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 Identifying Where Genes Can Successfully Integrate

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PostSubject: Identifying Where Genes Can Successfully Integrate   Tue Aug 07, 2007 8:30 am

Source: http://www.sciencedaily.com/releases/2007/08/070802211036.htm

Science Daily Gene therapy -- whereby a retrovirus that integrates into the genome of a treated patient is used to deliver the gene of interest -- has been used to treat some individuals with inherited diseases such as X-linked SCID, a disease that causes widespread immunosuppression and therefore susceptibility to infection.
However, a small number of the treated individuals developed leukemia-like diseases because the retrovirus integrated into the genome at a site(s) that caused the cells to divide uncontrollably.

Analysis of the sites of retroviral integration in individuals treated with gene therapy is therefore of utmost importance to the further development of such gene therapy approaches and three studies that appear in the August issue of the Journal of Clinical Investigation address this issue.

The three studies -- reported by researchers from the National Center for Tumor Diseases, Heidelberg, Germany; University College London, London, United Kingdom; and the San Raffaele Telethon Institute for Gene Therapy, Milan, Italy -- indicate that the retroviruses used to deliver the genes of interest in these studies, gammaretroviruses, integrated near the 5" ends of genes that are active in the treated cell population.

Although the diversity of the detected retroviral integration sites decreased following transplantation into patients because the treated cells differentiated, the sites detected remained at the 5" end of genes active in the cell populations analyzed. Importantly, the retrovirus integration sites observed in cells from successfully treated patients were not significantly different from those observed in cells from patients that went on to develop leukemia-like disease.

As discussed in the accompanying commentary by Frederic Bushman from the University of Pennsylvania, Philadelphia, these studies are critical if researchers are to determine whether the dangers of retroviral gene therapy can be predicted and/or eliminated.

Note: This story has been adapted from a news release issued by Journal of Clinical Investigation.

Fausto Intilla's web site: www.oloscience.com
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