In vivo delivery strategies for therapeutic CRISPR genome editing

Authors

• Leonardo Martin, University of University of Antwerp, Belgium Belgium
• Jure Bohinc, University of Antwerp, Belgium
• Alessandra Recchia, University of Ljubljana, Slovenia
• Stefano Gritti, University College London,UK
• Giorgia Santilli, University of University of Antwerp, Belgium Belgium
• Joanna Zeyland, University of Ljubljana, Slovenia
• Melita Vidaković, University of University of Antwerp, Belgium Belgium
• Nevena Grdović, University of Ljubljana, Slovenia
• Karim Benabdellah, University of Ljubljana, Slovenia
• shariqa khawaja, Aga Khan UniversityFollow

Document Type

Article

Department

Centre for Regenerative Medicine and Stem Cell Research

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.

Comments

Pagination is not provided by author/publisher.

Publication (Name of Journal)

International Journal of Biological Sciences

DOI

10.7150/ijbs.133162

Recommended Citation

Martin, L., Bohinc, J., Recchia, A., Gritti, S., Santilli, G., Zeyland, J., Vidaković, M., Grdović, N., Benabdellah, K., khawaja, s. (2026). In vivo delivery strategies for therapeutic CRISPR genome editing. International Journal of Biological Sciences, 22(12).
Available at: https://ecommons.aku.edu/crm/89