First-in-Human CRISPR-Cas9 Editing of ANGPTL3 Shows Dose‑Dependent Protein Knockdown with Acceptable Short‑Term Safety in Phase 1 Trial

Highlights

– CTX310, a lipid-nanoparticle (LNP) delivery of CRISPR-Cas9 mRNA and guide RNA targeting hepatic ANGPTL3, was administered as a single IV dose to 15 adults with refractory dyslipidemia in an ascending‑dose phase 1 trial.

– No dose‑limiting toxicities were attributed to CTX310. Dose‑dependent reductions in circulating ANGPTL3 were observed at doses ≥0.6 mg/kg, with mean reductions of ~33% at 0.6 mg/kg and ~74–80% at 0.7–0.8 mg/kg.

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