In research supported by the Usher 1F Collaborative, Genetic Cures Australia, and NIDCD/NIH, a group of researchers studied how to deliver a gene therapy to mice with mutations in the PCDH15 gene, which causes USH1F. The current method of delivering gene therapy to the retina is via an AAV vector (Adeno-associated Virus). This is the technology used in the gene therapy, Luxturna, for Leber congenital amaurosis. However, this method of delivery cannot be used to treat mutations in PCDH15 due to the large size of the gene which exceeds the capacity of AAVs. These researchers tested whether using a dual-AAV system could overcome this barrier, which involves splitting the PCDH15 gene into two parts and packaging them in two AAVs before delivering them to the retina of mice. Following this, they were able to show that PCDH15 was expressed efficiently and visual function was rescued in the mice with USH1F who had been treated with the dual-AAV-based gene therapy.
What this means for Usher syndrome: Further research into the potential use of dual-AAV delivery could foster development of a gene therapy to treat vision impairment in Usher 1F. A solution for packaging large genes would overcome one barrier to gene therapy for Usher syndrome 1F, and Usher syndrome caused by mutations in other large genes like MYO7A (USH1B), CHD23 (USH1D), and USH2A.
