Findings from E. Henckaerts et al in gene therapy reported
2009 JUL 9 - (NewsRx.com) -- According to recent research from London, the United Kingdom, "A variety of viruses establish latency by integrating their genome into the host genome. The integration event generally occurs in a nonspecific manner, precluding the prediction of functional consequences from resulting disruptions of affected host genes." "The nonpathogenic adeno-associated virus (AAV) is unique in its ability to stably integrate in a site-specific manner into the human MBS85 gene. To gain a better understanding of the integration mechanism and the consequences of MBS85 disruption, we analyzed the molecular structure of AAV integrants in various latently infected human cell lines. Our study led to the observation that AAV integration causes an extensive but partial duplication of the target gene. Intriguingly, the molecular organization of the integrant leaves the possibility that a functional copy of the disrupted target gene could potentially be preserved despite the resulting rearrangements. A latently infected, Mbs85-targeted mouse ES cell line was generated to study the functional consequences of the observed duplication-based integration mechanism. AAV-modified ES cell lines continued to self-renew, maintained their multilineage differentiation potential and contributed successfully to mouse development when injected into blastocysts," wrote E. Henckaerts and colleagues. The researchers concluded: "Thus, our study reveals a viral strategy for targeted genome addition with the apparent absence of functional consequences." Henckaerts and colleagues published their study in Proceedings of the National Academy of Sciences of the United States of America (Site-specific integration of adeno-associated virus involves partial duplication of the target locus. Proceedings of the National Academy of Sciences of the United States of America, 2009;106(18):7571-7576). For additional information, contact R.M. Linden, Kings College London, School Medical, Dept. of Infectious Disease, London SE1 9RT, UK. Publisher contact information for the journal Proceedings of the National Academy of Sciences of the United States of America is: National Acad Sciences, 2101 Constitution Avenue NW, Washington, DC 20418, USA. Keywords: United Kingdom, London, Adeno-Associated Virus, Biotechnology, Embryonic Stem Cell Research, Gene Therapy, Genetics, Genomics, Viral, Virology, Virus. This article was prepared by Gene Therapy Weekly editors from staff and other reports. Copyright 2009, Gene Therapy Weekly via NewsRx.com.
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