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REVIEW article

Front. Genome Ed.
Sec. Genome Editing in Human Health and Disease
Volume 6 - 2024 | doi: 10.3389/fgeed.2024.1458037
This article is part of the Research Topic In vivo Therapeutic Approaches Based on Liver-Targeted Genome Editing View all articles

In vivo liver targeted genome editing as therapeutic approach: progresses and challenges

Provisionally accepted
Chiara Simoni Chiara Simoni 1,2Elena Barbon Elena Barbon 1*Andrés F. Muro Andrés F. Muro 3Alessio Cantore Alessio Cantore 1,2
  • 1 San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Milan, Italy
  • 2 Vita-Salute San Raffaele University, Milan, Lombardy, Italy
  • 3 International Center for Genetic Engineering and Biotechnology, Trieste, Friuli-Venezia Giulia, Italy

The final, formatted version of the article will be published soon.

    The liver is an essential organ of the body that performs several vital functions, including the metabolism of biomolecules, foreign substances, and toxins, and the production of plasma proteins, such as coagulation factors. There are hundreds of genetic disorders affecting liver functions and, for many of them, the only curative option is orthotopic liver transplantation, which nevertheless entails many risks and long-term complications. Some peculiar features of the liver, such as its large blood flow supply and the tolerogenic immune environment, make it an attractive target for in vivo gene therapy approaches. In recent years, several genome-editing tools mainly based on the clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9) system have been successfully exploited in the context of liver-directed preclinical or clinical therapeutic applications. These include gene knock-out, knock-in, activation, interference, or base and prime editing approaches. Despite many achievements, important challenges still need to be addressed to broaden clinical applications, such as the optimization of the delivery methods, the improvement of the editing efficiency, and the risk of on-target or off-target unwanted effects and chromosomal rearrangements. In this review, we highlight the latest progress in the development of in vivo liver-targeted genome editing approaches for the treatment of genetic disorders. We describe the technological advancements that are currently under investigation, the challenges to overcome for clinical applicability, and the future perspectives of this technology.

    Keywords: Liver, Genome editing, Liver directed genome editing, Delivery methods, Lipid nano particle

    Received: 01 Jul 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Simoni, Barbon, Muro and Cantore. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Elena Barbon, San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Milan, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.