<i>In vivo</i> base editing of Angptl3 via lipid nanoparticles to treat cardiovascular disease.

ABSTRACT: Cardiovascular disease (CVD) is the leading cause of death globally and is exacerbated by elevated blood levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs). Existing approaches for decreasing blood lipid levels rely on daily medications, leading to poor patient adherence. Gene therapy represents a promising "one and done" strategy to durably reduce blood lipid levels. ANGPTL3 has emerged as a potential target for gene therapy, as naturally occurring loss-of-function variants are cardioprotective. Here, we use lipid nanoparticles to package and deliver CRISPR adenine base editors (ABEs), which enable gene knockout without requiring potentially harmful DNA double-strand breaks. We package ABE mRNA and a synthetic guide RNA targeted to disrupt an important sp

SUBMITTER: Khirallah J 

PROVIDER: S-EPMC11932681 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature