Although the majority of hereditary hearing loss is non-syndromic, many genetic syndromes also cause deafness, including neurofibromatosis type 2 and Usher syndrome. In addition, age-related hearing loss is thought to have a genetic component (SNPs rs4932196 and rs58389158), although the exact genetic cause(s) of the disease is still being elucidated (PLoS Genet. 2016;12:e1006371).
The discovery of genetic mutations has come with a whole host of potential genetic therapies; however, “the dominant deafness genes cannot be corrected with gene replacement strategies, so researchers are turning to gene-editing approaches to correct those types of hearing losses: either silencing RNA (siRNA) or CRISPR strategies,” said Hinrich Staecker, MD, PhD, the David and Mary Zamierowsky Professor of otolaryngology at the University of Kansas School of Medicine in Kansas City.
CRISPR, which stands for clustered regularly interspaced short palindromic repeats, uses the Cas9 enzyme to cut a specific target sequence on a mutant gene—cutting both strands of the DNA. Repair enzymes can then be inserted to repair and seal the cut with new genetic information, permanently changing the underlying genetic code. A landmark study in Nature reported the results of using CRISPR-Cas9 to correct a mutation in a gene that causes hypertrophic cardiomyopathy in human embryos (Nature. 2017;548:13–14). Researchers have questioned the findings of that study, however (see “Landmark Gene-Editing Study Called into Question,”).