News Release

Gene therapy-associated cancer incidence depends on vector design

Peer-Reviewed Publication

JCI Journals

Gene therapy is a promising strategy to correct hereditary disorders. The approach takes advantage of viral vectors to deliver a corrected version of the mutated gene. Adeno-associated virus (AAV) has many features that make it a favorable vector for gene therapy. In animal models, AAV-mediated gene delivery is generally regarded as safe and has demonstrated efficacy for some genetic diseases. However, a recent study reported an increase in liver cancer in mice after AAV gene therapy. A new publication in the Journal of Clinical Investigation reveals that AAV vector design influences the likelihood of developing cancer in the liver. Charles Venditti and colleagues at the National Institutes of Health looked for the development of hepatocellular carcinoma (HCC) in a large number of mice that had received AAV gene therapy. HCC was associated with the AAV vector integrating within a specific site in the genome and inducing expression of microRNAs and a retrotranposon. Moreover, AAV dose, the choice of enhancer/promoter, and timing of delivery all influenced the HCC incidence. The results of this study provide insight into features that should be considered when designing AAV vectors for gene therapy.



Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy


Charles Venditti
National Institutes of Health, Bethesda, MD, USA
Phone: 301-496-6213; Fax: 301-451-3853; E-mail:

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