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Mouse model could help identify viral vectors that may cause tumors

Modified viruses used to deliver genetic material into cells, known as viral vectors, have become the go-to delivery capsule in gene therapy. Capitalizing on their viral nature, investigators use viral vectors to efficiently target certain cells and deliver genetic material into the cell nucleus where native genes reside.

Viral vectors from recombinant adeno-associated virus (rAAV) are favored gene transfer systems for human clinical trials because of their safe track record in human clinical trials. In fact, the first gene therapy drug, approved in Europe, treats a rare disease that disrupts fat production in the body and is based on the recombinant adeno-associated virus platform. Still, a few reports have surfaced suggested that some rAAV vectors may cause DNA mutations in a host, with results showing excess liver tumors in mice.

"While preclinical studies have overwhelmingly supported the safety of rAAV treatment in numerous different tissues and animal models, even a small fraction of vector integration in a tissue as large as a human liver could create many tumor-promoting mutations," says Douglas M. McCarty, PhD principal investigator in the Center for Gene Therapy at The Research Institute at Nationwide Children's Hospital and lead study author.

"The studies in mice that showed genotoxicity suggest that specific features of certain rAAV vector constructs may encourage liver tumor formation rather than rAAV vector treatments in general."
 
 

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