Correction of Hair Shaft Defects Through Allele-Specific Silencing of Mutant Krt75

    September 2015 in “ Journal of Investigative Dermatology ”
    Ying Liu, Elizabeth R. Snedecor, Xu Zhang, Yanfeng Xu, Lan Huang, Evan Jones, Lianfeng Zhang, Richard A.F. Clark, Dennis R. Roop, Chuan Qin, Chen Chen Jiang
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    TLDR Using special RNA to target a mutant gene fixed hair problems in mice.
    The document from 2016 describes a study where allele-specific small interfering RNAs (siRNAs) were used to selectively suppress a mutant form of the Krt75 gene, which causes hair shaft defects in mice. The study showed that hair regenerated from mutant Krt75 mouse cells exhibited defects when grafted, but these defects were suppressed when the cells were treated with a lentiviral vector expressing mutant Krt75-specific short hairpin RNA (shRNA). This led to a significant reduction in mutant Krt75 mRNA and corrected the hair structural phenotype. The study suggests that RNA interference can be used to durably correct hair defects caused by mutant keratin genes and offers a potential therapeutic approach for disorders related to keratin mutations. Safety concerns regarding the use of lentiviral vectors were acknowledged, highlighting the need for safer therapeutic siRNA delivery methods.
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