Universal gene editing strategies to treat Duchenne Muscular Dystrophy.

Responsable du Stage : Mario Amendola, Maëlle Ralu

E-mail:  mamendola@genethon.fr, mralu@genethon.fr


Résumé du Projet de Stage 

Duchenne muscular dystrophy (DMD) is a fatal X-linked neuromuscular disorder affecting 1 in 5 000 newborn males. It is caused by loss of function mutations in the dystrophin gene. DMD patients are restricted to wheelchair by the age of 12 and usually succumb to cardiac or respiratory complications in their late twenties. Despite recent progress and extensive research over the last three decades, there is still no effective treatment for DMD. Gene Therapy (GT) trials using AAV to express functional truncated micro-dystrophin genes in muscles are currently on-going and therapeutic benefits still need to be assessed. A promising alternative is based on upregulating surrogate genes able to compensate for the lack of dystrophin in DMD. This therapeutic strategy is mutation-independent and has the advantage of being suitable for all patient. Our lab has used the CRISPR-Cas9 technology on several target sites and promising results were obtained. The student will further characterize these targets and test the potential of combined treatments.


Main tasks

Cell culture

Molecular biology techniques (DNA and RNA extraction, PCR, Western Blot, etc.)

CRISPR techniques (gRNA design and testing, application)

References et publications récentes de l’équipe

Sengupta K, Loro E, Khurana TS. PMO-based let-7c site blocking oligonucleotide (SBO) mediated utrophin upregulation in mdx mice, a therapeutic approach for Duchenne muscular dystrophy (DMD). Sci Rep. 2020 Dec 9;10(1):21492. doi: 10.1038/s41598-020-76338-1. PMID: 33298994; PMCID: PMC7726560.

Kennedy TL, Guiraud S, Edwards B, Squire S, Moir L, Babbs A, Odom G, Golebiowski D, Schneider J, Chamberlain JS, Davies KE. Micro-utrophin Improves Cardiac and Skeletal Muscle Function of Severely Affected D2/mdx Mice. Mol Ther Methods Clin Dev. 2018 Oct 16;11:92-105. doi: 10.1016/j.omtm.2018.10.005. PMID: 30417024; PMCID: PMC6216100.

Sengupta K, Mishra MK, Loro E, Spencer MJ, Pyle AD, Khurana TS. Genome Editing-Mediated Utrophin Upregulation in Duchenne Muscular Dystrophy Stem Cells. Mol Ther Nucleic Acids. 2020 Aug 29;22:500-509. doi: 10.1016/j.omtn.2020.08.031. PMID: 33230452; PMCID: PMC7554652.

Ce projet s’inscrit-il dans la perspective d’une thèse :

          non X


Intitulé de l’Unité : INTEGRARE UMR951

Nom du Responsable de l’Unité : Anne Galy

Nom du Responsable de l’Équipe : Mario Amendola

Adresse :  1 bis rue de l’Internationale, Evry