AAV8-hGRK1-HA-mini-PCDH15v4

AAV8-hGRK1-HA-mini-PCDH15v4 is an adeno-associated virus (AAV) serotype 8-based gene therapy designed to treat blindness associated with Usher syndrome type 1F (USH1F). USH1F is caused by mutations in the *PCDH15* gene, which encodes protocadherin-15, a protein essential for the structural integrity of hair cell stereocilia in the inner ear and calyceal processes in retinal photoreceptors. Because the full-length *PCDH15* coding sequence (~5.8 kb) exceeds the standard AAV packaging capacity, this therapy utilizes a "mini-PCDH15" transgene (version 4) that removes five of the eleven extracellular cadherin repeats while maintaining therapeutic function. The construct is driven by the human G-protein-coupled receptor kinase 1 (hGRK1) promoter to ensure specific expression in rods and cones. Developed through a collaboration between Harvard Medical School and Spark Therapeutics, the therapy has demonstrated the ability to localize correctly to calyceal processes and show safety in non-human primate models.

Other names

mini-PCDH15 gene therapymini-PCDH-15 gene therapymini-PCDH 15 gene therapyAAV8-hGRK1-HA-mini-PCDH15AAV-8-hGRK1-HA-mini-PCDH15AAV 8-hGRK1-HA-mini-PCDH15