VL422 is an ionizable cationic lipid employed in the development of lipid nanoparticles (LNPs) for delivering CRISPR single-guide RNA (sgRNA) and Cas9 mRNA for gene editing both in vitro and in vivo. LNPs formulated with VL422 and encapsulating Cas9 mRNA and sgRNA targeting the gene for angiopoietin-related protein 3 (ANGPTL3) induce the deletion of a premature stop codon in ANGPTL3 in the livers of cynomolgus monkeys. Loss-of-function of ANGPTL3 is associated with reduced plasma levels of LDL, HDL, and cholesterol.
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