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
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
