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Gene Delivery and Gene Editing (Focus Group - GDGE)

(195) Layered Lipid Nanoparticles for Ovarian Tumor-Targeted Gene Delivery

Introduction:

Though lipid nanoparticles (LNPs) are potent delivery vehicles for nucleic acids, extrahepatic NP delivery is limited by off-target uptake, surface opsonization, and immune clearance. NP surface modification is a powerful approach to address these challenges.

In this work, we demonstrate the transfection and targeting of layered LNPs (LLNP), or LNPs electrostatically-coated with polyanions [1]. Surface chemistry drives targeted uptake and impacts LNP biodistribution in vivo, greatly advantaging targeted gene delivery [2]. LLNP targeting is further used to target ovarian cancer tumors.

Learning Objectives:

  • Describe LNP electrostatic modification as a highly modular, tunable method to achieve targeting
  • Describe layered LNP uptake and transfection at organ- and cellular scales, based on outer polymer
  • Show polypeptide-coated LLNPs boost transfection in ovarian cancer lines and tumor tissue in vivo