Aptamer-Functionalized Lipid Nanoparticles for T-cell Mediated Delivery

Garrett Collett – Scientist, Product Sciences, Bristol Myers Squibb; Nataly Kacherovsky – Scientist, University of Washington; Suzie Pun – Washington Research Foundation Professor, Bioengineering, University of Washington

Introduction:

CAR T cell therapy offers breakthrough cancer treatment, yet manufacturing of virus for T cell engineering remains complex and costly [1]. Lipid nanoparticles (LNPs) provide a scalable non-viral alternative, but conventional formulations lack intrinsic cell targeting, relying on serum components (ApoE) for entry and restricting their utility for precision engineering [2]. We introduce a modular aptamer-functionalized LNP platform to address this challenge [3]. By functionalizing LNPs with DNA aptamers against specific T-cell markers, we demonstrate targeted delivery of mRNA and CRISPR payloads, enabling highly specific transfection of primary human T cells.