- Scientists develop a single solution of genome editing agent that partially preserves hearing ability.
- They have applied this strategy to a mouse model of progressive hearing loss.
- After 4 weeks, treated mice responded to 65 dB of sound, whereas untreated mice responded to sound starting at 80 dB.
One of the common types of sensory loss in humans is hearing loss. In the United Kingdom alone, there are about 11 million people (1 in every 6 people), who suffer with hearing loss, and nearly half of these cases fall under genetic cause.
No permanent treatment has long been discovered probably because of lack of right technology. However a new study done by Howard Hughes Medical Institute, Harvard and MIT researchers holds a promise of healing human genetic progressive deafness.
They have developed a single solution of a genome editing agent that partially preserved hearing ability in mice with genetic deafness. This is a huge success, and one day it could help researchers treat specific types of genetic hearing loss in humans.
One of the genetic mutation that affects hearing is called “Tmc1”. Even a slight error in this gene could cause the loss of inner hair cells of the ear over time (in both mice and human). These cells are responsible for detecting sounds and then converting the information into nerve signals, which travels to the brain.
According to the research team, destroying the gene’s mutated copy (known as “Beethoven” in mice) could preserve some hearing.
The team developed a therapy that injects a CRISPR-Cas9 gene editing protein complex directly into the sound sensing cells, for disrupting a mutation. This is done to stop the progression of genetic hearing loss.
Injecting Cas9 protein locally, rather than DNA elements which can be used by the cell to build Cas9, enhanced the safety of the treatment and improved DNA specificity.
Since the mutated Tmc1 gene and its regular counterpart only differ by a single DNA letter, Cas9 must target the mutated gene with laser accuracy, otherwise it would simply disable or harm the functional copy of the gene instead.
In order to improve the editing precision, the team worked on cationic lipid-mediated delivery of proteins. Usually, scientists insert the Cas9 DNA encoding into the cell, and allow it to generate the gene-editing arsenal on its own.
However, the team showed that if Cas9 gene-editing complex itself is injected into a cell, bundled inside lipids envelope, the editing is much more accurate. Cas9 degrades immediately, cutting its target preciously before proceeding to edit off-target DNA strands. Furthermore, the therapeutic effect via local inner ear delivery helps to reduce the potential risks.
What Are Genome Editing and CRISPR-Cas9?
Genome (gene) editing represents a set of technologies that allows scientists to alter the DNA of an organism. These technologies help scientists to add, change, or remove a genetic material at certain locations in the genome.
Numerous methodologies have been developed to perform genome editing, and one of them is CRISPR-Cas9. It stands for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9. It’s more accurate, cheaper, faster, and more efficient as compared to other techniques.
Without treatment, the sound-detecting bristles in the inner ear of mice disappear (white box, right)
For now, they have applied this strategy to a mouse model with progressive hearing loss. The treated mice maintained a significant amount of hearing compared to those who left untreated.
Specifically, treated mice responded to 65 decibels of sound, whereas untreated mice responded to sound starting at 80 decibels, after 4 weeks.
Among edited cells, genetic sequencing displayed that Tmc1 mutated copy had successfully disrupted nearly 94% of the time. After 8 weeks, treated mice responded to sudden loud, while the untreated mice didn’t able to do that.
The research team plans to build and test the therapy in larger animal models. They are also working to ensure the method remains safe and effective. There is still a lot of work to do with this strategy before applying it to human, but at this moment, scientists are delighted and excited that it worked on the animal model.