational Effects (01:38:41) Response Duration & Environment (01:47:50) Generational Memory Transmission, RNA (01:59:36) Germ Cells & Behavior; Body Cues (02:04:48) Transmission of Sexual Choice (02:11:22) Fertility & Human Disease; 3-Parent In Vitro Fertilization (IVF); RNA Testing (02:17:56) Deliberate Cold Exposure, Learning & Memory (02:29:26) Zero-Cost Support, Spotify & Apple Reviews, YouTube Feedback, Sponsors, Momentous, Social Media, Neural Network Newsletter Title Card Photo Credit: Mike Blabac Disclaimer

In this episode Jeffrey continues his appearance on the Real Truth About Health conference and discusses RNA interference which allows the reprogramming of gene expression.  RNA Interference is already being used in the production of the Arctic Apple which will not turn brown if you slice it.  The genetic engineers add a piece of RNA to the apple that finds its DNA counterpart and silences that DNA expression.  We know from research on mammals, insects, others that that double stranded RNA that silences that stretch of DNA can also theoretically, silence ours. So if you bite that apple and that double stranded RNA starts circulating in our system, it might find a match. The Institute for Responsible Technology is working to protect you & the World from GMOs (and while we're at it, Roundup®...)  To find out exactly how we do this and to subscribe to our newsletter visit https://www.responsibletechnology.org/ Join us at Protect Nature Now to Safeguarding Biological Evolution from GMOs 2.0. The place to get critical up to date information, watch our short film and most importantly, learn easy ways for you to take action against this existential threat. Visit: https://protectnaturenow.com/ Watch "Don't Let the Gene Out of the Bottle" Get the book: "Seeds of Deception" IG @irtnogmos Facebook @responsibletechnology YouTube @TheInstituteforResponsibleTechinology Twitter @TheInstituteforResponsibleTechnology

In this episode, the editorial team discusses the FDA approval of Cyltezo as the first interchangeable biosimilar for AbbVie's Humira. The approval lends to the growing Humira biosimilars market, which will take off in 2023 with Boehringer Ingelheim's Cyltezo and biosimilars from Amgen, Merck and Alvotech. AbbVie has been facing a lot of heat over accusations of price gouging and patent abuses to block Humira biosimilars from entering the market. The team had an interesting discussion about public perceptions of generics and biosimilars versus their originals/reference products.Ayesha also talked about a new gene silencing treatment for porphyria called Givlaari that received recommendation from England's NICE after having been initially rejected by the health watchdog last year. Additionally, long-term results from a late-stage trial for Givlaari were recently released, which showed that the treatment provides sustained benefit and has a good safety profile. However, the team discussed the high cost of the treatment, which is a concern for patients in countries that don't have some form of socialized healthcare.Read the full articles here: Cyltezo Becomes First FDA-Approved Interchangeable Humira Biosimilar Gene Silencing Porphyria Treatment, Givlaari, Finally Wins Over England's NICE Amid Stellar Long-Term Data For more life science and medical device content, visit the Xtalks Vitals homepage.Follow Us on Social MediaTwitter: @Xtalks Instagram: @Xtalks Facebook: https://www.facebook.com/Xtalks.Webinars/ LinkedIn: https://www.linkedin.com/company/xtalks-webconferences YouTube: https://www.youtube.com/c/XtalksWebinars/featured

Go online to PeerView.com/WUP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in hemophilia explores the evidence supporting novel, emerging hemophilia therapeutics and provides guidance on the implications of the evidence presented for real-world practice. Upon completion of this accredited CE activity, participants should be better able to: Discuss current challenges and new developments in the management of patients with hemophilia A and B, Review the mechanism of action of RNA interference and the role of novel, investigational nonfactor replacement therapies in hemophilia A and B, Evaluate the safety and efficacy profiles and clinical trial data for emerging nonfactor, nongene therapies for treating patients with hemophilia A and B with or without inhibitors.

Go online to PeerView.com/WUP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in hemophilia explores the evidence supporting novel, emerging hemophilia therapeutics and provides guidance on the implications of the evidence presented for real-world practice. Upon completion of this accredited CE activity, participants should be better able to: Discuss current challenges and new developments in the management of patients with hemophilia A and B, Review the mechanism of action of RNA interference and the role of novel, investigational nonfactor replacement therapies in hemophilia A and B, Evaluate the safety and efficacy profiles and clinical trial data for emerging nonfactor, nongene therapies for treating patients with hemophilia A and B with or without inhibitors.

