Oxidized mRNA Lipid Nanoparticles for <i>In Situ</i> Chimeric Antigen Receptor Monocyte Engineering.

ABSTRACT: Chimeric antigen receptor (CAR) monocyte and macrophage therapies are promising solid tumor immunotherapies that can overcome the challenges facing conventional CAR T cell therapy. mRNA lipid nanoparticles (mRNA-LNPs) offer a viable platform for in situ engineering of CAR monocytes with transient and tunable CAR expression to reduce off-tumor toxicity and streamline cell manufacturing. However, identifying LNPs with monocyte tropism and intracellular delivery potency is difficult using traditional screening techniques. Here, ionizable lipid design and high-throughput in vivo screening are utilized to identify a new class of oxidized LNPs with innate tropism and mRNA delivery to monocytes. A library of oxidized (oLNPs) and unoxidized LNPs (uLNPs) is synthesized to evaluate mRN

SUBMITTER: Mukalel AJ 

PROVIDER: S-EPMC11611297 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature