By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Current study results on Apoptosis have been published. According to news originating from Philadelphia, Pennsylvania, by NewsRx correspondents, research stated, "Gene therapy provides a significant opportunity to treat a variety of inherited and acquired diseases. However, adverse immune responses toward the adeno-associated virus (AAV) antigens may limit its success."
Our news journalists obtained a quote from the research from the University of Pennsylvania, "The mechanisms responsible for immunity or tolerance toward AAV-encoded transgene products remain poorly defined. Studies in mice demonstrate that AAV2/8 gene transfer to liver is associated with immunological hyporesponsiveness toward both AAV vector and antigenic transgene product. To evaluate the role of activation-induced cell death (AICD) and cytokine withdrawal (intrinsic cell death) in the deletion of mature T lymphocytes, we compared immunological responses in hepatic AAV2/8 transfer in murine recipients lacking the Fas receptor, and recipients overexpressing Bcl-xL, to WT murine counterparts. Prolonged transgene expression was dependent on both Fas signaling and Bcl-xL regulated apoptosis in T cells. Abrogation of intrinsic cell death enhanced Th1 responses, whereas AICD functioned to limit neutralizing antibody production toward AAV2/8. In addition, immune hyporesponsiveness and stable transgene expression was dependent on upregulation of FasL expression on transduced hepatocytes and a corresponding apoptosis of infiltrating Fas (+) cells."
According to the news editors, the research concluded: "These data provide evidence that both AICD and apoptosis due to cytokine withdrawal of lymphocytes are essential for immune hyporesponsiveness toward hepatic AAV2/8-encoded transgene product in the setting of liver gene transfer."
For more information on this research see: The Role of Apoptosis in Immune Hyporesponsiveness Following AAV8 Liver Gene Transfer. Molecular Therapy, 2013;21(12):2227-2235. Molecular Therapy can be contacted at: Nature Publishing Group, 75 Varick St, 9TH Flr, New York, NY 10013-1917, USA. (Elsevier - www.elsevier.com; Molecular Therapy - www.elsevier.com/wps/product/cws_home/622922)
The news correspondents report that additional information may be obtained from S.M. Faust, University of Pennsylvania, Dept. of Pathol & Lab Med, Gene Therapy Program, Philadelphia, PA 19104, United States. Additional authors for this research include P. Bell, Y.Q. Zhu, J. Sanmiguel and J.M. Wilson (see also Apoptosis).
Keywords for this news article include: Biotechnology, Apoptosis, Immunology, Blood Cells, Lymphocytes, Philadelphia, Pennsylvania, Gene Therapy, United States, Bioengineering, Mononuclear Leukocytes, Hemic and Immune Systems, North and Central America
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