Introduction: Although Lipid Nanoparticles (LNPs) have become a powerful and approved platform for nucleic acid delivery, it is limited by poor endosomal escape (≤5%). Despite its advances, currently no approved LNP formulation is available towards the cure for HIV. Compared to adenovirus-based therapeutic systems, that recently failed at clinical setting for HIV cure, LNPs with specific targeting and high endosomal escape can be a promising alternative. Herein, disulfide-based ionizable lipid-based LNPs were developed that has improved cytosolic delivery of CRISPR guide RNAs in primary macrophages.
Learning Objectives:
describe the challenges of endosomal escape in LNP-mediated nucleic acid delivery.
demonstrate BA-LNP’s enhanced endosomal escape and application in HIV cure strategy.
