PCDH15, the gene that causes Usher syndrome type 1F (USH1F), is too large to fit into viruses usually used for gene therapy. As a result, a group of researchers attempted to create a smaller version of the gene that could fit into the viruses. The researchers removed a part of the gene that encodes repeated domains of the protein while trying to maintain the shape and function of the protein. They created eight versions of the smaller gene and tested them in the ears of mouse models. Most of the smaller versions of PCDH15 appeared to bind normal protein binding partners in the cochlea.
The researchers then tested the smaller PCDH15 genes in profoundly deaf USH1F mouse models. One mini-gene showed significant restoration of auditory function and restored structure of hair cells, although the electrical responses to sounds were not completely normal.
What this means for Usher syndrome: This paper demonstrates that a smaller PCDH15 gene that fits in gene transfer viruses can be transfected into the cochlea. This result indicates a potential avenue of gene therapy for hearing loss. This approach might also be applicable to other genes.
