# Adeno-Associated Virus Gene Therapy: Is There a Risk of Insertional Mutagenesis?

Review · Batty P

- Archive id: doi:10.1177/01926233261448135
- Published: 2026-05-31
- Venue: Toxicologic pathology
- DOI: https://doi.org/10.1177/01926233261448135
- PMID: 42218611
- PMCID: PMC13478430
- Citations: 1
- Source URL: https://doi.org/10.1177/01926233261448135
- PDF: https://europepmc.org/articles/PMC13478430/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Gene & Cell Therapy](https://space-kitty.com/topics/gene-cell-therapy)

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