Go online to PeerView.com/WUP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in hemophilia explores the evidence supporting novel, emerging hemophilia therapeutics and provides guidance on the implications of the evidence presented for real-world practice. Upon completion of this accredited CE activity, participants should be better able to: Discuss current challenges and new developments in the management of patients with hemophilia A and B, Review the mechanism of action of RNA interference and the role of novel, investigational nonfactor replacement therapies in hemophilia A and B, Evaluate the safety and efficacy profiles and clinical trial data for emerging nonfactor, nongene therapies for treating patients with hemophilia A and B with or without inhibitors.

Go online to PeerView.com/WUP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in hemophilia explores the evidence supporting novel, emerging hemophilia therapeutics and provides guidance on the implications of the evidence presented for real-world practice. Upon completion of this accredited CE activity, participants should be better able to: Discuss current challenges and new developments in the management of patients with hemophilia A and B, Review the mechanism of action of RNA interference and the role of novel, investigational nonfactor replacement therapies in hemophilia A and B, Evaluate the safety and efficacy profiles and clinical trial data for emerging nonfactor, nongene therapies for treating patients with hemophilia A and B with or without inhibitors.

Go online to PeerView.com/WUP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in hemophilia explores the evidence supporting novel, emerging hemophilia therapeutics and provides guidance on the implications of the evidence presented for real-world practice. Upon completion of this accredited CE activity, participants should be better able to: Discuss current challenges and new developments in the management of patients with hemophilia A and B, Review the mechanism of action of RNA interference and the role of novel, investigational nonfactor replacement therapies in hemophilia A and B, Evaluate the safety and efficacy profiles and clinical trial data for emerging nonfactor, nongene therapies for treating patients with hemophilia A and B with or without inhibitors.

Go online to PeerView.com/WUP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in hemophilia explores the evidence supporting novel, emerging hemophilia therapeutics and provides guidance on the implications of the evidence presented for real-world practice. Upon completion of this accredited CE activity, participants should be better able to: Discuss current challenges and new developments in the management of patients with hemophilia A and B, Review the mechanism of action of RNA interference and the role of novel, investigational nonfactor replacement therapies in hemophilia A and B, Evaluate the safety and efficacy profiles and clinical trial data for emerging nonfactor, nongene therapies for treating patients with hemophilia A and B with or without inhibitors.

Go online to PeerView.com/WUP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in hemophilia explores the evidence supporting novel, emerging hemophilia therapeutics and provides guidance on the implications of the evidence presented for real-world practice. Upon completion of this accredited CE activity, participants should be better able to: Discuss current challenges and new developments in the management of patients with hemophilia A and B, Review the mechanism of action of RNA interference and the role of novel, investigational nonfactor replacement therapies in hemophilia A and B, Evaluate the safety and efficacy profiles and clinical trial data for emerging nonfactor, nongene therapies for treating patients with hemophilia A and B with or without inhibitors.

Go online to PeerView.com/WUP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in hemophilia explores the evidence supporting novel, emerging hemophilia therapeutics and provides guidance on the implications of the evidence presented for real-world practice. Upon completion of this accredited CE activity, participants should be better able to: Discuss current challenges and new developments in the management of patients with hemophilia A and B, Review the mechanism of action of RNA interference and the role of novel, investigational nonfactor replacement therapies in hemophilia A and B, Evaluate the safety and efficacy profiles and clinical trial data for emerging nonfactor, nongene therapies for treating patients with hemophilia A and B with or without inhibitors.

Go online to PeerView.com/WUP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in hemophilia explores the evidence supporting novel, emerging hemophilia therapeutics and provides guidance on the implications of the evidence presented for real-world practice. Upon completion of this accredited CE activity, participants should be better able to: Discuss current challenges and new developments in the management of patients with hemophilia A and B, Review the mechanism of action of RNA interference and the role of novel, investigational nonfactor replacement therapies in hemophilia A and B, Evaluate the safety and efficacy profiles and clinical trial data for emerging nonfactor, nongene therapies for treating patients with hemophilia A and B with or without inhibitors.

