Hearing is believing in gene therapy's promise

December 20, 2017

HOUSTON - (Dec. 20, 2017) - Gene editing could someday help people at risk of hearing loss from genetic mutations, according to research by a new Rice University faculty member.

Xue (Sherry) Gao, who joined Rice in the fall as the Ted N. Law Assistant Professor of Chemical and Biomolecular Engineering, is co-lead author of a new Nature paper that reports on the promise of gene editing to treat autosomal dominant hearing diseases.

Gao performed the research while a postdoctoral associate under the guidance of David Liu at Harvard University. She said that while hearing diseases are typically not life-threatening, hearing loss is the most common human sensory impairment and has a substantial impact on individuals and society.

Many genetic mutations affect the sensory hair cells that amplify acoustic vibrations and translate them into electrical nerve signals. Gao said humans are born with about 12,000 hair cells that do not regenerate spontaneously if damaged. It has been reported that one in every 1,000 infants born in the United States has genetic mutations that contribute to deafness. Nevertheless, she said, few treatments are available to slow or reverse genetic deafness.

The researchers used rodent models of human genetic disease since a rodent cochlea -- the organ in the inner ear that sends sounds to the brain -- is strikingly similar to that of humans, Gao said. They focused on editing hair cells inside the cochlea, which they found suitable for the delivery of one-time, nonreplicable edits through Cas9/single-guide RNA. The RNA is a ribonucleotide (RNP) protein complex designed to specifically disrupt genes associated with hearing loss.

"Delivering the RNP complex instead of DNA into the cochleae showed significantly fewer off-target effects," Gao said. This enabled the researchers to effectively disrupt one genomic site containing a single point mutation and avoid the billions of other sites available for modification.

Eight weeks after injecting the protein complex into the cochleae of rodents with progressive, genetic hearing loss, the researchers observed higher hair cell survival rates compared with those in a control group that did not receive the injection.

Tests that measured brain waves in response to audio cues showed the treatment significantly preserves the animals' hearing compared with the control group. The treatment also helped preserve the injected animals' acoustic behavioral reflexes, according to the researchers. "We believe this is a leading study on using Crispr-Cas9 genome editing technology to treat genetic hearing diseases," said Gao, whose lab is at Rice's BioScience Research Collaborative. "We hope to develop more advanced genome-editing tools and test them on other animal species to demonstrate their safety and effectiveness as we move them toward humans.

"I'm definitely looking for collaborators at Rice, the Texas Medical Center and in Houston who also are interested in developing genome-editing technology," she said.

Gao's primary collaborators on the Nature paper were co-lead author Yong Tao and Zheng-Yi Chen of the Massachusetts Eye and Ear Infirmary.

The Defense Advanced Research Projects Agency and the National Institutes of Health supported the research.
-end-
Editor's note: Links to high-resolution images for download appear at the end of this release.

David Ruth
713-348-6327
david@rice.edu

Mike Williams
713-348-6728
mikewilliams@rice.edu

Read the abstract at http://dx.doi.org/10.1038/nature25164

Read Nature's News & Views "An ode to gene edits that prevent deafness": http://dx.doi.org/10.1038/d41586-017-08645-z

This news release can be found online at http://news.rice.edu/2017/12/20/hearing-is-believing-in-gene-therapys-promise/

Follow Rice News and Media Relations via Twitter @RiceUNews

Related materials:

The Gao Laboratory: http://gaolab.rice.edu

Liu Group: http://evolve.harvard.edu

Rice Department of Chemical and Biomolecular Engineering: https://chbe.rice.edu/

Images for download:

http://news.rice.edu/files/2017/12/0108_HEARING-2-WEB-2n7kobu.jpg

In a new Nature paper, a Rice University professor outlines a strategy that uses gene editing to slow the progression of a genetic hearing disease. (Credit: Illustration by Xue (Sherry) Gao)

http://news.rice.edu/files/2017/12/0108_HEARING-1-WEB-27t0xep.jpg

Xue (Sherry) Gao. (Credit: Tommy LaVergne/Rice University)

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,879 undergraduates and 2,861 graduate students, Rice's undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for quality of life and for lots of race/class interaction and No. 2 for happiest students by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl.com/RiceUniversityoverview.

Rice University

Related Hearing Loss Articles from Brightsurf:

Proof-of-concept for a new ultra-low-cost hearing aid for age-related hearing loss
A new ultra-affordable and accessible hearing aid made from open-source electronics could soon be available worldwide, according to a study published September 23, 2020 in the open-access journal PLOS ONE by Soham Sinha from the Georgia Institute of Technology, Georgia, US, and colleagues.

Ultra-low-cost hearing aid could address age-related hearing loss worldwide
Using a device that could be built with a dollar's worth of open-source parts and a 3D-printed case, researchers want to help the hundreds of millions of older people worldwide who can't afford existing hearing aids to address their age-related hearing loss.

Understanding the link between hearing loss and dementia
Scientists have developed a new theory as to how hearing loss may cause dementia and believe that tackling this sensory impairment early may help to prevent the disease.

Study uncovers hair cell loss as underlying cause of age-related hearing loss
In a study of human ear tissues, scientists have demonstrated that age-related hearing loss is mainly caused by damage to hair cells.

Hair cell loss causes age-related hearing loss
Age-related hearing loss has more to do with the death of hair cells than the cellular battery powering them wearing out, according to new research in JNeurosci.

How hearing loss in old age affects the brain
If your hearing deteriorates in old age, the risk of dementia and cognitive decline increases.

Examining associations between hearing loss, balance
About 3,800 adults 40 and older in South Korea participating in a national health survey were included in this analysis that examined associations between hearing loss and a test of their ability to retain balance.

Veterinarians: Dogs, too, can experience hearing loss
Just like humans, dogs are sometimes born with impaired hearing or experience hearing loss as a result of disease, inflammation, aging or exposure to noise.

Victorian child hearing-loss databank to go global
A unique databank that profiles children with hearing loss will help researchers globally understand why some children adapt and thrive, while others struggle.

Hearing loss, dementia risk in population of Taiwan
A population-based study using data from the National Health Insurance Research Database of Taiwan suggests hearing loss is associated with risk of dementia.

Read More: Hearing Loss News and Hearing Loss Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.