High-level dystrophin expression after adenovirus-mediated dystrophin minigene transfer to skeletal muscle of dystrophic dogs: prolongation of expression with immunosuppression

Human Gene Therapy
J M HowellG Karpati

Abstract

Replication-deficient adenovirus vectors (AdV) have been successfully used to transfer a truncated human dystrophin cDNA to skeletal muscle of dystrophin-deficient mdx mice. A dystrophin-deficient golden retriever dog model (GRMD) has been identified, which, unlike the mouse model, leads to a clinicopathological phenotype similar to that of Duchenne muscular dystrophy (DMD). We show for the first time that high-level dystrophin expression in skeletal muscle of GRMD dogs can be achieved by AdV-mediated gene transfer. However, a humoral and cellular immune response of the host against antigens of viral and transgene origin (similar to that occurring in mdx mice after AdV-mediated dystrophin gene transfer) leads to a decline of dystrophin expression over a 2-month period. Immunosuppression by cyclosporin significantly prolonged transgene expression. The GRMD model may help to solve the open questions pertaining to dystrophin gene transfer such as systemic delivery and improvement of muscle function before human trials for gene replacement therapy in DMD may be considered.

References

Jan 1, 1995·Advances in Genetics·R G Roberts
Nov 1, 1996·Human Molecular Genetics·Y YangJ M Wilson
Jul 1, 1997·Neuromuscular Disorders : NMD·G Karpati, H Lochmüller

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Citations

Jan 6, 2012·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Joe N KornegayEric P Hoffman
Mar 17, 2004·Toxicon : Official Journal of the International Society on Toxinology·J B Harris
Apr 9, 2001·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·S NakagawaR G Hawley
Sep 11, 2002·Neuromuscular Disorders : NMD·Dominic J Wells, Kim E Wells
Apr 30, 1999·Neuromuscular Disorders : NMD·J M Howell
Dec 15, 2000·Progress in Pediatric Cardiology·N E BowlesJ A Towbin
Nov 13, 2001·Developmental Cell·P SealeM A Rudnicki
Sep 26, 2002·Journal of Clinical Periodontology·Amanda J O'HaraJohn M C Howell
Jul 9, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Valder R ArrudaJonathan D Finn
May 19, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Valder R Arruda
Nov 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·B WangX Xiao
Feb 8, 2003·DNA and Cell Biology·Chooi May LaiP Elizabeth Rakoczy
Mar 26, 2011·Human Molecular Genetics·Aurélie GoyenvalleJeffrey Chamberlain
Mar 19, 2009·ILAR Journal·Zejing WangRainer Storb
Jan 29, 2011·Journal of Biomedicine & Biotechnology·Akinori Nakamura, Shin'ichi Takeda
Jun 29, 2010·Immunobiology·Lei WangPaula R Clemens
Jan 9, 2007·Protein Expression and Purification·Zeng-Sheng HanJian-Hong Hu
Nov 25, 2003·International Journal of Experimental Pathology·C A Collins, J E Morgan
Feb 8, 2005·Neuromuscular Disorders : NMD·Frédérique NguyenYan Cherel
Feb 25, 2015·Human Gene Therapy. Clinical Development·Dongsheng Duan
Jun 18, 2002·Journal of Cellular and Molecular Medicine·G M SmytheM D Grounds
Sep 1, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Maria J MolnarGeorge Karpati
Feb 25, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Akseli HemminkiDavid T Curiel
Feb 19, 2000·Microscopy Research and Technique·S C WatkinsL Billington
Mar 29, 2020·Frontiers in Veterinary Science·Brett D StoryHeather L Gray-Edwards
Aug 2, 2002·Clinical Orthopaedics and Related Research·W Douglas BiggarPeter N Ray
Nov 18, 2016·Journal of Neuromuscular Diseases·Merryl RodriguesToshifumi Yokota
Oct 20, 2000·The Journal of General Virology·W C Russell
Feb 9, 2019·Human Genetics·Peter P Nghiem, Joe N Kornegay

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