Gene Editing to Tackle Facioscapulohumeral Muscular Dystrophy

Virginie Mariot; Julie Dumonceaux

doi:10.3389/fgeed.2022.937879

Gene Editing to Tackle Facioscapulohumeral Muscular Dystrophy

Front Genome Ed. 2022 Jul 15:4:937879. doi: 10.3389/fgeed.2022.937879. eCollection 2022.

Authors

Virginie Mariot¹, Julie Dumonceaux¹

Affiliation

¹ NIHR Biomedical Research Centre, Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Trust, University College London, London, United Kingdom.

Abstract

Facioscapulohumeral dystrophy (FSHD) is a skeletal muscle disease caused by the aberrant expression of the DUX4 gene in the muscle tissue. To date, different therapeutic approaches have been proposed, targeting DUX4 at the DNA, RNA or protein levels. The recent development of the clustered regularly interspaced short-palindromic repeat (CRISPR) based technology opened new avenues of research, and FSHD is no exception. For the first time, a cure for genetic muscular diseases can be considered. Here, we describe CRISPR-based strategies that are currently being investigated for FSHD. The different approaches include the epigenome editing targeting the DUX4 gene and its promoter, gene editing targeting the polyadenylation of DUX4 using TALEN, CRISPR/cas9 or adenine base editing and the CRISPR-Cas9 genome editing for SMCHD1. We also discuss challenges facing the development of these gene editing based therapeutics.

Keywords: CRISPR; DUX4; FSHD; TALEN; cas9; gene editing; muscle; therapy.

Publication types

Review