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Scientists at Kyushu University, Department of Pathology publish new data on gene therapy
April 14th, 2008
2008 APR 14 -- Fresh data on gene therapy are presented in the report 'Newly-developed Sendai virus vector for retinal gene transfer: reduction of innate immune response via deletion of all envelope-related genes.' "Recombinant Sendai virus vectors (rSeV) constitute a new class of cytoplasmic RNA vectors that have shown efficient gene transfer in various organs, including retinal tissue; however, the related immune responses remain to be overcome in view of clinical applications. We recently developed a novel rSeV from which all envelope-related genes were deleted (rSeV/dFdMdHN) and, in the present study, assess host immune responses following retinal gene transfer," scientists writing in the Journal of Gene Medicine - Gene Therapy Clinical Trial Database report. "rSeV/dFdMdHN or conventional F-gene deleted rSeV (rSeV/dF) was injected into subretinal space of adult Wistar rats or C57BL/6 mice. The transgene expression and histopathological findings were assessed at various time points. Immunological assessments, including the expression of proinflammatory cytokines, natural killer (NK)-cell activity, as well as SeV-specific cytotoxic T lymphocytes (CTLs) and antibodies, were performed following vector injection. rSeV/dFdMdHN showed high gene transfer efficiency into the retinal pigment epithelium at an equivalent level to that seen with rSeV/dF. In the early phase, the upregulation of proinflammatory cytokines, local inflammatory cell infiltration and tissue damage that were all prominently seen in rSeV/dF injection were dramatically diminished using rSeV/dFdMdHN. NK cell activity was also decreased, indicating a reduction of the innate immune response. In the later phase, on the other hand, CTL activity and anti-SeV antibodies were similarly induced, even using rSeV/dFdMdHN, and resulted in transient transgene expression in both vector types," wrote Y. Murakami and colleagues, Kyushu University, Department of Pathology. The researchers concluded: "Deletion of envelope-related genes of rSeV dramatically reduces the vector-induced retinal damage and may extend the utility for ocular gene transfer; however, further studies regulating the acquired immune response are required to achieve long-term transgene expression of rSeV." Murakami and colleagues published their study in the Journal of Gene Medicine - Gene Therapy Clinical Trial Database (Newly-developed Sendai virus vector for retinal gene transfer: reduction of innate immune response via deletion of all envelope-related genes. Journal of Gene Medicine - Gene Therapy Clinical Trial Database, 2008;10(2):165-76). Additional information can be obtained by contacting Y. Murakami, Graduate School of Medical Sciences, Dept. of Pathology, Kyushu University, Fukuoka, Japan. The publisher of the Journal of Gene Medicine - Gene Therapy Clinical Trial Database can be contacted at: John Wiley & Sons Ltd., the Atrium, Southern Gate, Chichester PO19 8SQ, W Sussex, England. Keywords: Japan, Fukuoka, Biotechnology, Clinical Trial Research, Cytokines, Drug Development, Gene Therapy, Genetics, Genomics, Pathology, Pharmaceuticals, Sendai Virus, Treatment, Virology. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2008, Biotech Business Week via NewsRx.com.
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