Evaluation of human miniPCDH15s in Human Inner Ear Organoids to treat USH1F
Usher syndrome type 1F (USH1F) causes deafness and blindness due to mutations in the protocadherin-15 gene (PCDH15). A simple gene addition therapy for USH1F remains challenging because the PCDH15 coding sequence is too large for adeno-associated virus (AAV) vectors. To overcome this limitation, the team developed “mini”-PCDH15 versions that fit into a single AAV capsid and can restore hearing and balance in mouse models of USH1F. Dr. Indzhykulian will test similarly designed human mini-PCDH15 versions to evaluate their function in human inner-ear organoids. This study will provide a proof-of-concept, preclinical evaluation of human mini-PCDH15s, an essential step for clinical translation.