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Efficient and Fast Functional Screening of Microdystrophin Constructs In Vivo and In Vitro for Therapy of Duchenne Muscular Dystrophy

Lookup NU author(s): Dr Louise Jorgensen, Dr Steven Laval, Professor Hanns Lochmuller

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Abstract

Duchenne muscular dystrophy (DMD) is an X-linked, lethal genetic disorder affecting the skeletal muscle compartment, and is caused by mutation(s) in the dystrophin gene. Gene delivery of microdystrophin constructs using adeno-associated virus (AAV) and antisense-mediated exon skipping restoring the genetic reading frame are two of the most promising therapeutic strategies for DMD. Both approaches use microdystrophin proteins either directly as a desired construct for gene delivery, using the capacity-limited AAV vectors, or as the therapeutic outcome of gene splicing. Although functionality of the resulting artificial dystrophin proteins can be predicted in silico, experimental evidence usually obtained in transgenic mice is required before human trials. However, the enormous number of potential constructs makes screening assays for dystrophin protein function in vitro and in vivo highly desirable. Here we present data showing that functionality of microdystrophins can be assessed using relatively simple and fast techniques.

Publication metadata

Author(s): Jorgensen LH, Larochelle N, Orlopp K, Dunant P, Dudley RWR, Stucka R, Thirion C, Walter MC, Laval SH, Lochmuller H

Publication type: Article

Publication status: Published

Journal: Human Gene and Cell Therapy

Year: 2009

Volume: 20

Issue: 6

Pages: 641-650

ISSN (print): 1946-6536

ISSN (electronic): 1946-6544

Publisher: Mary Ann Liebert, Inc. Publishers

URL: http://dx.doi.org/10.1089/hum.2008.162

DOI: 10.1089/hum.2008.162

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