One important factor in gene delivery is developing altered cell tropisms to narrow or broaden rAAV-mediated gene delivery and to increase its efficiency in tissues. Specific properties like capsid conformation, cell targeting strategies can determine which cell types are affected and also the efficiency of the gene transfer process. Different kinds of modification can be undertaken. For example, modification by chemical, immunological or genetic changes that enables the AAV2 capsid to interact with specific cell surface molecules.
Initial studies with AAV in the retina have utilized AAV serotype 2. Researchers are now beginning to develop new variants of AAV, based on naturally-occurring AAV serotypes and engineered AAV variants.
Several naturally-occurring serotypes of AAV have been isolated that can transduce retinal cells. Following intravitreal injection, only AAV serotypes 2 and 8 were capable of transducing retinal ganglion cells. Occasional Muller cells were transduced by AAV serotypes 2, 8, and 9. Following subretinal injection, serotypes 2, 5, 7, and 8 efficiently transduced photoreceptors, and serotypes 1, 2, 5, 7, 8, and 9 efficiently transduce RPE cells.
One example of an engineered variant has recently been described that efficiently transduces Muller glia following intravitreal injection, and has been used to rescue an animal model of aggressive, autosomal-dominant retinitis pigmentosa.