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We compared AAV.FUS.3, an engineered variant optimized for FUS-enhanced delivery to the central nervous system, and AAV9 for their utility as retinal gene vectors. To achieve this, mouse eyes were insonated by 4.667 MHz FUS in a custom-designed nosecone and vectors administered intravenously. We found 2.1-fold improvement of transduction of AAV.FUS.3 over AAV9 in the insonated area and 19.5-fold improvement over the uninsonated retina. Within that area, the ganglion cell layer showed the highest levels of transduction at 22% for AAV.FUS.3. We observed no gross tissue damage, change in retinal layer thickness, or increase in inflammation markers within the retina. FUS-BRBO has the potential to non-surgically deliver AAV-based vectors to spatially-defined regions of the retina. AAV.FUS.3 showed significantly improved transduction over AAV9 at the same dose. 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