干细胞通过旁观者效应介导的抗肌萎缩蛋白基因的外显子跳读

Title:Stem Cell-Mediated Exon Skipping of the Dystrophin Gene by the Bystander Effect

Volume: 15 Issue: 6

Author(s): Mirella Meregalli, Andrea Farini, Clementina Sitzia, Cyriaque Beley, Paola Razini, Letizia Cassinelli, Federica Colleoni, Paola Frattini, Nadia Santo, Elisabetta Galbiati, Davide Prosperi and Alessandro Tavelli, Marzia Belicchi, Luis Garcia and Yvan Torrente

Affiliation:

关键词: 旁观者效应，肌源干细胞，外显子跳读机制递送。

摘要: Duchenne muscular dystrophy (DMD) is characterized by the loss of a functional dystrophin protein; the muscles of DMD patients progressively degenerate as a result of mechanical stress during contractions, and the condition eventually leads to premature death. By means antisense oligonucleotides (AONs), it is possible to modulate pre-mRNA splicing eliminating mutated exons and restoring dystrophin open reading frame. To overcome the hurdles in using AONs for therapeutic interventions, we exerted engineered human DMD stem cells with a lentivirus, which permanently and efficiently delivered the cloned AONs. Here we describe for the first time the exosome-mediated release of AONs from engineered human DMD CD133+ stem cells allowing the rescue of murine dystrophin expression. Finally, upon release, AONs could be internalized by host cells suggesting a potential role of exosomes acting as vesicular carriers for DMD gene therapy.

Cite this article as:

Mirella Meregalli, Andrea Farini, Clementina Sitzia, Cyriaque Beley, Paola Razini , Letizia Cassinelli, Federica Colleoni, Paola Frattini, Nadia Santo, Elisabetta Galbiati, Davide Prosperi and Alessandro Tavelli, Marzia Belicchi, Luis Garcia and Yvan Torrente , Stem Cell-Mediated Exon Skipping of the Dystrophin Gene by the Bystander Effect, Current Gene Therapy 2015; 15 (6) . https://dx.doi.org/10.2174/1566523215666150929111400