Gene therapy and genome editing for lipoprotein disorders.

Journal: European heart journal
Published Date: Jul 2, 2025

Abstract

Genetic factors play a critical role in the development of lipoprotein disorders, which significantly contribute to atherosclerotic cardiovascular disease (ASCVD). Traditional management of these conditions has relied on lipid-lowering therapies, which require lifelong adherence. Recent advancements in gene addition and editing technologies offer novel and potentially transformative approaches for treating lipoprotein disorders by targeting the relevant genetic pathways for each disease. This review revisits major monogenic and polygenic disorders of lipoprotein metabolism, including familial hypercholesterolemia, elevated lipoprotein(a), and familial chylomicronemia syndrome, and discusses the genetic-based therapies for management. RNA-based, gene addition and gene editing therapies, including Clustered Regularly Interspaced Short Palindromic Repeats, base editing and interventions whereby, are highlighted for their potential to provide durable treatments which overcome the adherence challenge. Integration of machine learning for risk prediction and the use of polygenic risk scores to enhance risk stratification further demonstrate the promise of personalized approaches, and overall potential for gene-based treatments to revolutionize ASCVD prevention and management.

Authors

  • Chen Gurevitz
    Metabolism and Lipids Program, Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY 10029, USA.
  • Archna Bajaj
    Division of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, PA, USA.
  • Amit V Khera
    Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Ron Do
    The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Heribert Schunkert
    Deutsches Herzzentrum München, Technische Universität München, München, Germany.
  • Kiran Musunuru
    Division of Cardiovascular Medicine, Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.
  • Robert S Rosenson
    Cardiometabolics Unit, Mount Sinai Hospital, Mount Sinai Heart, NY, United States of America.

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