New studies refocus attention on the genotoxicity of AAV vectors in gene therapy

Credit: © 2017, Mary Ann Liebert, Inc.

New Rochelle, NY, April 26, 2017–A growing number of preclinical studies in mice suggests that therapeutic gene delivery using recombinant adeno-associated viral vectors (rAAVs) can cause insertional mutagenesis and increase the risk of hepatocellular carcinoma. Despite the apparent safety of rAAV-mediated gene therapy in human clinical applications, the data emerging from some mouse studies emphasize the need to carefully reconsider the potential risk of genotoxicity, according to the authors of a provocative article published in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Human Gene Therapy website until May 26, 2017.

Randy Chandler and Charles Venditti, National Human Genome Research Institute, National Institutes of Health (Bethesda, MD) and Mark Sands, Washington University School of Medicine (St. Louis, MO), present a comprehensive overview of the published studies assessing rAAV gene delivery and hepatocellular carcinoma formation. In the article in Human Gene Therapy entitled “Recombinant Adeno-Associated Viral Integration and Genotoxicity: Insights from Animal Models,” the authors review the published data that suggest a potential increased risk for genotoxicity related to rAAV. They discuss the need for additional studies to characterize rAAV integration and other proposed directions for future research.

“AAV is clearly the most promising vector for Human Gene Therapy applications, yet concerns remain regarding whether or not using it incurs some risk of causing cancer,” says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Worcester, MA. “There is strong data on both sides of this issue and further research on this issue is essential.”


Research reported in this publication was supported by the Intramural Research Program of the National Human Genome Research Institute and by the National Institutes of Health under Award Number R01 NS043205. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About the Journal

Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy, British Society for Gene and Cell Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies, is an authoritative peer-reviewed journal published monthly in print and online. Led by Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Human Gene Therapy presents reports on the transfer and expression of genes in mammals, including humans. Related topics include improvements in vector development, delivery systems, and animal models, particularly in the areas of cancer, heart disease, viral disease, genetic disease, and neurological disease, as well as ethical, legal, and regulatory issues related to the gene transfer in humans. Its companion journals, Human Gene Therapy Methods, published bimonthly, focuses on the application of gene therapy to product testing and development, and Human Gene Therapy Clinical Development, published quarterly, features data relevant to the regulatory review and commercial development of cell and gene therapy products. Tables of contents for all three publications and a free sample issue may be viewed on the Human Gene Therapy website.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Nucleic Acid Therapeutics, Tissue Engineering, Stem Cells and Development, and Cellular Reprogramming. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry’s most widely read publication worldwide. A complete list of the firm’s 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

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