Go online to PeerView.com/WUP860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in hemophilia explores the evidence supporting novel, emerging hemophilia therapeutics and provides guidance on the implications of the evidence presented for real-world practice. Upon completion of this accredited CE activity, participants should be better able to: Discuss current challenges and new developments in the management of patients with hemophilia A and B, Review the mechanism of action of RNA interference and the role of novel, investigational nonfactor replacement therapies in hemophilia A and B, Evaluate the safety and efficacy profiles and clinical trial data for emerging nonfactor, nongene therapies for treating patients with hemophilia A and B with or without inhibitors.

Dr. Andrew Fire won the Nobel Prize in Physiology or Medicine in 2006 for the discovery of RNA interference (RNAi). Dr. Fire is the George D. Smith Professor in Molecular and Genetic Medicine, and Professor of Pathology and Genetics at the Stanford University School of Medicine. He received his AB degree in mathematics from the University of California at Berkeley. He received his PhD in Biology from the Massachusetts Institute of Technology. He did training at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England as a fellow. Prior to Stanford he was part of the scientific staff at the Carnegie Institution of Washington. Tune in to learn about the mechanism of RNAi, how RNAi was discovered, and the clinical applications of RNAi.

(Content heavy!) Transcription, Structural Differences of Nucleic Acids, mRNA Processing, and RNA Interference

Phillip D. Zamore Bio: Phillip D. Zamore, Ph.D. has been an Investigator of the Howard Hughes Medical Institute since 2008. In 2016, he became the Chair of the RNA Therapeutics Institute, which was established at the University of Massachusetts Medical School in 2009. Dr. Zamore also is Professor of Biochemistry and Molecular Pharmacology, the department he joined in 1999, and he became the Gretchen Stone Cook Professor of Biomedical Sciences in 2005. Dr. Zamore received his A.B. (1986) and Ph.D. (1992) degrees in Biochemistry and Molecular Biology from Harvard University. He then pursued postdoctoral studies on the role of the RNA binding proteins in Drosophila development at The Whitehead Institute for Biomedical Research, in Cambridge, Massachusetts. Dr. Zamore's laboratory studies small RNA silencing pathways in eukaryotes and prokaryotes, including RNA interference (RNAi), microRNA, and PIWI-interacting RNA pathways. Dr. Zamore and his collaborators seek to use these insights to design therapies for human diseases, including Huntington's disease. Under Dr. Zamore's mentorship, the Zamore Lab has produced dozens of researchers working at top institutions both in the United States and abroad. In 2015, Dr. Zamore was awarded the Chancellor's Medal for Excellence in Scholarship at the University of Massachusetts Medical School. To date, Dr. Zamore has more than 150 publications and has been among the most highly cited researchers for more than a decade. He serves on the editorial boards of numerous journals and is in demand as a presenter at conferences and institutions worldwide. Dr. Zamore holds more than 20 patents, with other applications pending; he was elected a Fellow of the National Academy of Inventors in 2014. In 2002, Dr. Zamore co-founded Alnylam Pharmaceuticals (Cambridge, MA), a publicly traded biotech company which now has more than 1000 employees and multiple drugs in clinical trials. Alnylam's first drug, ONPATTRO, a first-of-its-kind RNAi therapeutic, for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults, was approved by the FDA in 2018. In 2014, he co-founded Voyager Therapeutics in Cambridge, MA. Chair and Professor at University of Massachusetts Medical School, Phillip Zamore, joins the show to discuss a new method of gene silencing called RNA interference (RNAi). Tune in to learn the following: How the RNAi system is analogous to the basis of vaccination How specifically the method of RNAi prevents a protein from being made and what happens to the mRNA after it has been cut Why RNAi will never replace the knock-out method, and the benefit of combining both methods  Zamore states that the world's diseases can be divided into two broad categories: those with mutations in the genome that can be addressed by turning off the gene forever, and those with mutations in the genome that can be addressed by lowering the amount of a gene product, as opposed to turning off the gene completely. The gene knock-out method is used for the first kind of disease, and the effects of the knock-out are irreversible. This makes the method a good tool for studying model organisms in the lab, but rather risky as a therapeutic intervention for humans. This is where a new method called RNA interference comes into play and holds promise for the future of medicine and the treatment of diseases. RNA interference is a way of destroying messenger RNA (mRNA) in order to prevent the creation of a protein. Unlike other methods, RNA interference uses a natural cellular pathway, which makes it more effective than other mechanisms in turning off disease genes. And just like taking a drug, stopping this process means stopping any unwanted side effects, which means it's a lot safer and less risky than the knock-out method. There are currently two RNAi drugs on the market, both of which direct small RNA (sRNA) to the liver where the protein in question is made. By way of preventing the creation of that protein, the disease gene is turned down (almost off). Zamore explains why the liver is particularly amenable to these drugs, and the ongoing research and development taking place for drugs that target proteins made in other areas of the body. He also discusses the near-term goal of bringing to market an sRNA drug that blocks the production of a protein in the cholesterol biosynthesis pathway. This drug would function as a replacement for statins, and comes with fewer side effects and would only need to be taken by a patient twice per year. Zamore brings an impressive amount of insight and information to the show, discussing a number of topics in depth but with enough clarity to follow along with ease. Learn more by visting his Google Scholar page at https://scholar.google.com/citations?user=xYLmV7YAAAAJ&hl=en.

