CRISPR-Cas9 System for Intervening Duchenne Muscular Dystrophy in Mice Models: A Meta-Analysis

Objective This meta-analysis aims to summarize the current literature on CRISPR-Cas9 system as a potential therapeutic tool against Duchenne muscular dystrophy. Background Duchenne muscular dystrophy (DMD) is a fatal monogenic disorder with limited treatment options that affect 1 in 5,000 boys. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) system has been increasingly studied as a potential gene editing intervention against DMD with accumulating supportive evidence in in-vitro, ex-vivo, and in-vivo experiments. Method A meta-analysis of peer reviewed, experimental in-vivo studies on CRISPR-Cas9 system as a gene therapy against DMD were conducted. PubMed and EMBASE databases were utilized for the electronic search of the current literature on August 2020. The primary outcomes were (1) restoration of dystrophin expression measured by Western blots and (2) immunohistochemistry as well as (3) change in specific force of skeletal muscles in mice models of DMD after the intervention. The meta-analysis utilized random-intercept logistic regression model, maximum-likelihood estimator for tau2, logit transformation, and normal approximation confidence interval for individual studies. Results Seventeen and eleven studies were identified for the qualitative and quantitative meta-analyses, respectively. Both systemic and intramuscular administrations of CRISPR-Cas9 system partially restored dystrophin expression and skeletal muscle function with little heterogeneity between available studies. Conclusion Current literature supports that CRISPR-Cas9 system is a viable intervention against DMD, substantiated by the post-intervention improvements in dystrophin expression and skeletal muscle strengths. Further studies on refining CRISPR-Cas9 delivery system and studies with higher sample size are warranted.