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OFFRE DE STAGE – Master 1 Recherche : Impact of dystrophin restoration on neurological disorders in a mouse model

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Coordonnées du laboratoire d’accueil :

Laboratoire biothérapies des maladies neuromusculaires, dirigé par Aurélie Goyenvalle, PhD, DR Inserm


UFR des sciences de la santé

2 Avenue de la source de la Bièvre

78180 Montigny le Bretonneux

Nom et coordonnées de l’encadrant :

Ophélie Vacca, PhD

Mail :

Summary of the research project

Keywords: Antisense oligonucleotides, gene therapy, splicing modulation, neuromuscular disorders, AAV vectors

Our laboratory focuses on novel antisense strategies based on mRNA modulation for the treatment of neuromuscular and neurodegenerative diseases. We have in particular pioneered the exon-skipping approach mediated by AAV vectors as a therapy for Duchenne muscular dystrophy (DMD).  Antisense strategies mediated by antisense oligonucleotides (AON) or viral vectors such as AAVs hold great promise for therapeutic correction in many genetic diseases. However, despite advances in AON chemistry and design, as well as AAV vectors, these therapies have not yet reached their full therapeutic potential, notably because of poor tissue uptake.

The proposed project aims at assessing the impact of dystrophin postnatal restoration on neurobehavioral deficits known in dystrophic mdx52 mouse model using exon-skipping technology by naked AONs (modified in tricycloDNA) or vectorized (AAV-U7 system), or direct gene replacement by AAVs (for Dp140 or Dp71).

In this project, the student will use a variety of techniques to evaluate the efficacy of various combined strategies involving RNA and protein extractions, RT-PCR and qPCR analysis, Western Blot, histology, immunohistochemistry, microscopy, etc.

Latest publications from the laboratory related to the project

  1. Zarrouki F, Relizani K, Bizot F, Tensorer T, Garcia L, Vaillend C and Goyenvalle A. Partial restoration of brain dystrophin and behavioral deficits by exon-skipping in the muscular dystrophy X-linked (mdx) mouse. Annals of Neurology. 2022 May 19. doi: 10.1002/ana.26409
  2. Relizani K, Echevarría L, Zarrouki F, Gastaldi C, Dambrune C, Aupy P, Haeberli A, Komisarski M, Tensorer T, Larcher T, Svinartchouk F, Vaillend C, Garcia L and Goyenvalle A. Palmitic acid conjugation enhances potency of tricyclo-DNA splice switching oligonucleotides. Nucleic Acids Res. 2022 jan 11;50(1):17-34. doi: 10.1093/nar/gkab1199.
  3. Saoudi A, Zarrouki F, Sebrie C, Izabelle C, Goyenvalle A, Vaillend C. Emotional behaviour and brain anatomy of the mdx52 mouse model of Duchenne muscular dystrophy. Dis Model Mech. 2021 Sep 1;14(9):dmm049028. doi: 10.1242/dmm.049028
  4. Saoudi A and Goyenvalle A. RNA splicing modulation: Therapeutic progress and perspectives.  Med Sci (Paris) 2021 Jun-Jul;37(6-7):625-631. doi: 10.1051/medsci/2021091
  5. Ferlini A, Goyenvalle A. and Muntoni F. RNA-targeted drugs for neuromuscular diseases. Science 2021 Jan 1;371(6524):29-31.