AAV and Insertional Mutagenesis
Authors: David A Williams
Journal: Molecular Therapy (2007)

In this issue of Molecular Therapy, David Russell provides an invited commentary on data presented at the tenth annual meeting of the American Society of Gene Therapy that strongly suggested that adenovirus-associated virus (AAV) vector insertion could in certain models be linked to the development of cancer.1Russell DW AAV vectors, insertional mutagenesis, and cancer.Mol. Ther. 2007; 15: 1740-1743Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar A short report describing the data that are the subject of this commentary has recently been published in Science.2Donsante A Miller DG Li Y Vogler C Brunt EM Russell DW et al.AAV vector integration sites in mouse hepatocellular carcinoma.Science. 2007; 317: 477Crossref PubMed Scopus (483) Google Scholar The study shows that newborn mouse pups injected with an AAV vector expressing β-glucuronidase and containing the cytomegalovirus enhancer develop hepatic tumors. Although complete molecular analysis has been hindered by difficulties inherent in AAV vectorology, Russell and colleagues provide a compelling argument that the tumors arose as a result of AAV insertions and most likely because of insertional mutagenesis by this vector. As Russell points out in the commentary, AAV vectors have previously been linked to the development of tumors in animal models, and even in this case the observation is limited to a specific animal model and the use of newborn pups. Nonetheless, the potential implications for the use of AAV vector in human trials are noteworthy in the sense that an oft-stated theoretical advantage of this vector system has been the lack of the potential for insertional side effects. The story makes for good reading and points to the continuing maturation of the field of gene therapy with respect to evaluation of clinical application of gene transfer vectors and the appropriate ongoing scrutiny of risks and benefits of gene therapy approaches. The editors of Molecular Therapy believe that such short commentaries provide the readership of the journal with important and timely information regarding aspects of the field often not commented on in other forums. By all indications, this approach is appreciated. In the past 6 months, we have noted a significant increase in submissions to the journal and we have recently learned that the 2006 impact factor has increased to over 5.8 (from 5.4 in 2005), with an impressive increase in the immediacy index to 1.325. Molecular Therapy is now ranked fourth among 76 journals in immediacy index in the category of Research and Experimental Medicine and fifth among 140 journals in Biotechnology and Applied Microbiology. These numbers primarily reflect citations to articles published in 2004–2006, so we anticipate even higher numbers next year as the full impact of our recent redesign and move to Nature Publishing Group (NPG) is felt. Rob Frederickson and I are very proud of these positive developments for the journal and continue to work hard to maintain a fast and fair review process. We have maintained an average time to first decision of 22 days during the journal transition to NPG. We look forward to working with you to continue—and increase—the quality and impact of the articles we publish in the future. Potential contributors are encouraged to contact us at [email protected] for rapid consideration of potential commentaries, review articles, and primary research contributions.