Programmable Genome-Editing Technologies as Single-Course Therapeutics for Atherosclerotic Cardiovascular Disease

Curr Atheroscler Rep. 2022 Nov;24(11):861-866. doi: 10.1007/s11883-022-01063-1. Epub 2022 Aug 22.

Abstract

Purpose of review: To establish genome editing as a promising therapeutic approach for the treatment and prevention of atherosclerotic cardiovascular disease.

Recent findings: Systemic delivery of a CRISPR adenine base editor using lipid nanoparticles demonstrated a near 90% reduction in circulating PCSK9 and over 60% reduction in blood LDL-C in nonhuman primates with the effects remaining durable at least 8 months following a single course. Preclinical proof-of-concept studies have elucidated the superior therapeutic potential of genome-editing approaches for the treatment of hyperlipidemia, thus substantiating their progression to clinical studies.

Keywords: Atherosclerotic cardiovascular disease; CRISPR/Cas9; Genome editing; High cholesterol; Hyperlipidemia; One-and-done therapy.

Publication types

  • Review

MeSH terms

  • Adenine
  • Animals
  • Atherosclerosis* / genetics
  • Atherosclerosis* / therapy
  • CRISPR-Cas Systems
  • Cardiovascular Diseases* / genetics
  • Cardiovascular Diseases* / therapy
  • Cholesterol, LDL
  • Gene Editing
  • Humans
  • Liposomes
  • Nanoparticles
  • Proprotein Convertase 9 / genetics

Substances

  • Cholesterol, LDL
  • Lipid Nanoparticles
  • Liposomes
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Adenine