In vivo delivery strategies for therapeutic CRISPR genome editing

Creative Commons License

Martin L., Bohinc J., Recchia A., Gritti S., Santilli G., Zeyland J., ...Daha Fazla

International journal of biological sciences, cilt.22, sa.12, ss.6539-6581, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 22 Sayı: 12
  • Basım Tarihi: 2026
  • Doi Numarası: 10.7150/ijbs.133162
  • Dergi Adı: International journal of biological sciences
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Directory of Open Access Journals, Zoological Record, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest)
  • Sayfa Sayıları: ss.6539-6581
  • Anahtar Kelimeler: base editing, CRISPR delivery systems, in vivo genome editing, lipid nanoparticles, organ-specific gene therapy, prime editing, viral vectors
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Akdeniz Üniversitesi Adresli: Evet

Özet

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.