1. Preclinical studies for a retinoschisis clinical trial: We are currently evaluating the immune response to vector after intravitreal injection and are in the process of refining a transient immune suppression protocol. The vector design is be optimized for efficiency. 2. Retinitis Pigmentosa due to RPGR mutation: Animal models and vectors are being constructed and evaluated. 3. CEP290: Vectors have been prepared for this project and are being tested in vivo for expression and efficacy. This project has been expanded to examine several strategies for vector construction. The problem is that the CEP290 gene is 7.4 kb in length and AAV vectors can only package about 5 kb. A claim that AAV type 5 vectors could package intact vector genomes in the 8-9kb range was tested and was not supported by the data. A manuscript describing our results was published this year. We are now evaluating lentiviral vectors and compacted DNA particles as potential alternative gene transfer vehicles. 4. Improved therapeutics for neovascular diseases: In collaboration with Dr. Carmen Clapp of the Universidad Nacional Autonoma de Mexico, Juriquilla campus, we are examining a novel anti-angiogenic fragment of prolactin, called vasoinhibin, in the context of AAV vectors. AAV vectors encoding vasoinhibin, prolactin, and sFlt-1 (a soluble VEGF receptor fragment that acts as a competitive inhibitor) have been produced and have been tested in an animal model of diabetic retinopathy. These studies have been successful and a manuscript is being prepared. A new project examining the role that PDGF-C plays in the neovascular response has been initiated with Dr. Xuri Li of the National Eye Institute. Vectors have been made and we are waiting for the results of animal studies. 5. Vectors with transcytosis activity and low preexisting immunity in humans: This work is on-going.
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