Tag Archives: Yu Sun

Single injection brings hearing back within weeks?

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This extraordinary development from Sweden’s Karolinska Institutet was announced in a July 3, 2025 news item on ScienceDaily, Note: This treatment was designed for a very specific type of genetically based deafness,

Gene therapy can improve hearing in children and adults with congenital deafness or severe hearing impairment, a new study involving researchers at Karolinska Institutet reports. Hearing improved in all ten patients, and the treatment was well-tolerated. The study was conducted in collaboration with hospitals and universities in China and is published in the journal Nature Medicine.

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The study comprised ten patients between the ages of 1 and 24 at five hospitals in China, all of whom had a genetic form of deafness or severe hearing impairment caused by mutations in a gene called OTOF. These mutations cause a deficiency of the protein otoferlin, which plays a critical part in transmitting auditory signals from the ear to the brain.

Effect within a month

The gene therapy involved using a synthetic adeno-associated virus (AAV) to deliver a functional version of the OTOF gene to the inner ear via a single injection through a membrane at the base of the cochlea called the round window.

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Best results in children

The younger patients, especially those between the ages of five and eight, responded best to the treatment. One of the participants, a seven-year-old girl, quickly recovered almost all her hearing and was able to hold daily conversations with her mother four months afterwards. However, the therapy also proved effective in adults.

“Smaller studies in China have previously shown positive results in children, but this is the first time that the method has been tested in teenagers and adults, too,” says Dr Duan. “Hearing was greatly improved in many of the participants, which can have a profound effect on their life quality. We will now be following these patients to see how lasting the effect is.”

No serious adverse reactions

The results also show that the treatment was safe and well-tolerated. The most common adverse reaction was a reduction in the number of neutrophils, a type of white blood cell. No serious adverse reactions were reported in the follow-up period of 6 to 12 months.

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A July 2, 2025 essay for The Conversation by Maoli Duan, one of the study’s authors, associate professor, and senior consultant at the Karolinska Institutet, provides more detail and context for the work, Note: Links have been removed,

Up to three in every 1,000 newborns has hearing loss in one or both ears. While cochlear implants offer remarkable hope for these children, it requires invasive surgery. These implants also cannot fully replicate the nuance of natural hearing.

But recent research my colleagues and I conducted has shown that a form of gene therapy can successfully restore hearing in toddlers and young adults born with congenital deafness.

Our research focused specifically on toddlers and young adults born with OTOF-related deafness. This condition is caused by mutations in the OTOF gene that produces the otoferlin protein –a protein critical for hearing.

The protein transmits auditory signals from the inner ear to the brain. When this gene is mutated, that transmission breaks down leading to profound hearing loss from birth.

Unlike other types of genetic deafness, people with OTOF mutations have healthy hearing structures in their inner ear – the problem is simply that one crucial gene isn’t working properly. This makes it an ideal candidate for gene therapy: if you can fix the faulty gene, the existing healthy structures should be able to restore hearing.

In our study, we used a modified virus as a delivery system to carry a working copy of the OTOF gene directly into the inner ear’s hearing cells. The virus acts like a molecular courier, delivering the genetic fix exactly where it’s needed.

The modified viruses do this by first attaching themselves to the hair cell’s surface, then convincing the cell to swallow them whole. Once inside, they hitch a ride on the cell’s natural transport system all the way to its control centre (the nucleus). There, they finally release the genetic instructions for otoferlin to the auditory neurons.

Our team had previously conducted studies in primates and young children (five- and eight-year-olds) which confirmed the virus therapy was safe. We were also able to illustrate the therapy’s potential to restore hearing – sometimes to near-normal levels.

But key questions had remained about whether the therapy could work in older patients – and what age is optimal for patients to receive the treatment.

To answer these questions, we expanded our clinical trial across five hospitals, enrolling ten participants aged one to 24 years. All were diagnosed with OTOF-related deafness. The virus therapy was injected into the inner ears of each participant.

We closely monitored safety during the 12-months of the study through ear examinations and blood tests. Hearing improvements were measured using both objective brainstem response tests and behavioural hearing assessments.

From the brainstem response tests, patients heard rapid clicking sounds or short beeps of different pitches while sensors measured the brain’s automatic electrical response. In another test, patients heard constant, steady tones at different pitches while a computer analysed brainwaves to see if they automatically followed the rhythm of these sounds.

For the behavioural hearing assessment, patients wore headphones and listened to faint beeps at different pitches. They pressed a button or raised their hand each time they heard a beep – no matter how faint.

Hearing improvements were both rapid and significant – especially in younger participants. Within the first month of treatment, the average total hearing improvement reached 62% on the objective brainstem response tests and 78% on the behavioural hearing assessments. Two participants achieved near-normal speech perception. The parent of one seven-year-old participant said her child could hear sounds just three days after treatment.

Over the 12-month study period, ten patients experienced very mild to moderate side-effects. The most common adverse effect was a decrease in white blood cells. Crucially, no serious adverse events were observed. This confirmed the favourable safety profile of this virus-based gene therapy.

Treating genetic deafness

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If you have time, Duan’s July 2, 2025 essay provides a few more details about the work and the researchers’ future plans.

