In Vivo Alteration of the Keratin 17 Gene in Hair Follicles by Oligonucleotide-Directed Gene Targeting

The study investigated the effects of altering the keratin 17 (K17) gene in hair follicles using oligonucleotide-directed gene targeting in mice. Researchers injected chimeric RNA-DNA oligonucleotides (RDO) and single-stranded oligonucleotides (ssODN) into the skin of C57Bl/6 mice to induce a mutation (R94P) associated with pachyonychia congenita type 2, which affects hair and skin. The mutation led to observable changes such as twisted hair shafts and broken hair follicles, with a 50% reduction in full anagen hair follicles in the treated area. However, these changes were transient, likely due to compensation by other keratins or replacement by normal cells. The frequency of successful gene alteration was below 3%.