04/20/2023
By Sanjeev Manohar
Thursday, April 20
3:30 - 4:30 p.m.
Shah Hall 310
Abstract:
Lipid nanoparticles (LNPs) have come to the forefront as the de facto industry standard for in vivo delivery of RNA medicines. This technology, originally developed with a focus on small interfering RNA (siRNA), relies on cationic or ioniozable lipid molecules and a substantial mass of excipient lipids to complex with the RNA phosphate backbone and drive assembly into nanoparticles. Despite many years of development and successful clinical application in COVID-19 vaccines, LNP technology still faces substantial hurdles in translation to widespread use across diverse applications. The large quantity of LNP delivery materials required per unit mass of RNA and their predisposition to inducing strong inflammatory responses may be acceptable for some vaccine applications, but will likely present a problem for therapeutic deployment of RNA, where larger doses must be safely delivered to target tissues by intravenous administration. To address these challenges, we have developed an alternative to conventional cationic lipid-based delivery systems using alkylamine branches linked together by a biodegradable polyester scaffold, creating a family of chemically defined, high molecular weight dendrimers and dendrons with greater gene delivery potency and safety characteristics compared to conventional LNPs. This approach enables a greater variety of potential applications for RNA therapeutics that can be safely administered systemically to deliver RNA payloads to various organ systems.
Bio:
Jasdave S. Chahal, Chief Scientist at Tiba Biotech, holds a B.Sc. with honors in Biopharmaceutical Science from the University of Ottawa, and a Ph.D. in molecular biology from Princeton University. He began his postdoctoral research in 2013 with Hidde Ploegh at the Whitehead Institute to focus on vaccinology and immunotherapy, initiating projects to engineer RNA molecules as vectors against infectious disease and cancer. His published work demonstrated the effectiveness of these synthetic RNA payloads delivered with dendritic nanomaterials against viral and complex parasitic diseases in animal models. He transitioned to the Massachusetts Institute of Technology’s Koch Institute for Integrative Cancer Research in 2016 to further refine the technology before co-founding Tiba. Jasdave leads R&D activities at the company, advancing a range of academic and government collaborations.