Template-independent genome editing in the Pcdh15 mouse, a model of human DFNB23 nonsyndromic deafness.

Although frameshift mutations lead to 22% of inherited Mendelian disorders in humans, there is no efficient in vivo gene therapy strategy available to date, particularly in nondividing cells. Here, we show that nonhomologous end-joining (NHEJ)-mediated nonrandom editing profiles compensate the frameshift mutation in the Pcdh15 gene and restore the lost mechanotransduction function in postmitotic hair cells of Pcdh15 mice, an animal model of human nonsyndromic deafness DFNB23. Identified by an ex vivo evaluation system in cultured cochlear explants, the selected guide RNA restores reading frame in approximately 50% of indel products and recovers mechanotransduction in more than 70% of targeted hair cells.

Hearing loss is an early biomarker in APP/PS1 Alzheimer's disease mice.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive loss of memory and cognitive decline. Over the last decade, it has been found that defects in sensory systems could be highly associated with AD. Hearing is an important neural sense.