Drug delivery systems for CRISPR-based genome editors

• Published in: Nature reviews. Drug discovery Vol. 22; no. 11; pp. 875 - 894
• Main Authors: Madigan, Victoria, Zhang, Feng, Dahlman, James E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2023; Nature Publishing Group
• Subjects: 631/61/391; 639/166/985; Animals; Antigens; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer Research; Clinical trials; CRISPR; CRISPR-Cas Systems - genetics; Drug Delivery Systems; Drugs; Gene Editing; Gene Transfer Techniques; Genes; Genetic engineering; Genome editing; Genomes; Medicinal Chemistry; Molecular Medicine; Nanoparticles; Pharmacology/Toxicology; Proteins; Proteins - genetics; Review Article; RNA polymerase; Viruses
• ISSN: 1474-1776; 1474-1784
• DOI: 10.1038/s41573-023-00762-x

CRISPR-based drugs can theoretically manipulate any genetic target. In practice, however, these drugs must enter the desired cell without eliciting an unwanted immune response, so a delivery system is often required. Here, we review drug delivery systems for CRISPR-based genome editors, focusing on adeno-associated viruses and lipid nanoparticles. After describing how these systems are engineered and their subsequent characterization in preclinical animal models, we highlight data from recent clinical trials. Preclinical targeting mediated by polymers, proteins, including virus-like particles, and other vehicles that may deliver CRISPR systems in the future is also discussed. CRISPR-based genome editing has the potential to treat many human genetic diseases, but achieving stable, efficient and safe in vivo delivery remains a challenge. This Review assesses current delivery systems for genome editors—focusing on adeno-associated viruses and lipid nanoparticles—and highlights data from recent clinical trials. Emerging delivery systems and ongoing challenges in the field are discussed.