• High levels of dystrophin cDNA expression, and an efficient distant transfection effect with preferential intranuclei inclusion of MF-2 vehicle, are very encouraging for the development of a new constructive strategy in gene therapy trials of DMD. (nature.com)
  • Both utrophin and dystrophin share a similar domain architecture with N-terminal actin-binding domains and C-terminal variable domains separated by 22 or 24 spectrin-like repeats respectively. (massey.ac.nz)
  • In this thesis, high-resolution structures of the N-terminal first spectrin repeat domains from utrophin and dystrophin have been determined by x-ray crystallography to 1.95 and 2.3 Å. (massey.ac.nz)
  • Despite multiple structures of spectrin repeats in the Protein Data Bank from a-actinin, spectrin and plectin these are the first structures determined for any of the spectrin repeats from utrophin and dystrophin. (massey.ac.nz)
  • The repeat domain structure reveals the relationship between the canonical spectrin repeat domain sequence motif and the structural domain for utrophin and dystrophin, showing the N-terminal first spectrin repeat to be extended at the C-terminal end. (massey.ac.nz)
  • Studies using steered molecular dynamics suggested that the force required for unfolding the N-terminal first spectrin repeat domain from utrophin is higher in comparison to that of the N-terminal first spectrin repeat from dystrophin. (massey.ac.nz)
  • MF-2/dystrophin cDNA par- ticles were detected by FISH analysis in about 60-70% of myofiber nuclei in muscles of injected and contralateral limbs 7 days after application. (nature.com)
  • The presence of human dystrophin cDNA and its products in all skeletal muscles and in different internal organs was proven by PCR and RT-PCR analysis. (nature.com)
  • The absence of any efficient pharmaceutical or biological (myoblast transplantation) methods for the treatment of DMD makes the development of gene therapy approaches for widespread systemic delivery of dystrophin gene to skeletal muscles very urgent for the correction and management of this primary lethal genetic disorder. (nature.com)
  • 1, 2 Myofibers lacking dystrophin are abnormally susceptible to contraction-induced sarcolemma damage with subsequent myofiber dysfunction, necrosis and regeneration leading ultimately to the replacement of the lost fibers by adipose and connective tissue and premature death often associated with cardiomyopathy. (nature.com)
  • Dystrophin is a large cytoskeletal protein belonging to the spectrin superfamily, that links intracellular F-actin to the extracellular matrix via a membrane-associated glyco-protein complex thus maintaining structural rigidity and flexibility. (massey.ac.nz)
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