Isoprenoid CARTs: <i>In Vitro</i> and <i>In Vivo</i> mRNA Delivery by Charge-Altering Releasable Transporters Functionalized with Archaea-inspired Branched Lipids.

ABSTRACT: The delivery of oligonucleotides across biological barriers is a challenge of unsurpassed significance at the interface of materials science and medicine, with emerging clinical utility in prophylactic and therapeutic vaccinations, immunotherapies, genome editing, and cell rejuvenation. Here, we address the role of readily available branched lipids in the design, synthesis, and evaluation of isoprenoid charge-altering releasable transporters (CARTs), a pH-responsive oligomeric nanoparticle delivery system for RNA. Systematic variation of the lipid block reveals an emergent relationship between the lipid block and the neutralization kinetics of the polycationic block. Unexpectedly, iA21A11, a CART with the smallest lipid side chain, isoamyl-, was identified as the lead isoprenoid CART for t

SUBMITTER: Rahn HP 

PROVIDER: S-EPMC12410861 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature