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Full-length dysferlin transfer by the hyperactive Sleeping Beauty transposase restores dysferlin-deficient muscle

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Item Type:Article
Title:Full-length dysferlin transfer by the hyperactive Sleeping Beauty transposase restores dysferlin-deficient muscle
Creators Name:Escobar, H. and Schöwel, V. and Spuler, S. and Marg, A. and Izsvák, Z.
Abstract:Dysferlin-deficient muscular dystrophy is a progressive disease characterized by muscle weakness and wasting for which there is no treatment. It is caused by mutations in DYSF, a large, multiexonic gene that forms a coding sequence of 6.2 kb. Sleeping Beauty (SB) transposon is a nonviral gene transfer vector, already used in clinical trials. The hyperactive SB system consists of a transposon DNA sequence and a transposase protein, SB100X, that can integrate DNA over 10 kb into the target genome. We constructed an SB transposon-based vector to deliver full-length human DYSF cDNA into dysferlin-deficient H2K A/J myoblasts. We demonstrate proper dysferlin expression as well as highly efficient engraftment (>1,100 donor-derived fibers) of the engineered myoblasts in the skeletal muscle of dysferlin- and immunodeficient B6.Cg-Dysf(prmd) Prkdc(scid)/J (Scid/BLA/J) mice. Nonviral gene delivery of full-length human dysferlin into muscle cells, along with a successful and efficient transplantation into skeletal muscle are important advances towards successful gene therapy of dysferlin-deficient muscular dystrophy.
Keywords:Dysferlin, Gene Therapy, Myoblast Transplantation, Sleeping Beauty Transposon, Animals, Mice
Source:Molecular Therapy - Nucleic Acids
ISSN:2162-2531
Publisher:Nature Publishing Group (U.S.A.)
Volume:5
Page Range:e277
Date:19 January 2016
Official Publication:https://doi.org/10.1038/mtna.2015.52
PubMed:View item in PubMed

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