Learn about a medical mystery involving blindness and schizophrenia; a new bacteria scientists developed to help protect honeybees; and the surprising strength of helmets used in World War I. No person who was born blind has ever been diagnosed with schizophrenia by Andrea Michelson Love, S. (2020, February 11). People Born Blind Are Mysteriously Protected From Schizophrenia. Vice; vice. https://www.vice.com/en_uk/article/939qbz/people-born-blind-are-mysteriously-protected-from-schizophrenia Morgan, V. A., Clark, M., Crewe, J., Valuri, G., Mackey, D. A., Badcock, J. C., & Jablensky, A. (2018). Congenital blindness is protective for schizophrenia and other psychotic illness. A whole-population study. Schizophrenia Research, 202, 414–416. https://doi.org/10.1016/j.schres.2018.06.061  Silverstein, S. M., Wang, Y., & Keane, B. P. (2013). Cognitive and Neuroplasticity Mechanisms by Which Congenital or Early Blindness May Confer a Protective Effect Against Schizophrenia. Frontiers in Psychology, 3. https://doi.org/10.3389/fpsyg.2012.00624  Steve Silverstein’s chart tracking skills associated with blindness and schizophrenia: https://www.frontiersin.org/files/Articles/40106/fpsyg-03-00624-r2/image_m/fpsyg-03-00624-t001.jpg Prediction of adult-onset schizophrenia from childhood home movies of the patients | American Journal of Psychiatry. (2020). American Journal of Psychiatry. https://ajp.psychiatryonline.org/doi/abs/10.1176/ajp.147.8.1052?journalCode=ajp&  Pollak, T. A., & Corlett, P. R. (2019). Blindness, Psychosis, and the Visual Construction of the World. Schizophrenia Bulletin. https://doi.org/10.1093/schbul/sbz098  Scientists have engineered bacteria to protect honeybees from colony collapse by Grant Currin Bacteria Engineered to Protect Bees from Pests and Pathogens - UT News. (2020, January 30). UT News. https://news.utexas.edu/2020/01/30/bacteria-engineered-to-protect-bees-from-pests-and-pathogens/  Leonard, S. P., Powell, J. E., Perutka, J., Geng, P., Heckmann, L. C., Horak, R. D., Davies, B. W., Ellington, A. D., Barrick, J. E., & Moran, N. A. (2020). Engineered symbionts activate honey bee immunity and limit pathogens. Science, 367(6477), 573–576. https://doi.org/10.1126/science.aax9039  Ramsey, S. D., Ochoa, R., Bauchan, G., Gulbronson, C., Mowery, J. D., Cohen, A., Lim, D., Joklik, J., Cicero, J. M., Ellis, J. D., Hawthorne, D., & vanEngelsdorp, D. (2019). Varroa destructor feeds primarily on honey bee fat body tissue and not hemolymph. Proceedings of the National Academy of Sciences, 116(5), 1792–1801. https://doi.org/10.1073/pnas.1818371116  US EPA,OCSPP. (2013, August 29). Colony Collapse Disorder | US EPA. US EPA. https://www.epa.gov/pollinator-protection/colony-collapse-disorder ‌ WWI helmets protected against shock waves as well as modern ones by Steffie Drucker WWI helmets protect against shock waves just as well as modern designs. (2020). EurekAlert! https://www.eurekalert.org/pub_releases/2020-02/du-whp021420.php  Op ‘t Eynde, J., Yu, A. W., Eckersley, C. P., & Bass, C. R. (2020). Primary blast wave protection in combat helmet design: A historical comparison between present day and World War I. PLOS ONE, 15(2), e0228802. https://doi.org/10.1371/journal.pone.0228802  Subscribe to Curiosity Daily to learn something new every day with Cody Gough and Ashley Hamer. You can also listen to our podcast as part of your Alexa Flash Briefing; Amazon smart speakers users, click/tap “enable” here: https://curiosity.im/podcast-flash-briefing

