{"id":"doi:10.1177/01926233261448135","kind":"review","title":"Adeno-Associated Virus Gene Therapy: Is There a Risk of Insertional Mutagenesis?","authors":["Batty P"],"author_count":1,"year":2026,"published":"2026-05-31","venue":"Toxicologic pathology","cited_by":1,"doi":"10.1177/01926233261448135","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1177/01926233261448135","archive_url":"https://space-kitty.com/papers/doi:10.1177/01926233261448135","updated":null,"pmid":"42218611","pmcid":"PMC13478430","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13478430/pdf","abstract":"Adeno-associated virus (AAV) gene therapy has received approvals for the treatment of a number of rare monogenic disorders. There are questions surrounding the natural history of recombinant AAV (rAAV) vectors, which could provide insights into durability and long-term safety. Wild-type AAV (wtAAV) persists in extrachromosomal episomes and is also able to actively or passively integrate into the host genome. Although clonal wtAAV integration has been described in a small number of hepatocellular carcinoma cases, this at most represents a minor risk factor. Differences in the structure of wtAAV and rAAV limit translation of these studies. Recombinant AAV also persists in episomal forms with a small proportion becoming integrated. Some early murine studies demonstrated insertional mutagenesis after treatment with rAAV. These findings have not consistently been seen and are likely context-dependent (high-dose or neonatal treatment). There have been no reports of rAAV insertional mutagenesis in large animal models or human biopsy samples.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Adeno-Associated Virus Gene Therapy: Is There a Risk of Insertional Mutagenesis?\" by Batty P, https://doi.org/10.1177/01926233261448135, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-cell-therapy","name":"Gene & Cell Therapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}