CRISPR-Cas9 a Potential Treatment for Hereditary Deafness

CRISPR-Cas9 a Potential Treatment for Hereditary Deafness

A new treatment for hereditary deafness is a giant step closer thanks to the gene editing tool, CRISPR-Cas9.

Scientists at the Howard Hughes Medical Institute have conducted a study on mice that saw a rare form of hereditary deafness treated with a single dose of CRISPR-Cas9.

The study was performed on mice with a mutation in the Tmc1 gene, also known as the Beethoven gene. The single-base mutation results in the production of a toxic protein which destroys inner ear hair cells, which are required to sense sound waves. Over time, more and more hair cells are killed, resulting in progressive deafness. The gene mutation is responsible for 8% of cases of genetic hearing loss in humans.

Several weeks after receiving a single dose of the CRISPR-Cas9 treatment, mice were assessed. Mice that had received the treatment maintained a startle response to loud noises and were able to hear sounds at a level of 15 decibels lower than untreated mice. Analysis of the hair cells showed them to be full and normal, whereas mice that had not received the treatment showed signs of hair cell damage.

This is not the first time that researchers have used gene editing as a treatment for hereditary deafness. A team of researchers at Boston Children’s Hospital and Harvard Medical School were able to restore hearing loss in mice using gene therapy to add in a functional copy of the TMC1 gene. However, this is the first time that gene therapy has been used to disrupt the function of a defective DMC1 gene instead of replacing it.

Further, the genetic mutation that was corrected by the Howard Hughes Medical Institute is dominant, meaning a mutation in just one of the gene pairs will lead to deafness. Dominant mutations cannot be corrected with other forms of gene therapies.

CRISPR-Cas9 is currently still being researched and the gene editing tool remains largely untested in humans. However, numerous in vitro studies have been performed and the technique has shown highly promising results in animal.

The system can be used to make highly specific cuts to DNA using mRNA as a guide to bind onto a very specific section of the DNA. The Cas9 enzyme is then used to make the cut. The system can be used to make edits to DNA, or to remove or add new sections of DNA to replace or repair defective genes. The system is relatively low cost and studies indicate there are little to no off-target effects. The gene editing tool is therefore being hailed as a potential cure for a wide range of genetic defects.

The latest research adds to the growing body of evidence showing the effectiveness of the technique, although human trials are still some way off. The scientists will need to conduct further research before it is known whether they can use CRISPR-Cas9 as a treatment for hereditary deafness in humans, but the team is confident in the technology.

HHMI chemical biologist David Liu said, “We hope that the work will one day inform the development of a cure for certain forms of genetic deafness in people,” with the treatment most likely to be most effective in children carrying the Tmc1 mutation who have not yet experienced major hearing loss.

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