Here’s a link to and a citation for the paper,

AAV gene therapy for autosomal recessive deafness 9: a single-arm trial by Jieyu Qi, Liyan Zhang, Ling Lu, Fangzhi Tan, Cheng Cheng, Yicheng Lu, Wenxiu Dong, Yinyi Zhou, Xiaolong Fu, Lulu Jiang, Chang Tan, Shanzhong Zhang, Sijie Sun, Huaien Song, Maoli Duan, Dingjun Zha, Yu Sun, Xia Gao, Lei Xu, Fan-Gang Zeng & Renjie Chai. Nature Medicine (2025) DOIhttps://doi.org/10.1038/s41591-025-03773-w: Published: 02 July 2025

This paper is behind a paywall.

Graphene fatigue

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Graphene fatigue operates under the same principle as metal fatigue. Subject graphene to stress over and over and at some point it (just like metal) will fail. Scientists at the University of Toronto (Ontatrio, Canada) and Rice University (Texas, US) have determined just how much stress graphene can withstand before breaking according to a January 28, 2020 University of Toronto news release by Tyler Irving (also on EurekAlert but published on January 29, 2020),

Graphene is a paradox. It is the thinnest material known to science, yet also one of the strongest. Now, research from University of Toronto Engineering shows that graphene is also highly resistant to fatigue — able to withstand more than a billion cycles of high stress before it breaks.

Graphene resembles a sheet of interlocking hexagonal rings, similar to the pattern you might see in bathroom flooring tiles. At each corner is a single carbon atom bonded to its three nearest neighbours. While the sheet could extend laterally over any area, it is only one atom thick.

The intrinsic strength of graphene has been measured at more than 100 gigapascals, among the highest values recorded for any material. But materials don’t always fail because the load exceeds their maximum strength. Stresses that are small but repetitive can weaken materials by causing microscopic dislocations and fractures that slowly accumulate over time, a process known as fatigue.

“To understand fatigue, imagine bending a metal spoon,” says Professor Tobin Filleter, one of the senior authors of the study, which was recently published in Nature Materials. “The first time you bend it, it just deforms. But if you keep working it back and forth, eventually it’s going to break in two.”

The research team — consisting of Filleter, fellow University of Toronto Engineering professors Chandra Veer Singh and Yu Sun, their students, and collaborators at Rice University — wanted to know how graphene would stand up to repeated stresses. Their approach included both physical experiments and computer simulations.

“In our atomistic simulations, we found that cyclic loading can lead to irreversible bond reconfigurations in the graphene lattice, causing catastrophic failure on subsequent loading,” says Singh, who along with postdoctoral fellow Sankha Mukherjee led the modelling portion of the study. “This is unusual behaviour in that while the bonds change, there are no obvious cracks or dislocations, which would usually form in metals, until the moment of failure.”

PhD candidate Teng Cui, who is co-supervised by Filleter and Sun, used the Toronto Nanofabrication Centre to build a physical device for the experiments. The design consisted of a silicon chip etched with half a million tiny holes only a few micrometres in diameter. The graphene sheet was stretched over these holes, like the head of a tiny drum.

Using an atomic force microscope, Cui then lowered a diamond-tipped probe into the hole to push on the graphene sheet, applying anywhere from 20 to 85 per cent of the force that he knew would break the material.

“We ran the cycles at a rate of 100,000 times per second,” says Cui. “Even at 70 per cent of the maximum stress, the graphene didn’t break for more than three hours, which works out to over a billion cycles. At lower stress levels, some of our trials ran for more than 17 hours.”

As with the simulations, the graphene didn’t accumulate cracks or other tell-tale signs of stress — it either broke or it didn’t.

“Unlike metals, there is no progressive damage during fatigue loading of graphene,” says Sun. “Its failure is global and catastrophic, confirming simulation results.”

The team also tested a related material, graphene oxide, which has small groups of atoms such as oxygen and hydrogen bonded to both the top and bottom of the sheet. Its fatigue behaviour was more like traditional materials, in that the failure was more progressive and localized. This suggests that the simple, regular structure of graphene is a major contributor to its unique properties.

“There are no other materials that have been studied under fatigue conditions that behave the way graphene does,” says Filleter. “We’re still working on some new theories to try and understand this.”

In terms of commercial applications, Filleter says that graphene-containing composites — mixtures of conventional plastic and graphene — are already being produced and used in sports equipment such as tennis rackets and skis.

In the future, such materials may begin to be used in cars or in aircraft, where the emphasis on light and strong materials is driven by the need to reduce weight, improve fuel efficiency and enhance environmental performance.

“There have been some studies to suggest that graphene-containing composites offer improved resistance to fatigue, but until now, nobody had measured the fatigue behaviour of the underlying material,” he says. “Our goal in doing this was to get at that fundamental understanding so that in the future, we’ll be able to design composites that work even better.”

Here’s a link to and a citation for the paper,

Fatigue of graphene by Teng Cui, Sankha Mukherjee, Parambath M. Sudeep, Guillaume Colas, Farzin Najafi, Jason Tam, Pulickel M. Ajayan, Chandra Veer Singh, Yu Sun & Tobin Filleter. Nature Materials (2020) DOI: DOIhttps://doi.org/10.1038/s41563-019-0586-y Published: 20 January 2020

This paper is behind a paywall.