Tech Session IV: Nanomedicine and Nanoscale Delivery (Focus: Gene)
Lipid-siRNA Organization Modulates the Intracellular Dynamics of Lipid Nanoparticles
Wednesday, July 16, 2025
3:16 PM - 3:27 PM EDT
Location: 120 B/C
Introduction: Lipid nanoparticles (LNPs) have demonstrated clinical success as delivery platforms for nucleic acids, including siRNA (Onpattro®, 2018), mRNA (COVID-19 vaccines, 2020), and CRISPR tools (Phase III trials, 2024). Despite these advances, the relationship between LNP structural organization and intracellular behavior, particularly before RNA release, remains poorly understood. This study investigates how lipid-siRNA organization influences key intracellular dynamics of LNP, including membrane fusion, cellular uptake, and endosomal escape, using porphyrin-lipid-based siRNA-LNPs as a model system.
Learning Objectives:
At the completion of this activity, participants will know
Understand how lipid-siRNA organization within LNPs influences key intracellular processes
Explain the use of cryo-EM and live-cell imaging in studying LNP structural-functional properties
Evaluate how N/P ratio adjustments influence LNP therapeutic performance and RNA delivery efficiency
Alexander Keszei, NA – Research Scientist, University Health Network; Shagun Kothari, NA – Graduate student, University of British Columbia; Heyi Liu, NA – Graduate student, University of Toronto; Anni Pan, NA – Research Scientist, University Health Network; Jihyun Kim, NA – Graduate student, University of Toronto; Jiachuan Bu, NA – Reasearch Scientist, University Health Network; Kamanzi Albert, NA – Postdoc, University of British Columbia; David Dai, NA – Graduate student, University of Toronto; Mohammad Mazhab-Jafari, NA – Professor, University of Toronto; Juan Chen, NA – Scientific Associate, University Health Network; Sabrina Leslie, NA – Professor, University of British Columbia; Gang Zheng, NA – Professor, University of Toronto
