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Updated: May 11, 2025
Subconjunctival Administration of Adeno-associated Virus Vectors in Small Animal Models
Published on: March 16, 2022
The clinical safety landscape for ocular AAV gene therapies: A systematic review and meta-analysis
Zishi Liu1,2, Haoliang Zhang1,2, Huixun Jia1,2,3,4
1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Adeno-associated virus (AAV) gene therapy is a promising approach for treating ocular monogenic or acquired diseases, though immunogenicity and safety remain critical considerations. We conducted a systematic review of 120 trials and 32 publications to assess immune responses across different delivery routes. Intravitreal administration was associated with higher rates of anterior uveitis (43.06% vs. 10.22%) and intermediate/posterior uveitis (40.36% vs. 6.18%) compared to subretinal delivery. Engineered AAV capsids, used exclusively in intravitreal studies, showed no significant difference in either type of uveitis incidence compared to natural serotypes. Prophylactic immunosuppression (PI) did not affect ocular or systemic immune responses in subretinal delivery, but significantly reduced systemic immune responses in intravitreal administration. These findings underscore the potential of PI to mitigate systemic immune responses in intravitreal AAV therapy. This review should help guide the choice of routes of administration and immunosuppression strategies, and highlights current trends in ocular AAV gene therapy.
Adeno-associated virus (AAV) gene therapy is a promising approach for treating ocular monogenic or acquired diseases, though immunogenicity and safety remain critical considerations. We conducted a systematic review of 120 trials and 32 publications to assess immune responses across different delivery routes. Intravitreal administration was associated with higher rates of anterior uveitis (43.06% vs. 10.22%) and intermediate/posterior uveitis (40.36% vs. 6.18%) compared to subretinal delivery. Engineered AAV capsids, used exclusively in intravitreal studies, showed no significant difference in either type of uveitis incidence compared to natural serotypes. Prophylactic immunosuppression (PI) did not affect ocular or systemic immune responses in subretinal delivery, but significantly reduced systemic immune responses in intravitreal administration. These findings underscore the potential of PI to mitigate systemic immune responses in intravitreal AAV therapy. This review should help guide the choice of routes of administration and immunosuppression strategies, and highlights current trends in ocular AAV gene therapy.
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