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Alternate Translational Initiation of Dystrophin: A Novel Therapeutic Approach

  • Nicolas Wein
  • Kevin M. FlaniganEmail author
Chapter

Abstract

A founder allele in the DMD gene results in a syndrome ranging from minimally symptomatic Becker muscular dystrophy to asymptomatic hyperCKemia via expression of a highly functional N-terminal deleted version of the dystrophin protein (the ΔCH1 isoform). Translation of this protein results from utilization of a recently discovered internal ribosome entry site (IRES) within exon 5. The IRES is not active in the presence of a duplication of exon 2—the most common single-exon duplication—but is active in its absence. We have developed an AAV-encapsidated U7snRNA vector that targets and induces skipping of exon 2, resulting in either expression of a wild-type dystrophin or of the ΔCH1 isoform, either of which is therapeutic.

Keywords

Duchenne muscular dystrophy Actin-binding domain Exon skipping Internal ribosome entry site 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.The Center for Gene TherapyNationwide Children’s HospitalColumbusUSA
  2. 2.Department of PediatricsThe Ohio State UniversityColumbusUSA
  3. 3.Department of NeurologyThe Ohio State UniversityColumbusUSA

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