%0 Journal Article
%T Factors governing the transduction efficiency of adeno-associated virus in the retinal ganglion cells following intravitreal injection
%J -
%D 2019
%R https://doi.org/10.1038/s41434-019-0060-0
%X Efficient transduction of the retinal ganglion cells (RGCs) is a prerequisite to maximize therapeutic outcomes in any form of gene therapy for optic neuropathies. Whereas subretinal injection of adeno-associated virus 2 (AAV2) has been well-characterized, the serotype, viral load, and promoter combinations that govern RGC transduction efficiency following intravitreal injection remains poorly understood. We evaluated the transduction efficiency of seven AAV2 serotypes (AAV2/1, AAV2/2, AAV2/4, AAV2/5, AAV2/6, AAV2/8, and AAV2/9) for the RGCs at 4 weeks following intravitreal injection in C57BL/6J mice. Intravitreal injection of 1£¿¡Á£¿109£¿vg of AAV2/2 with eGFP driven by the CMV promoter attained a higher transduction efficiency for the RGCs (60.0£¿¡À£¿4.2%) compared with the six other AAV2 serotypes with eGFP driven by the same promoter injected at the same viral load (£¿<£¿3.0%). Reporter driven by the CAG promoter had a lower transduction efficiency (up to 42.0£¿¡À£¿5.8%) compared with that driven by the CMV reporter (60.0£¿¡À£¿4.2%, p£¿¡Ü£¿0.024). There was a viral dose-dependent transduction effect of AAV2/2-CMV-eGFP and the transduction efficiency was 40.2£¿¡À£¿3.9%, 16.6£¿¡À£¿4.2%, and 2.6£¿¡À£¿0.2% when the viral load decreased to 5£¿¡Á£¿108£¿vg, 1£¿¡Á£¿108£¿vg, and 1£¿¡Á£¿107£¿vg, respectively. Optimizing viral serotype, viral load, and promoter construct of AAV2 is important to maximize transgene expression in RGC-targeted gene therapy
%U https://www.nature.com/articles/s41434-019-0060-0