In our third episode, the HOPES podcast talks to Dr. Lisa Stanek, Senior Principal Scientist at Sanofi, about her Huntington's Disease research. Dr. Stanek's paper discussed in this episode can be found at: https://www.ncbi.nlm.nih.gov/pubmed/24484067. The music heard in today's episode was found on freemusicarchives and includes the following: “Carousel” by Johnny Ripper “I'm not here” by Johnny Ripper “(Untitled) waking up” by Johnny Ripper “On the moon” by Johnny Ripper “Error, inc” by Johnny Ripper

RNA Interference(RNAI) is set to pave the way for next gen Cancer treatments.  What is RNAI and why is it so special?  We brought an actual SCIENTIST on the show to explain just that.   Emily Jennings is a PhD candidate at the University of Cincinnati.  Her work has been featured in the UC Magazine, Live Science, WCPO NEWS and Science Newsline.  Find out more about her work at www.emgen.science. Follow Emily on Twitter @emgen_science.  

The sixth episode of Not A Hobby features Rahul Mitra. He was born in Hyderabad, India, and lives in Houston. His work is heavily drawing based - mostly black ink on paper - through which he’s created his own visual vocabulary. He sees his work much like notes and his drawings like an extension of his handwriting. Rahul is also a scientist. He is the program director at The Center for RNA Interference and Non-Coding RNAs at the MD Anderson Cancer Research Center in Houston. RNA, or ribonucleic acid, is one of the three major biological macromolecules that are essential for all known forms of life. They are the messenger between our DNA and the ability to produce proteins. A non-coding RNA is a RNA molecule that is not translating between DNA and protein production. So the idea is to introduce non-coding RNA into cells to disrupt production of particular proteins and whatever gene expression they trigger or suppress. Thus non-coding RNA can be targets to treat cancer. All of this is to say that Rahul is pretty with it - looking at things on such a molecular level, testing out theories that might never come to fruition and all the while looking at society as a whole understanding how external forces can influence us on the microscopic level.

Reading by Judy Lieberman, MD, PhD, author of Harnessing RNA Interference for Therapy: The Silent Treatment

Dr. Craig Mello won the Nobel Prize in 2006 for his work on "RNA interference." In this episode, Dr. Mello explains what he actually discovered to comedians Myq Kaplan, Jo Firestone, and Anna Drezen. Recorded in front of a live audience at the EcoTarium in Worcester, MA with help from SciCafeWoo. Hosted by Chris Duffy. 

Background: Signaling studies in cell lines are hampered by non-physiological alterations obtained in vitro. Physiologic primary tumor cells from patients with leukemia require passaging through immune-compromised mice for amplification. The aim was to enable molecular work in patients' ALL cells by establishing siRNA transfection into cells amplified in mice. Results: We established delivering siRNA into these cells without affecting cell viability. Knockdown of single or multiple genes reduced constitutive or induced protein expression accompanied by marked signaling alterations. Conclusion: Our novel technique allows using patient-derived tumor cells instead of cell lines for signaling studies in leukemia.

Integrating non-viral vectors based on transposable elements are widely used for genetically engineering mammalian cells in functional genomics and therapeutic gene transfer. For the Sleeping Beauty (SB) transposase system it was demonstrated that convergent transcription driven by the SB transposase inverted repeats (IRs) in eukaryotic cells occurs after somatic integration. This could lead to formation of double-stranded RNAs potentially presenting targets for the RNA interference (RNAi) machinery and subsequently resulting into silencing of the transgene. Therefore, we aimed at investigating transgene expression upon transposition under RNA interference knockdown conditions. To establish RNAi knockdown cell lines we took advantage of the P19 protein, which is derived from the tomato bushy stunt virus. P19 binds and inhibits 21 nucleotides long, small-interfering RNAs and was shown to sufficiently suppress RNAi. We found that transgene expression upon SB mediated transposition was enhanced, resulting into a 3.2-fold increased amount of colony forming units (CFU) after transposition. In contrast, if the transgene cassette is insulated from the influence of chromosomal position effects by the chicken-derived cHS4 insulating sequences or when applying the Forg Prince transposon system, that displays only negligible transcriptional activity, similar numbers of CFUs were obtained. In summary, we provide evidence for the first time that after somatic integration transposon derived transgene expression is regulated by the endogenous RNAi machinery. In the future this finding will help to further improve the molecular design of the SB transposase vector system.

