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Gene modification strategies using AO-mediated exon skipping and CRISPR/Cas9 as potential therapies for Duchenne muscular dystrophy patients

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journal contribution
posted on 11.12.2020, 10:19 by Marthe Helen Solzberg, Maryam Shariatzadeh, Sammy WilsonSammy Wilson
Duchenne muscular dystrophy (DMD) is an X-linked genetic disease affecting 1 in 5,000 young males worldwide annually. Patients experience muscle weakness and loss of ambulation at an early age, with ~75% reduced life expectancy. Recently developed genetic editing strategies aim to convert severe DMD phenotypes to a milder disease course. Amongst these, Antisense oligonucleotide (AO)-mediated exon skipping and Adeno-associated viral-delivered clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9 (AAV-delivered CRISPR/Cas9) gene editing have shown promising results in restoring dystrophin protein expression and functionality in skeletal and heart muscle in both animals and human cells in vivo and in vitro. However, the therapeutic benefits currently remain unclear. The aim of this review is to compare the potential therapeutic benefits, efficacy, safety, and clinical progress of AO-mediated exon skipping and CRISPR/Cas9 gene editing strategies. Both techniques have demonstrated therapeutic benefit and long-term efficacy in clinical trials. AAV-delivery of CRISPR/Cas9 may potentially correct disease-causing mutations following a single treatment compared to the required continuous AO/PMO-delivery of exon skipping drugs. The latter has potential to increase dystrophin expression in skeletal/heart muscle with sustained effects. However, therapeutic challenges including the need for optimised delivery must be overcome in to advance current clinical data.

History

School

  • Mechanical, Electrical and Manufacturing Engineering
  • Sport, Exercise and Health Sciences

Published in

Engineering Biology

Volume

4

Issue

3

Pages

37-42

Publisher

Institute of Engineering and Technology

Version

VoR (Version of Record)

Publisher statement

This is an Open Access Article. It is published by IET under the Creative Commons Attribution 3.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/3.0/

Acceptance date

30/11/2020

Publication date

2020-12-01

ISSN

2398-6182

eISSN

2398-6182

Language

en

Depositor

Dr Sammy Wilson Deposit date: 10 December 2020