Joel Hornby: | Hi everyone. Welcome to this Cambridge Healthtech Institute podcast for the upcoming Emerging Oligonucleotide Therapeutics, taking place this September 27th to the 28th at Discovery On Target in Boston. My name is Joel Hornby. I am a Conference Director for Cambridge Healthtech Institute. Today, I have the pleasure of interviewing our Chair and Speaker for Emerging Oligonucleotide Therapeutics, Professor Dan Peer, Director of the Laboratory of Precision NanoMedicine at Tel Aviv University. Dan, thank you for joining us. |
Dan Peer: | Thank you for having me. |
Joel Hornby: | Dan, a large focus of your research involves trying to figure out how to deliver RNA molecules into specific target tissues, especially leukocytes, via systemic administration. Could you please tell us a little bit more about this, and what the potential benefits may be? |
Dan Peer: | Well, I think the potential benefits are huge. If we can manipulate the function of leukocytes, the potential cure or disease management in different types of diseases, from hematological malignancies to inflammation, viral infection, rare genetic diseases, et cetera, will be huge, and I think that it's usually ... it's becoming more and more challenging, but I think leukocytes are one of the most difficult to transfect cells, so in our lab what we're trying to do is to create strategies that will specifically go to subsets of leukocytes in a very efficient manner and deliver those payloads, such as RNAi ... but not only RNAi, other nucleic acids as well, and try to manipulate their fates both again in different diseases, such as hematological malignancies ... for example, multiple myeloma, mantle cell lymphoma, chronic lymphocytic leukemia, and during inflammatory bowel diseases, we're also working on lymphocytes, that are influential there, and mononuclear phagocytes. These are the two major topics that we are trying to target our nanoparticles to those subsets of cells |
Joel Hornby: | I hear it's also pretty tricky, working with RNA, as it's so easily degraded. How do you cope with this particular challenge? |
Dan Peer: | So these days, already there are certain chemical modifications that stabilizes the RNA molecule so we have less of a problem. However, we still have problem with immune recognition, so RNA molecules could be recognized by different immune cells, and this is a paradox. We're trying to manipulate their fate, but at the same times we do not want it to be recognized as viruses trying to penetrate into those cells, so this is the tricky point. We are trying to cope with this issue by entrapping the RNA molecule in very sophisticated types of lipids that are called ionizable lipids and we charge them ... we're playing around with the pH, you know that to charge them in low pH and then change the pH to physiological pH, and therefore we get the particles uniform, homogeneous particles, that we can then coat with relevant ligands in order to target them to different subsets of leukocytes. |
Joel Hornby: | I understand you've begun to employ CRISPR-based gene editing in your research. Have you seen much success with this approach? |
Dan Peer: | Well, I would say that unfortunately, I think that we're still in the middle of the hype ... I haven't seen very clear data that we can give systemically, except to the liver and go to other subtypes in a very efficient manner, and use CRISPR to gene edit or other method to gene edit the genome, so we're still working on this area of genetics. We do think we are getting there, but I still think it's a bit early to further discuss this. I think we need to learn a little bit more and to see how we can stabilize, basically, the guided RNA and other molecules that we trap. |
Joel Hornby: | There seems to be growing interest in the potential clinical applications for lipid-based nanoparticles and extracellular vesicles in recent years. Why do you think that is, and where do you think the important research opportunities are now? |
Dan Peer: | Well I think that everyone wants to go beyond the liver, and right now, all the lipid and nanoparticles, all the liposome strategy, are all going to the liver, which is very good if you're working with liver diseases, but if you want to go beyond the liver, for example, solid tumors that are not in the liver, or you want to go after other diseases ... neurodegenerative diseases. Or you want to go after immune disease or inflammation in general, you need to be able to target those molecules not to the liver. Or even in the first stop to the liver, hopefully not to stay there. And this is a very tricky situation, because basically one needs to really try and bypass this. And this is not a trivial task, as I mentioned, but we and others are really developing interesting strategies that we believe will go, hopefully, in a reasonable time into the clinics for testing those strategies. |
Joel Hornby: | And Dan, so you're coming over to Boston for Emerging Oligonucleotide Therapeutics, at Discovery on Target this September, the 27th to the 28th. What are you looking forward to gaining there? |
Dan Peer: | So I think it's gonna be a very exciting event, because basically we're gonna hear what's going on, both in the clinic and in some labs, how companies are gonna deal with those challenges, and where we're standing with gene-editing, using CRISPR and other strategies. This is a very exciting time. I strongly believe that the nucleic acid therapeutics will gain more and more weight the next five to ten years. And personally I think that we are witnessing what happened with the protein therapeutics about 20 years ago, where it starts in clinical trials that are not really great, but in time, companies learn how to scale up, how to monitor, how to uniform and how to probe efficacy with therapeutic proteins, such as microantibodies. I strongly believe that in the oligonucleotides fields, including RNA and RNAi, this is something we will witness in the next five to ten years. It's really amazing how much progress we have made from 2002, 2003, when the first papers came showing the potential of RNAi molecules to silence gene mammalian cells, then show proof of concept in animal models. It really, really went very far, and remember that there are now few companies that are doing quite a lot of clinical trials. I'm gonna mention only one of them, because I think that they're the most advanced one, which is Alnylam in Boston. And really it's amazing that they have eight programs in clinical trials and one of them in Phase III, so I really think that many others will join in different types, not only RNAi, but also messenger RNA, which is gaining a lot of interest, and CRISPR, of course, and other methods to edit the genome. |
Joel Hornby: | Thank you very much for your time and expert insights today. |
Dan Peer: | Thank you. |
Joel Hornby: | Professor Dan Peer, Director of the Laboratory of Precision NanoMedicine at Tel Aviv University, will be speaking on Emerging Oligonucleotide Therapeutics at Discovery on Target, this September 27th to the 28th at the Westin Copley Place, Boston. If you'd like to hear Dan speak in person, go to www.discoveryontarget.com where you can register, entering the KeyCode "podcast", and where you'll also be able to see many other exciting talks, tracks, and features planned for this year's Discovery on Target. Once again, I'm Joel Hornby, from Cambridge Healthtech Institute. Thank you for listening. |