From one-size-fits-all to on-demand: personalized crispr gene editing for rare genetic liver diseases - 02/08/26
Highlights |
• | CRISPR gene editing has entered clinical trials for multiple genetic liver diseases. |
• | Personalized patient-specific CRISPR therapy was first delivered in 2025. |
• | LNP delivery systems enable non-viral hepatocyte-targeted gene correction. |
• | Base and prime editors enable nucleotide-precision without double-strand breaks. |
• | Regulatory frameworks are evolving to accommodate bespoke genetic therapies. |
Abstract |
Rare genetic liver diseases collectively affect millions of individuals worldwide and encompass a heterogeneous group of monogenic disorders including Wilson disease, alpha-1 antitrypsin deficiency, glycogen storage diseases, urea cycle disorders, progressive familial intrahepatic cholestasis, and acute hepatic porphyrias. While conventional management relies on dietary modification, pharmacotherapy, and ultimately liver transplantation, the advent of clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing has opened transformative therapeutic avenues. This review provides a comprehensive and critical appraisal of the current landscape of CRISPR-based therapies for genetic liver diseases, from preclinical proof-of-concept studies to landmark clinical trials. We examine the evolution from conventional Cas9 nuclease-mediated editing to precision tools including base editors and prime editors, which enable single-nucleotide corrections without inducing double-strand DNA breaks. The role of lipid nanoparticle delivery systems in achieving efficient hepatocyte-targeted delivery is discussed, alongside emerging challenges in pediatric dosing and immunogenicity. We highlight the paradigm shift toward personalized, patient-specific CRISPR therapies, exemplified by the first-in-human bespoke gene editing treatment delivered in 2025. Competing nucleic acid technologies, including RNA interference and antisense oligonucleotides, are compared in terms of durability, safety, and cost-effectiveness. Finally, we critically evaluate the evolving regulatory landscape and propose a priority framework for selecting genetic liver diseases most amenable to CRISPR-based correction. This review underscores that CRISPR gene editing is transitioning from experimental promise to clinical reality for genetic liver diseases, with personalized approaches poised to redefine the treatment paradigm.
Le texte complet de cet article est disponible en PDF.Keywords : CRISPR, Gene editing, Genetic liver disease, Lipid nanoparticles, Base editing, Personalized medicine, Gene therapy
Plan
Vol 50 - N° 8
Article 102892- octobre 2026 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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