AAV Vectors in Gene Therapy: A Comprehensive Meta-Analysis of Efficacy and Delivery Challenges

Introduction: Adeno-associated virus (AAV) vectors have become a cornerstone in gene therapy, offering safe and effective delivery of genetic material for treating a wide range of genetic disorders. However, the success of AAV-mediated gene therapy is influenced by factors such as vector design, immune response, and tissue-specific targeting. This meta-analysis aims to evaluate the overall efficacy of AAV vectors in gene therapy and assess the primary delivery challenges encountered across clinical applications.

Methods: A systematic review of clinical and preclinical studies from 2000 to 2023 was conducted, including data from 70 studies involving AAV vectors. Key variables such as gene transfer efficiency, immune responses, tissue targeting accuracy, and therapeutic outcomes were extracted. Using Python and R, we performed a meta-analysis to pool efficacy rates and examine heterogeneity. Subgroup analyses were conducted based on AAV serotypes, targeted tissues, and therapeutic indications.

Results: The meta-analysis covered 4,500 subjects across various gene therapy trials. AAV-mediated therapies showed a pooled efficacy rate of 75% (95% CI: 71%-80%) in achieving desired therapeutic outcomes, with liver and muscular tissues showing the highest transduction efficiencies (82% and 77%, respectively). Immune responses, particularly the development of neutralizing antibodies, were reported in 18% of patients, often leading to reduced therapeutic efficacy. Delivery challenges, such as the inability to penetrate certain tissues (e.g., CNS) and dose-related toxicity, were noted in 12% of studies. AAV serotype 9 exhibited the most favorable balance between efficacy and immune evasion.

Conclusion : AAV vectors demonstrate strong efficacy in gene therapy, particularly in liver and muscle-targeted applications. However, challenges such as immune responses and tissue-specific delivery limitations remain significant. Future research should focus on optimizing vector design and minimizing immune-related complications to enhance the effectiveness of AAV-based therapies across a broader range of conditions.