Abstract
While many studies have investigated the use of recombinant adeno-associated vectors (rAAV) in the posterior chamber for treatment of inherited retinal diseases, fewer studies have looked at rAAV’s ability to transduce cells within the anterior chamber. This study focuses on evaluating the tropism and tolerability of three rAAV serotypes—rAAV2/6, rAAV2/9, and rAAV2/2[MAX]—expressing a green fluorescent protein (GFP) reporter following intracameral injection in the non-human primate (NHP) African green monkey (Chlorocebus sabaeus) model. Injection of high dose (1 × 1012 vg/eye) rAAV vector resulted in transient inflammation characterized by aqueous flare and cellular infiltrate that resolved without intervention in all serotypes. Post-mortem histology revealed widespread expression of GFP in cells of the trabecular meshwork and iris in high dose rAAV2/6, rAAV2/9, and particularly rAAV2/2[MAX] eyes, indicating that rAAV vectors of these serotypes have broad tropism for cells of the anterior chamber and may facilitate the treatment of blinding disorders, such as glaucoma.
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Acknowledgements
The authors would like to thank David Burke at Oregon Health & Science University for his assistance with the neutralizing antibody assays. We would also like to thank Gavin Marcoe for his assistance in vector manufacturing. In addition, the authors would like to thank the supporting staff at Virscio and the St. Kitts Biomedical Research Foundation.
Funding
This work was funded by intramural support from Medical College of Wisconsin’s Office of Research and NEI R01EY032478.
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Conceptualization: DML, MEO, MSL, KJC. Investigation: KJC, KZI, ZDG, MEO. Writing (Original Draft): KJC, DML, MEO. Writing (Revision and Editing): KJC, DML, MSL, MEO, KZI, ZDG.
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All animal experiments were approved by the Medical College of Wisconsin’s Institutional Animal Care and Use Committee and adhere to the Association for Research in Vision and Ophthalmology statement for the use of animals in ophthalmic and vision research.
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Chern, K.J., Issac, K.Z., Gumbs, Z.D. et al. Tolerability and tropism of recombinant adeno-associated virus vectors in the African green monkey (Chlorocebus sabaeus) anterior chamber. Gene Ther 30, 714–722 (2023). https://doi.org/10.1038/s41434-023-00407-z
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DOI: https://doi.org/10.1038/s41434-023-00407-z
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