Mutation-Targeted siRNA Therapy for Connexin 26-Associated Keratitis-Ichthyosis-Deafness Syndrome

ConclusionTo that end, a KID syndrome cell line (KID-KC) was established from primary keratinocytes of a KID syndrome patient with heterozygous p.D50N mutation, which displayed impaired gap junction intercellular communication and hyperactive hemichannels, confirmed by dye transfer, patch clamp and neurobiotin uptake assays. In KID-KCs, treatment with AS-siRNA led to robust inhibition of the mutant GJB2 allele without altering expression of the wildtype allele. This resulted in correction of both gap junction intercellular communication and hemichannel activity. Furthermore, AS-siRNA treatment caused only low-level off-target effects in KID-KCs, as detected by genome-wide RNA sequencing. Our data provide an important proof-of-concept for the potential use of AS-siRNA in treating KID syndrome, and in other genetic conditions due to dominant mutations.
Source: Cytotherapy - Category: Cytology Source Type: research