In vivo delivery strategies for therapeutic CRISPR genome editing.

Authors

Leonardo Martin, Jure Bohinc, Alessandra Recchia, Stefano Gritti, Giorgia Santilli, Joanna Zeyland, Melita Vidaković, Nevena Grdović, Karim Benabdellah, María Ortiz-Bueno, Bilge Debelec Butuner, Luana Pisaniello, Roberta Stilhano, Daniela Benati, Fatma Zehra Hapil, Shariqa Khawaja, Rajeevkumar Raveendran Nair, Carla Giacomelli, Erden Atilla, Federica Zinghirino, Tommaso Ferrari, Federico Corradi, Tamas J Laufer, Denis Khnykin, Gloria González Aseguinolaza, Mojca Skrbinek, Tjaša Mlakar, Tjaša Lapanja, Duško Lainšček

Published in

International journal of biological sciences. Volume 22. Issue 12. Pages 6539-6581. Epub Jul 11, 2026.

Abstract

CRISPR-based genome and epigenome editing technologies have rapidly evolved from programmable nucleases into a diverse therapeutic toolbox encompassing conventional CRISPR systems, base editing, prime editing, RNA targeting, and epigenetic modulation. While early clinical successes relied on ex vivo manipulation of patient-derived cells, recent advances in delivery chemistry and vector engineering are enabling direct in vivo editing across multiple organs. Here, we provide a comprehensive review of delivery modalities of CRISPR systems solely in vivo that underpin their therapeutic translation. We examine how anatomical, cellular, and immunological constraints shape organ-specific editing strategies in different organ systems and we highlight key preclinical and clinical milestones that define the current translational landscape. Across indications, delivery remains a critical determinant of efficacy, safety, and scalability, governing editor exposure, tissue selectivity, and risk of unintended genomic or epigenomic perturbation. This review, authored by members of the COST Action Genome Editing to treat Human Diseases (GenE-HumDi) Network, delineates the principles guiding in vivo genome and epigenome editing and outlines the remaining barriers to durable, tissue-selective, and broadly deployable CRISPR therapeutics.

PMID:
42524609
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.

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