Editorial: Genome and transcriptome editing to understand and treat neuromuscular diseases.

Abstract

Neuromuscular diseases such as Duchenne muscular dystrophy and facioscapulohumeral muscular dystrophy are debilitating conditions that affect millions of individuals worldwide. In recent years, there has been a growing interest in the use of genome and transcriptome editing techniques to understand and treat these diseases. This Research Topic brings together four articles that highlight the latest advances in this field. The first article “A Single Transcript Knockdown-Replacement Strategy Employing 5′ UTR Secondary Structures to Precisely Titrate Rescue Protein Translation” by Millette et al., presents a new strategy for precisely titrating rescue protein translation in cases of diseases caused by coding mutations such as amyotrophic lateral sclerosis (ALS). The authors developed amodular, single-transgene expression system that allows control over translation from high-expression, ubiquitous promoters. This system uses “attenuator” sequences in the 5’UTRwhich predictably diminish the translation of the paired gene, providing wide general utility. The authors also demonstrate that this approach can be used to achieve a knockdown and rescue effect by pairing microRNA-adapted shRNAs alongside their respective replacement gene on a single transcript. They also showed that this approach can be used to replace the SOD1 gene in stable cell lines and demonstrate complete and predictable control over replacement of SOD1 by varying the strength of attenuators. This study highlights the potential utility of this approach in treating monogenic diseases caused by heterogeneous mutations. The second article “Development of Therapeutic RNA Manipulation for Muscular Dystrophy” by Saifullah et al., reviews the current state of therapeutic RNA manipulation for muscular dystrophies, specifically Duchenne muscular dystrophy (DMD). DMD is a severe monogenic disease caused by mutations in the DMD gene, leading to muscle degeneration and atrophy early in life and premature death. This article highlights the potential of oligonucleotide-based therapeutics, specifically exon skipping using antisense oligonucleotides (ASO), as a promising strategy for treating OPEN ACCESS