Mutated AAV2-Based Vector for Efficient Transduction of Photoreceptors and Retinal Pigment Cells

Technology #15100

Improves Delivery of Transgenes to Photoreceptors and Retinal Pigment Cells upon Injection

This AAV2-based capsid variant achieves higher transduction of photoreceptors and retinal pigment cells following subretinal injection. This AAV2-based vector could therefore improve the efficiency of retinal gene therapy by increasing transduction of retinal cells after injection. AAV vector-based therapy has proven to be useful in treating a number of diseases, including congestive heart failure, Parkinson’s disease, hemophilia, and dry age-related macular degeneration, by delivering therapeutics to targeted cells. Unfortunately, the transduction efficiency of AAV-based vectors varies depending on the targeted cells and tissues. Cellular proteins can inhibit wild-type AAV-based vectors and consequently decrease the efficiency of the gene therapy. University of Florida researchers have developed a mutated AAV2-based vector that contains capsid mutations that help the vector avoid this cellular inhibition. In addition, this vector lacks canonical heparan sulfate binding residues, a feature that also contributes to the observed increases in retinal transduction. Transduction by this variant is as efficient as that achieved by AAV5 or AAV8, two serotypes typically used to target the outer retina following subretinal injection.


Mutated AAV2-based vector gene therapy for more efficient transduction of retinal cells


  • Administers a mutated AAV2-based vector, enhancing photoreceptor and retinal pigment cells transduction following subretinal injection
  • Transduction by this variant is akin to that achieved by other well characterized serotypes such as AAV5 and AAV8, increasing the accessibility of gene therapies and simplifying patient treatment


AAV vector-based therapy has been utilized in treating a number of diseases; however, wild-type AAV-based vectors can be inhibited by cellular proteins. This gene therapy targets retinal cells by incorporating mutations on the AAV2 capsid surface which help the vector avoid this cellular protein inhibition. Additional capsid mutations ablate binding to heparan sulfate. This variant transduces photoreceptors and retinal pigment cellsmore efficiently then wild-type AAV2-based vectors and achieves results akin to “photoreceptor-phillic” serotypes AAV5 or AAV8. The AAV2-based vector treatment can be accomplished via subretinal injection.