A canine minidystrophin is functional and therapeutic in mdx mice

Gene Therapy
Bing WangXiao Xiao

Abstract

Duchenne muscular dystrophy (DMD) is the most common and lethal genetic muscle disorder lacking a curative treatment. We wish to use the dystrophin-deficient golden retriever muscular dystrophy (GRMD) dog, a canine model of DMD, to investigate adeno-associated virus (AAV) vector-mediated minidystrophin gene therapy. The dog model is useful in evaluating vector dose requirement and immunological consequences owing to its large size and outbred nature. In this study, we have cloned and constructed a canine minidystrophin gene vector. Owing to limited availability of the GRMD dogs, here we first examined the functions and therapeutic effects of the canine minidystrophin in the mdx mouse model. We observed efficient minigene expression without cellular immune responses in mdx mice after AAV1-cMinidys vector intramuscular injection. We also observed restoration of the missing dystrophin-associated protein complex (DPC) onto the sarcolemma, including sarcoglycans and dystrobrevin, and a partial restoration of alpha-syntrophin and neural nitric oxide synthase (nNOS). In addition, minidystrophin treatment ameliorated dystrophic pathology, such as fibrosis and myofiber central nucleation (CN). CN remained minimal (<2%) after AAV injecti...Continue Reading

References

Jun 15, 1989·The New England Journal of Medicine·J R MendellJ Florence
May 23, 1998·Human Molecular Genetics·R H CrosbieK P Campbell
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·G D ThomasR G Victor
Apr 10, 1999·Journal of Virology·W XiaoJ M Wilson
Nov 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·B WangX Xiao
Oct 3, 2001·The Journal of Cell Biology·M WehlingJ G Tidball
Mar 5, 2002·Nature Medicine·Scott Q HarperJeffrey S Chamberlain
Jun 22, 2002·Current Opinion in Genetics & Development·Madeleine Durbeej, Kevin P Campbell
Oct 29, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Madoka YoshimuraShin'ichi Takeda
Apr 12, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Zejing WangRainer Storb

❮ Previous
Next ❯

Citations

Jan 28, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cathryn S MahBarry J Byrne
Feb 25, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christophe PichavantJacques P Tremblay
Jun 3, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Joe N KornegayXiao Xiao
Jul 21, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Zheng FanWilliam Powers
Nov 10, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Dawn E BowlesR Jude Samulski
Apr 7, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christophe PichavantJacques P Tremblay
Jun 18, 2010·Human Gene Therapy·Christophe PichavantJacques P Tremblay
Feb 6, 2010·Expert Opinion on Biological Therapy·Ying TangBing Wang
Mar 17, 2009·Journal of Neuropathology and Experimental Neurology·Marina FaninCorrado Angelini
Mar 5, 2016·American Journal of Human Genetics·Kay E Davies
Nov 1, 2008·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Bing WangXiao Xiao
Oct 13, 2011·The Journal of Pathology·Virginie Carmignac, Madeleine Durbeej
Apr 16, 2010·Gene Therapy·P ChapdelaineJ P Tremblay
Oct 3, 2018·Biological & Pharmaceutical Bulletin·HyeongSeob KwakSang-Han Lee
Jan 1, 2011·Current Protocols in Mouse Biology·Christine I WooddellGuofeng Zhang
Jun 19, 2013·Cellular and Molecular Life Sciences : CMLS·Alessandra GovoniGiacomo P Comi
May 14, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiangyu ChuBing Wang
Mar 6, 2009·Cellular Signalling·Ira Verena RöderRüdiger Rudolf

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.