Background
Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder caused by mutations in the dystrophin gene, leading to a complete absence of the dystrophin protein. Advances in gene therapy have focused on restoring dystrophin expression, with nonviral gene delivery systems emerging as a promising alternative to viral vectors due to their reduced immunogenicity and improved safety profile.
Objectives
This comprehensive meta-analysis aims to assess the efficacy of nonviral gene delivery systems in DMD, focusing on their impact on dystrophin expression, functional outcomes, and safety.
Methods
A systematic search was conducted using PubMed, Embase, Cochrane Library, and ClinicalTrials.gov to identify randomized controlled trials (RCTs), non-randomized trials, and preclinical studies assessing nonviral delivery systems for DMD. Data were extracted and analyzed using R and Python, following PRISMA guidelines. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool for RCTs and SYRCLE’s Risk of Bias tool for animal studies.
Results
The meta-analysis included 20 studies with a total of 1,325 participants and animal models. Nonviral gene delivery systems, including liposomes, nanoparticles, and polymer-based carriers, significantly increased dystrophin expression levels in muscle tissue (mean increase: 18.7%, 95% CI: 12.4–24.9%, p < 0.001) compared to control groups. Functional outcomes, assessed via grip strength and locomotion tests, showed significant improvements (mean increase: 2.6 points on functional scales, 95% CI: 1.8–3.4, p < 0.001). Safety analysis revealed that nonviral systems exhibited a lower incidence of immune-related adverse events (RR: 0.42, 95% CI: 0.29–0.59, p < 0.001) compared to viral vectors. Notably, polymer-based carriers demonstrated the highest efficacy in enhancing dystrophin expression, while lipid-based systems had the best safety profile.
Conclusion
This meta-analysis provides robust evidence supporting the potential of nonviral gene delivery systems to achieve clinically meaningful dystrophin restoration, functional improvement, and enhanced safety in DMD therapy. Further research is recommended to refine delivery methods, optimize dosing strategies, and evaluate long-term outcomes to facilitate clinical translation. Nonviral delivery systems offer a viable path toward safer and more effective gene therapy for DMD.