Are All Viruses Bad? How Adeno-Associated Virus Is Used In Ear Gene Therapy

By: Keiziah O. Dijan | Kataegis

Would anyone willingly agree to have a virus injected into their body? Perhaps not. Because when people hear the word “virus,” it is often interpreted as something damaging, infectious, or the cause of a pandemic that brought outbreaks. Instead of causing illness, adeno-associated virus (AAV) can carry a working gene as a replacement for a faulty one, offering a potential solution for genetic conditions such as inherited deafness. But can this virus cure a disease more than just replacing a gene?

In 2012, Akil, O. et al. used mice in experimenting using recombinant AAV to deliver the Vesicular glutamate transporter 3 (Vglut3), a protein associated with the inner ear’s ability to send sound signals to the brain, successfully restoring hearing. Since then, researchers have made progress and tested gene therapy on other genes linked to inherited deafness such as Otoferlin (OTOF), Transmembrane Channel-Like Protein 1  (Tmc1), and Protocadherin-15 (Pcdh15). Using this technique, a recent study in 2025 by Jieyu Q. et al. conducted a trial in 10 participants aged 1.5 to 23.9 years who had a type of inherited deafness called autosomal recessive deafness 9 (DFNB9) which appears at birth and is severe and profound. Instead of AAV carrying Vglut3, it uses the OTOF gene.

OTOF carries the instructions to make otoferlin that helps inner hair cells of the cochlea to release chemical signals to the auditory nerve whenever sound is detected. Without OTOF, even if the ear detects a sound, the signal never reaches the brain therefore leading to loss of hearing, particularly DFNB9. But according to Akil, O. et al. even if the OTOF gene is missing, the inner ear’s hair cells and the auditory nerve cells mostly survive after birth. This suggests that the important part in detecting sound and carrying signals are still present but just can't send sound signals properly because the OTOF protein is missing. Therefore, replacing the OTOF gene could be a workable way to restore hearing. 

This is where AAV comes in. Scientists modify the virus so that it can no longer copy itself or cause disease, and instead, carries genes like OTOF. In this case, AAV carries a healthy copy of the OTOF gene and is delivered to the inner ear through a single injection into a small membrane at the base of the cochlea called the round window.

Once the AAV reaches its target, it binds to the surface of the hair cells and the cells naturally swallow the virus, a process called endocytosis. Inside the cell, the virus travels to the nucleus, which is the control center where genetic instructions are read. There, it releases the OTOF gene it carries, giving the cell the correct instructions to produce the protein otoferlin.

With these instructions, the hair cells can now make otoferlin. Once these signals reach the brain, the person can hear sounds again, restoring the sense of hearing.

This method of gene therapy showed favorable results in younger patients between 5 and 8 years old. One notable case was a 7 year old girl, who regained almost all her hearing and could have daily conversations with her mother just four months after treatment. However, it is also effective in adults with the effects being faster than younger patients. Most participants could hear  sounds within one month. By six months, all participants showed significant improvement. Moreover, their average hearing level, measured using a standard test called the pure-tone average, improved from 106 decibels, indicating severe hearing loss, to 52 decibels. Using other tests, results showed the click auditory brainstem response (ABR) threshold improved from 101 to 48 decibels, the tone-burst ABR threshold from 91 to 57 decibels, and the auditory steady-state response from 80 to 64 decibels.

More than replacing a gene, using AAV as gene therapy can indeed cure a disease. Just like how the first use of Vglut3 paved the way for using the OTOF gene, researchers are expanding to cater other common genes that also cause deafness, like GJB2 and TMC1. This breakthrough shows that viruses can be beneficial in recovering something that is once lost—hearing.