Ultrasound-Enhanced Retinal Delivery of Engineered Viral Vectors
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Updated: Nov 4, 2026
Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium
Published on: August 7, 2015
Schuyler Link1,2,3, Kara Fan4, Jesus Adame4
1Department of Bioengineering, Rice University, Houston, Texas, United States.
Purpose:
The goal of this study was to examine focused ultrasound blood-retina barrier opening (FUS-BRBO) as a method to deliver gene therapy to the eye. We compared AAV.FUS.3, an engineered variant optimized for FUS-enhanced delivery to the central nervous system, and AAV9 for their utility as neuronal gene vectors.
Methods:
Mouse eyes were insonated by 4.667 MHz FUS in a custom-designed nosecone. Evans blue dye was administered intravenously to verify the presence of blood-retina barrier opening. Once BRBO was demonstrated, viral vectors were administered before ultrasound scanning to allow crossing into the retina. Viral tropism among different cell types was analyzed, and structural changes were investigated.
Results:
FUS-BRBO was achieved across a range of pressures. FUS-BRBO allowed for retinal transduction of systemically administered viral vectors. 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. No gross tissue damage was noted.
Conclusions:
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. Further research to improve efficiency of delivery to the outer retina could expand utility of FUS-BRBO.
