Kara Gentry
BME PhD Proposal Presentation

Date: 2025-09-03
Time: 11:00 AM- 12:00PM
Location / Meeting Link: HSRB II, N600;

Committee Members:
James Dahlman, PhD (Advisor); Hyejin Kim, PhD; Hanjoong Jo, PhD; Wilbur Lam, MD/PhD; M.G. Finn, PhD


Title: Development of Lipid Nanoparticles for RNA Delivery to T cells in the Spleen

Abstract:
Recent advances in T cell gene therapy have accelerated the need for potent T cell delivery vehicles. Lipid nanoparticles (LNPs) have been used to deliver FDA-approved therapies to immune cells intramuscularly (e.g., SPIKEVAX, COMIRNATY) and to liver cells intravenously (e.g., ONPATTRO). However, delivery of LNPs to T cells in the spleen has proved challenging for two reasons. First, LNPs are readily cleared by the liver after systemic administration. Second, sufficient T cell transfection traditionally requires protein-conjugated LNPs to be administered at high doses. In this work, I aim to i) develop methods to decrease delivery to the liver, ii) increase delivery to T cells in the spleen at low doses, and iii) test T cell vehicles in preclinical models. I do so by employing glycolipids to detarget the liver and using DNA barcoding to screen potent ionizable lipids to identify T cell tropic LNPs. Finally, I will test these vehicles in non-human primates (NHPs) and understand species-dependent delivery differences.