AAV ShH10-CAG-GFP

Müller glia are the major cellular component of the retina and participate in a variety of roles that are critical for retinal function, such as providing structural, nutritional, homeostatic, osmotic, metabolic, and growth factor support to retinal neurons. These glial cells also interact with blood vessels, participate in the function of the blood-retinal barrier, and regulate retinal blood flow. Several gene mutations expressed in Müller glia have been associated with retinal dystrophies. Therefore, Müller glia have been proposed as a target for therapeutic approaches to retinal diseases, such as gene replacement therapy or promoting the secretion of neurotrophic factors to enhance their neuroprotective effects. Several different adeno-associated viruses (AAVs) have been shown to have tropism for Müller cells. A novel variant, named ShH10, showed a significant increase in transduction efficiency and specificity for Müller cells compared to the very low transduction efficiency of the parental AAV6. ShH10 was able to produce diffuse expression throughout the retina, with approximately 94% of the transduced cells being Müller cells, and only 2% of interneurons and 4% of retinal ganglion cells being transduced to some extent. In contrast, about 76% of the transduced cells with AAV2 were Müller cells, while 3% of interneurons and 21% of retinal ganglion cells were transduced to some extent. ShH10 also transduced Müller cells more efficiently, with ShH10 transducing 22% of Müller cells compared to 14% with AAV2.