A combination of functional and proteomics approaches identifies regulators of ERK signaling in Drosophila.

Background: The marine sponge Tethya wilhelma and the freshwater sponge Ephydatia muelleri are emerging model organisms to study evolution, gene regulation, development, and physiology in non-bilaterian animal systems. Thus far, functional methods (i.e., loss or gain of function) for these organisms have not been available. Results: We show that soaking developing freshwater sponges in double-stranded RNA and/or feeding marine and freshwater sponges bacteria expressing double-stranded RNA can lead to RNA interference and reduction of targeted transcript levels. These methods, first utilized in C. elegans, have been adapted for the development and feeding style of easily cultured marine and freshwater poriferans. We demonstrate phenotypic changes result from `knocking down' expression of the actin gene. Conclusion: This technique provides an easy, efficient loss-of-function manipulation for developmental and gene regulatory studies in these important non-bilaterian animals.

Efficient and safe protein nanoparticles for the targeted delivery of small molecule, protein and oligonucleotide based drugs will play a key role in the field of science in the upcoming years. Whereas viral and liposomal formulations have been extensively tested throughout the last two decades, their inherent and in the case of viruses sometimes even fatal obstacles not seldom seem impossible to conquer. The time for the development of a new therapeutic option in form of an advanced drug delivery system within pharmaceutical technology, biopharmacy and clinical studies has come. In our eyes gelatin based nanoparticles with polysaccharide and peptide modifications are an optimum to fulfil this need and will therefore be the center of the research presented in this work. Basically, nanoparticles with a size from 150 to 300 nm were prepared by desolvating a clear solution of gelatin through dropwise addition of an organic anti-solvent under heavy stirring. A subsequent destabilization of the water soluble protein chains resulted in round particles with a homogenous size distribution and an even surface. Initially, the polymers used for the formulation of the nanoparticles were characterized by such methods like asymmetric flow field-flow fractionation and nuclear magnetic resonance spectroscopy. Furthermore, established measurement and calculation algorithms were revised into state-of-the-art technology and applied as so called automatic microviscosimetry for in- depth protein analysis. The development of novel nanoparticle formulations based on these polymers was done in a second step using diethyl-amino-ethanol-dextran, polysorbate and polyethylene glycol, as well as methylation and acetylation chemistry. While the modified dextran mainly increased the zeta potential of the nanoparticles, the other modifications were intended to change the pharmacokinetic distribution patterns towards e.g. prolonged circulation times. In novel nanoparticle cytology science the use of a flow chamber device for cell cultivation allowed us to study the interaction patterns of nanoparticles with adherent cells under near to physiological conditions simulating blood vessels, junctions and shear stress. This in-vitro model can be used for online preclinical and high-throughput screenings of new nanoparticle and protein formulations with cell monolayers. The hindrances in traditional static cell culture models were shown to be overcome by comparing several nanoparticle formulations in a static and in a flow model. Proper nanoparticle formulations were tested further in innovative preclinical in-vivo models like the hamster dorsal skin fold chamber and the mouse cremaster model to elucidate their body distribution and targeting properties with a focus on kinetics, blood cell interaction and novel fluorescence detection techniques. In addition, the potential of gelatin nanoparticles as therapeutic options in a model for antigen induced arthritis was demonstrated. Finally, hybrid (sandwich) nanoparticles were formulated by combining gelatin nanoparticle preformulations with the endosomolytic peptide Melittin from bee venom and loading them with small interfering RNA molecules against VEGFR2 and luciferase. The novel hybrid carriers were extensively tested in cell cultures towards their efficiency to induce a protein knock-down based on RNA interference. With these results the door for further, more profound in-vivo studies in the field of oncology might be opened.

VI - Maturazione dell'mRNA e RNA catalitici VI-C) Applicazioni pratiche dei

VI - Maturazione dell'mRNA e RNA catalitici VI-B) Ribozimi ed RNA