To Target or Not to Target:
Lessons from RNAi-Based Targeted Lipid Nanoparticles
Original Broadcast: Thursday, October 5th at 11:00 a.m. CDT
Access Webinar On-Demand
About the Webinar
In this webinar you will learn about the misconceptions, challenges, and controversies in targeting using lipid nanoparticles. Dan Peer, Ph.D., explains how to target leukocytes for RNAi therapy in inflammatory bowel disease and mantle cell lymphoma, the potential of GAGomer technology, and the targeted delivery of siRNA to treat glioblastoma.
About the Speaker
Dan Peer, Professor, Department of Cell Research & Immunology, Tel Aviv University
Dan Peer is a principal investigator and a senior lecturer who leads an NIH-funded laboratory at Tel Aviv University. Dan received his education in Biochemistry and Biophysics from Tel Aviv University, Israel. From January 2005 to August 2008, he worked at Harvard Medical School, where he still holds a visiting scientist appointment. He joined the Department of Cell Research & Immunology, in the Faculty of life sciences at Tel Aviv University in September 2008 to establish the laboratory of Nanomedicine. Dan’s research was among the first to demonstrate systemic delivery of RNAi using targeted nano-carriers to the immune system and the first to utilise RNAi for in-vivo validation of new drug targets within the immune system. His current interests include the generation of novel platforms for delivery of RNAi payloads into specific cell types and the utilization of these nanocarriers for in vivo discovery and validation of new drug targets. In addition, he is active in understanding the immuno-toxicity of novel RNAi formulations. He is the editor of the new title “Handbook of Harnessing Biomaterials for Nanomedicine”, published in 2011, an associate editor of the journal of biomedical nanotechnology and on the editorial board of the journals Nanotechnology of the institute of Physics in the UK, and the Journal of Controlled Release. Dan received more than 20 awards and honours (partial list): He is a Marie Curie Fellow of the European Union, An Alon Fellow, and received the Pfizer Award in Drug Discovery and Delivery. He also received the 2010 Innovator Award from the Kenneth Rainin Foundation. He is the inventor and co-inventor of more than 30 patents (both granted and pending). He is also a co-founder of ORUUS Pharma and Quiet Therapeutics that were founded based on his work and aim to bring the area of personalized medicine utilizing nanotechnology into the clinic.
I have read that hydrophobic ligands like folate tend to associate with nanoparticle surface and have limited availability to bind to receptors (if particle is hydrophobic). How can you work around this?
Thanks for your question, Andrew. Indeed, this can be problematic for hydrophobic particles. With respect to lipid nanoparticles, the more prevailing strategy to get around this issue is to present PEG chains of a suitable length at appropriate densities to effectively increase the hydrophilicity of the particle. When carefully tuning these parameters, in combination with the ligand density (i.e. surface concentration), these effects can be minimized, especially if the targeting moiety (e.g. folate as you suggested) is presented at the distal end of the PEG chain. This would effectively limit its re-adsorption to the nanoparticle surface. Alternatively, others have leveraged formulations that effectively "shed" their PEG after administration (especially when PEG is detrimental to uptake) in order to reveal the targeting moiety presented directly at the surface (say, a cell penetrating peptide). Of course, one must carefully tune the amount of ligand presented on the surface (i.e. concentration) in order to circumvent the issue you mentioned, and still achieve effective uptake.