Tag Archives: Ling Lu

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.

Manipulating light at the nanoscale with kiragami-inspired technique

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At left, different patterns of slices through a thin metal foil, are made by a focused ion beam. These patterns cause the metal to fold up into predetermined shapes, which can be used for such purposes as modifying a beam of light. Courtesy of the researchers

Nanokiragami (or nano-kiragami) is a fully fledged field of research? That was news to me as was much else in a July 6, 2018 news item on ScienceDaily,

Nanokirigami has taken off as a field of research in the last few years; the approach is based on the ancient arts of origami (making 3-D shapes by folding paper) and kirigami (which allows cutting as well as folding) but applied to flat materials at the nanoscale, measured in billionths of a meter.

Now, researchers at MIT [Massachusetts Institute of Technology] and in China have for the first time applied this approach to the creation of nanodevices to manipulate light, potentially opening up new possibilities for research and, ultimately, the creation of new light-based communications, detection, or computational devices.

A July 6, 2018 MIT news release (also on EurekAlert), which originated the news item, adds detail,

The findings are described today [July 6, 2018] in the journal Science Advances, in a paper by MIT professor of mechanical engineering Nicholas X Fang and five others. Using methods based on standard microchip manufacturing technology, Fang and his team used a focused ion beam to make a precise pattern of slits in a metal foil just a few tens of nanometers thick. The process causes the foil to bend and twist itself into a complex three-dimensional shape capable of selectively filtering out light with a particular polarization.

Previous attempts to create functional kirigami devices have used more complicated fabrication methods that require a series of folding steps and have been primarily aimed at mechanical rather than optical functions, Fang says. The new nanodevices, by contrast, can be formed in a single folding step and could be used to perform a number of different optical functions.

For these initial proof-of-concept devices, the team produced a nanomechanical equivalent of specialized dichroic filters that can filter out circularly polarized light that is either “right-handed” or “left-handed.” To do so, they created a pattern just a few hundred nanometers across in the thin metal foil; the result resembles pinwheel blades, with a twist in one direction that selects the corresponding twist of light.

The twisting and bending of the foil happens because of stresses introduced by the same ion beam that slices through the metal. When using ion beams with low dosages, many vacancies are created, and some of the ions end up lodged in the crystal lattice of the metal, pushing the lattice out of shape and creating strong stresses that induce the bending.

“We cut the material with an ion beam instead of scissors, by writing the focused ion beam across this metal sheet with a prescribed pattern,” Fang says. “So you end up with this metal ribbon that is wrinkling up” in the precisely planned pattern.

“It’s a very nice connection of the two fields, mechanics and optics,” Fang says. The team used helical patterns to separate out the clockwise and counterclockwise polarized portions of a light beam, which may represent “a brand new direction” for nanokirigami research, he says.

The technique is straightforward enough that, with the equations the team developed, researchers should now be able to calculate backward from a desired set of optical characteristics and produce the needed pattern of slits and folds to produce just that effect, Fang says.

“It allows a prediction based on optical functionalities” to create patterns that achieve the desired result, he adds. “Previously, people were always trying to cut by intuition” to create kirigami patterns for a particular desired outcome.

The research is still at an early stage, Fang points out, so more research will be needed on possible applications. But these devices are orders of magnitude smaller than conventional counterparts that perform the same optical functions, so these advances could lead to more complex optical chips for sensing, computation, or communications systems or biomedical devices, the team says.

For example, Fang says, devices to measure glucose levels often use measurements of light polarity, because glucose molecules exist in both right- and left-handed forms which interact differently with light. “When you pass light through the solution, you can see the concentration of one version of the molecule, as opposed to the mixture of both,” Fang explains, and this method could allow for much smaller, more efficient detectors.

Circular polarization is also a method used to allow multiple laser beams to travel through a fiber-optic cable without interfering with each other. “People have been looking for such a system for laser optical communications systems” to separate the beams in devices called optical isolaters, Fang says. “We have shown that it’s possible to make them in nanometer sizes.”

The team also included MIT graduate student Huifeng Du; Zhiguang Liu, Jiafang Li (project supervisor), and Ling Lu at the Chinese Academy of Sciences in Beijing; and Zhi-Yuan Li at the South China University of Technology. The work was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and the U.S Air Force Office of Scientific Research.

The researchers have also provided some GIFs,

And,

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

Nano-kirigami with giant optical chirality by Zhiguang Liu, Huifeng Du, Jiafang Li, Ling Lu, Zhi-Yuan Li, and Nicholas X. Fang. Science Advances 06 Jul 2018: Vol. 4, no. 7, eaat4436 DOI: 10.1126/sciadv.aat4436

This paper is open access.