JUN 11, 2020 6:14 PM PDT

Restoring Hearing by Editing Only One Base of a Gene

WRITTEN BY: Carmen Leitch

Errors in genes can cause serious diseases. Some of those errors are large, while others are due to a change in only one letter or base of a gene's sequence. Scientists have taken aim at these single-base pair changes, and developed a gene editor that works by simply switching one base to another. Researchers have now applied this editor to repair a mutation in a gene called Tmc1, which is a known cause of hereditary deafness. This work, which was reported in Science Translational Medicine, is also the first example of gene editing that repairs a recessive instead of a dominant mutation.

A laser scanning confocal microscope image of the mouse cochlea, the inner ear hearing organ. Sensory cell bodies are stained in blue, sensory organelles in red, and cells with repaired Tmc1 gene in green. / Credit: Olga Shubina-Oleinik, Boston Children's Hospital

"Most genetic diseases are not caused by dominant mutations, they're caused by recessive ones, including most genetic hearing losses," said David R. Liu, Thomas Dudley Cabot Professor of the Natural Sciences and a member of the Broad Institute and the Howard Hughes Medical Institute.

Dominant mutations are those in which only one of the body's two copies of a gene is mutated, and that mutated form dominates the normal one and causes a disease. If the mutant copy can be removed or silenced through gene therapy, the normal copy can then step in and perform the gene's function.

"But for recessive diseases," Liu said, "you can't do that. By definition, the recessive allele means that you have two bad copies. So, you can't just destroy the bad copy." One or both of the bad copies has to be repaired.

Study co-author Wei Hsi (Ariel) Yeh, who was inspired to pursue this work after a friend inexplicably went deaf, spent years creating an editor that could identify the erroneous base and fix it. But once it was made, it was too big to fit into the delivery system that would carry it to the genome, and it had to be broken in two. However, the technique worked efficiently, and there were few instances of unintended edits.

"We saw very little evidence of off-target editing," Liu said. "And we noticed that the edited animals had much-preserved hair cell morphology and signal transduction, meaning the hair cells, the critical cells that convert sound waves to neuronal signals appeared more normal and behaved more normally."

More work will be needed before this is proven to be a safe and effective treatment for humans, but the researchers want to prove its efficacy not only for deafness due to recessive Tmc1 mutations. It may be useful in helping patients with progeria or sickle cell anemia.

"We're actually going after quite a few genetic diseases now, including some prominent ones that have caused a lot of suffering and energized pretty passionate communities of patients and patient families to do anything to find a treatment," Liu said. "For progeria, there's no cure. The best treatments extend a child's average lifespan from about 14 to 14.5 years."

Sources: AAAS/Eurekalert! via Boston Children's Hospital, Harvard University, Science Translational Medicine

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
AUG 04, 2020
Genetics & Genomics
A Hybrid Animal - the Sturddlefish - Is Created
AUG 04, 2020
A Hybrid Animal - the Sturddlefish - Is Created
Scientists, for reasons that are unclear, mixed eggs and sperm from two different species of fish and ended up creating ...
AUG 18, 2020
Genetics & Genomics
Autism is Linked to Abnormal Lipid Levels
AUG 18, 2020
Autism is Linked to Abnormal Lipid Levels
Scientists have found a cluster of genes that plays a role in the development of an autism subtype. The genes are involv ...
AUG 24, 2020
Genetics & Genomics
Towards a Cure for Latent Herpes 1 Infections
AUG 24, 2020
Towards a Cure for Latent Herpes 1 Infections
Herpes simplex virus 1 (HSV-1) causes what's popularly known as cold sores, and is transmitted mostly through oral-t ...
OCT 14, 2020
Genetics & Genomics
Robots Are Moving Developmental Biology Forward
OCT 14, 2020
Robots Are Moving Developmental Biology Forward
Researchers have created a robot that can analyze the effects of mutations that occur in portions of the genome that hel ...
OCT 15, 2020
Plants & Animals
Meet the World's First Cloned Przewalski's Horse
OCT 15, 2020
Meet the World's First Cloned Przewalski's Horse
Say “hello!” to Kurt, a two-month-old Przewalski’s horse that has made scientific history as the world ...
OCT 29, 2020
Genetics & Genomics
Severe Genomic Damage in Human Embryos Treated With CRISPR
OCT 29, 2020
Severe Genomic Damage in Human Embryos Treated With CRISPR
The CRISPR-Cas9 genomic editing system holds great promise for treating genetic errors that cause human disease. But we ...
Loading Comments...