Today's journal article
Bertken, Y. J., Kim, Y., Llamas, J., Beck, A., Nagiel, A., & Gnedeva, K. (2025). ShH10 viral vector for safe, efficient, and selective transduction of inner ear supporting cells.
- Developmental Biology (2025), Volume 527, Pages 289-296,
- ISSN 0012-1606,
- https://doi.org/10.1016/j.ydbio.2025.07.013.
Why I picked this article
This research project tested and developed a method of introducing genetic material to supporting cells of the cochlea.
Sensorineural hearing loss results from damage to the inner ear organ for hearing, the cochlea, and/or the auditory nerve. Approximately 1 in 1000 babies are born with sensorineural hearing loss, and approximately half of that is genetic. Recently, a gene therapy for one type of genetic hearing loss, OTOF-related genetic hearing loss (DFNB9), made huge progress in the clinical trial. The success of OTOF-gene therapy was built on the development of an effective method to introduce genes specifically to the hair cells of the cochlea, using a gene delivery cargo. These gene delivery cargoes are based on a DNA virus and are called "vector". In the case of OTOF gene therapy, AAV vectors have been very effective in delivering gene therapy to the target site within the cochlea.
This research reports a gene therapy cargo, Sh10 viral vector, to be useful in delivering gene therapy to another type of cell called "supporting cells" of the cochlea. This has the potential to push future development of gene therapies for other genetic forms of hearing loss.
Some of the research findings
Animal model:
- CD-1 mice Charles River (Strain #022)
- FVB mice Jaxon Laboratories (Strain #001800)
- Mice received viral vectors at 1-day old age (P1) -> hearing was assessed at 30- and 60-day old.
Gene therapy cassette - Viral vectors:
- AAV-ie-K558R
- AAV-DJ
- AAV2.7m8
- AAV-ShH10
How good were they on delivering genes in the cochlea? (GFP)
- AAV-ie-K558R > gene delivery in both hair cells and supporting cells.
- AAV-DJ > very little gene delivery
- AAV2.7m8 > gene delivery in both supporting cells and hair cells.
- AAV-ShH10 > gene delivery mostly in supporting cells, less in hair cells.
- *note they have also investigated utricles, and show good gene delivery.
Haruna's takeaway
AAV-ShH10 looks very promising and appears to transfect a high percentage of supporting cells. This is very positive, as some genetic hearing loss affects supporting cells first. For example, genetic hearing loss arising from GJB2 mutations will need to target supporting cells and fibrocytes. To my understanding, targeting supporting cells for gene therapy has been very challenging.
With gene therapy, the delivery of genes to the target cell type is very important for effective therapy, but it is also critical not to deliver therapy to non-target cells, as this can cause toxicity. Vectors researched in this publication are still introducing genes to hair cells in addition to supporting cells. This shows the challenge of achieving a truly cell-type-specific vector. However, specificity could also be engineered into the gene therapy itself by using the right gene promoter. So maybe we are really close to someone creating the optimal design of gene therapy for targeting supporting cells.
This is Haruna's 11/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.