Restoration of Human Dystrophin Following Transplantation of Exon-Skipping-Engineered DMD Patient Stem Cells into Dystrophic Mice

Rachid Benchaouir, Mirella Meregalli, Andrea Farini, Giuseppe D'Antona, Marzia Belicchi, Aurélie Goyenvalle, Maurizio Battistelli, Nereo Bresolin, Roberto Bottinelli, Luis Garcia, Yvan Torrente

Research output: Contribution to journalArticlepeer-review

Abstract

Duchenne muscular dystrophy (DMD) is a hereditary disease caused by mutations that disrupt the dystrophin mRNA reading frame. In some cases, forced exclusion (skipping) of a single exon can restore the reading frame, giving rise to a shorter, but still functional, protein. In this study, we constructed lentiviral vectors expressing antisense oligonucleotides in order to induce an efficient exon skipping and to correct the initial frameshift caused by the DMD deletion of CD133+ stem cells. The intramuscular and intra-arterial delivery of genetically corrected CD133 expressing myogenic progenitors isolated from the blood and muscle of DMD patients results in a significant recovery of muscle morphology, function, and dystrophin expression in scid/mdx mice. These data demonstrate that autologous engrafting of blood or muscle-derived CD133+ cells, previously genetically modified to reexpress a functional dystrophin, represents a promising approach for DMD.

Original languageEnglish
Pages (from-to)646-657
Number of pages12
JournalCell Stem Cell
Volume1
Issue number6
DOIs
Publication statusPublished - Dec 13 2007

Keywords

  • HUMDISEASE
  • STEMCELL

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

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