Evaluating the state of the science for adeno-associated virus integration: An integrated perspective.
Level 5 - mechanism / opinion, no new human data
Narrative review and expert roundtable white paper without original human data or systematic review methodology
PubMed 35690906 · doi:10.1016/j.ymthe.2022.06.004
What was done
This white paper summarizes discussions from a virtual roundtable hosted by the American Society of Gene and Cell Therapy (ASGCT) on August 18, 2021. Preclinical and clinical experts reviewed evidence of recombinant adeno-associated virus (rAAV) host genome integration, risks of insertional mutagenesis in patients, technical considerations, regulatory guidance, and bioethics.
What was found
No numerical data or rates are reported in the abstract. Most rAAV DNA remains episomal, though low-frequency genomic integration occurs. Although rAAV insertional mutagenesis has caused tumorigenesis in a small number of neonatal mouse studies, oncogenesis risk in humans remains theoretical with no confirmed genotoxic events reported to date.
Why it matters
As rAAV gene therapies expand clinically, this paper contextualizes theoretical genotoxicity and insertional mutagenesis risks to inform research design, regulatory policy, and patient care.
Limits
This is a narrative expert review rather than a systematic review. The abstract provides no quantitative integration frequencies. Tumorigenesis data are derived entirely from preclinical neonatal mouse models, and true human clinical risk remains theoretical and unquantified.
Cited by
- supports Adeno-associated virus (AAV) vector DNA does not integrate into human chromosomes in over 90% of cases, instead forming an episome.