Neurosurgery Resident and Clinical Researcher MME Foundation Mansoura, Egypt
Disclosure(s):
Mahmoud M. Elsayed, MD: No financial relationships to disclose
Introduction: Adeno-associated virus (AAV)-mediated gene therapies have emerged as a promising approach for treating genetic disorders. Despite their potential, concerns regarding the safety and specificity of AAV vectors remain. This meta-analysis aims to evaluate the clinical safety and gene-targeting specificity of AAV-based gene therapies by synthesizing data from relevant clinical trials.
Methods: A systematic review was conducted to identify clinical trials utilizing AAV vectors in gene therapies. Data from 55 clinical trials, conducted between 2005 and 2023, were included in the analysis. Outcomes related to adverse events (AEs), immune responses, and gene-targeting specificity were extracted. Meta-analysis using Python and R was performed to compute pooled estimates of safety profiles, with subgroup analyses based on disease type and vector serotypes. Statistical heterogeneity was assessed using I², and publication bias was evaluated through funnel plots.
Results: A total of 3,600 patients were included in the analysis. The pooled incidence of serious adverse events (SAEs) was 4.5% (95% CI: 2.8%-6.1%), with mild to moderate AEs such as injection site reactions and transient liver enzyme elevations reported in 12.3% of cases. Immune responses to AAV vectors were observed in 10.1% of trials but were mostly manageable. Specificity analysis revealed that 88% of therapies achieved target-specific gene expression without significant off-target effects. Subgroup analysis indicated that liver-directed therapies exhibited the highest specificity (92%), while central nervous system-targeted therapies showed moderate off-target risks (15%).
Conclusion : AAV-mediated gene therapies demonstrate a favorable safety profile with manageable immune responses and a high degree of gene-targeting specificity. Although off-target effects remain a concern in certain applications, particularly in the CNS, the overall data supports the continued use and further development of AAV vectors in clinical gene therapy. More long-term safety data is required to assess delayed adverse events.