PMID: 9557710Apr 29, 1998Paper

Transduction of dendritic cells by DNA viral vectors directs the immune response to transgene products in muscle fibers

Journal of Virology
K JoossJ M Wilson

Abstract

Immune responses to vector-corrected cells have limited the application of gene therapy for treatment of chronic disorders such as inherited deficiency states. We have found that recombinant adeno-associated virus (AAV) efficiently transduces muscle fibers in vivo without activation of cellular and humoral immunity to neoantigenic transgene products such as beta-galactosidase, which differs from the experience with recombinant adenovirus, where vibrant T-cell responses to the transgene product destroy the targeted muscle fibers. T cells activated following intramuscular administration of adenovirus expressing lacZ (AdlacZ) can destroy AAVlacZ-transduced muscle fibers, indicating a prior state of immunologic nonresponsiveness in the context of AAV gene therapy. Adoptive transfer of dendritic cells infected with AdlacZ leads to immune mediated elimination of AAVlacZ-transduced muscle fibers. AAVlacZ-transduced antigen-presenting cells fail to demonstrate beta-galactosidase activity and are unable to elicit transgene immunity in adoptive transfer experiments. These studies indicate that vector-mediated transduction of dendritic cells is necessary for cellular immune responses to muscle gene therapy, a step which AAV avoids, provid...Continue Reading

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Citations

Sep 22, 1999·Gene Therapy·N ChirmuleJ Wilson
Jul 21, 1999·Proceedings of the National Academy of Sciences of the United States of America·V M RiveraM Gilman
Aug 3, 1999·Biological Chemistry·H Büeler
Apr 25, 2000·Human Gene Therapy·R SarkarH H Kazazian
Apr 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S A PrasadJ W Yewdell
Jul 23, 2002·Journal of Virology·Mihail Y MastakovMatthew J During
Aug 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·Guang-Ping GaoJames M Wilson
Oct 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Hiroshi TakahashiTakashi Shimada
Feb 8, 2003·DNA and Cell Biology·Chooi May LaiP Elizabeth Rakoczy
Jul 2, 2003·The Journal of Pharmacy and Pharmacology·Katrina A BicknellGavin Brooks
Aug 9, 2003·Expert Opinion on Drug Safety·Paul E MonahanMark S Sands
Dec 19, 2003·Expert Opinion on Biological Therapy·Selvarangan Ponnazhagan
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nicola J PhilpottErik Falck-Pedersen
Jul 14, 2004·Medicinal Research Reviews·Hai-sheng ZhouChih-chuan Liang
Mar 12, 2005·Human Gene Therapy·Julie L BoyerRonald G Crystal
Jun 5, 2007·Expert Review of Vaccines·Teng Chih YangJonathan L Bramson
Jun 28, 2007·Human Gene Therapy·Brad E HoffmanRoland W Herzog
Apr 11, 2008·Gene Therapy·I E AlexanderJ Christodoulou
May 7, 2009·Antioxidants & Redox Signaling·Ebo D de Muinck
Mar 1, 2008·Future Cardiology·Oliver J MüllerHugo A Katus
Nov 26, 2009·Animal Biotechnology·Tomislav Modric, Ayalew Mergia

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