Genetic anomalies are responsible for nearly half of all hearing disorders and an inordinate number of other diseases. Many of these genetic issues are congenital, and until now, their progression has mainly been inevitable. Thanks to gene editing, that may soon change.
As reported by Harvard News two years ago, researchers Wei Hsi Yeh and Thomas Dudley Cabot were able to repair a genetic mutation in a Beethoven Mouse using the CRISPR Cas-9 gene editing system. So named because it leverages DNA sequences from single-celled organisms, this treatment can target and remove specific DNA segments, cutting both DNA strands and allowing bases to be inserted, removed, or rearranged.
Beethoven Mice suffer from the same genetic mutation responsible for progressive hearing loss in humans. Via Cas9, the researchers were able to identify the defective copy of the hearing gene TMC1 and disable it, sparing the healthy counterpart. This restored partial hearing to the animal.
Although there’s a long road ahead before this kind of therapy can be used in humans, the implications are enormous. But the process itself is also complex enough to make one’s head spin. Let’s see if we can’t demystify a few things.
First, let’s talk about dominant vs. recessive gene mutations. There are two copies of every gene in the human body. With a dominant mutation, only a single copy of the gene is defective.
As you might expect, this is simple to fix (relatively speaking). All one needs to do is eliminate the faulty gene, and the remaining gene will overcompensate to make up for it. If it helps, a good analogy to think of would be when someone has a kidney removed; their body can still function with a single kidney.
When a mutation is recessive, that means both copies of a gene are defective or mutated. This is much harder to correct, as you cannot simply destroy or remove one of the genes. You need to repair them both.
Base editing is currently one of the best techniques for this. Unlike Cas9, this technology chemically modifies DNA strands, specifically targeting point mutations; errors found in nucleotides, the most basic building blocks of DNA. Typically, this is achieved through the use of Adeno-Associated Viruses, artificially modified viral cells designed to attach to specific gene sequences.
Base editing is possibly one of the most promising technologies in gene editing at the time of writing, with near-flawless precision. Although there is still some margin of error (known as off-target editing), for the most part, base editing seems to have the potential to treat a wide range of genetic disorders. The potential applications are nearly limitless. Once the technique has been perfected enough to be used in humans, it could make genetic hearing disorders — or realistically, all genetic disorders — a thing of the past.