A group of researchers have designed a synthetic vector that enables safe and efficient gene transfer into the mammalian ear.
Landegger et al (2017) have designed a synthetic vector ‘Anc80L65’ for transgene delivery to the mouse cochlea.
Anc80L65 was identified out of a set of other adeno-associated viruses. Adeno-associated viruses are able to integrate into the genome of both dividing and non-dividing cells of its host. This makes it of keen interest to those interested in gene therapies (Daya and Berns 2008).
Normally inner ear hairs that allow for hearing are shaped in a V pattern (see image; Taylor et al 2012), however, a mutation (a glycine in the harmonin protein switched to an alanine) causes the hairs to lose their organisation.
Anc80L65 is able to target outer hair cells to a high degree, unlike other vectors that have been used for cochlear gene therapy. High efficiency in targeting outer hair cells is one of the main requirements for restoration of auditory function, meaning Anc80L65 may enable future gene therapies for hearing and balance disorders.
Luk Vandenberghe, one of the members of the research team, is a consultant to a number of biotech and pharmaceutical companies and is an inventor of gene therapy patents, including Anc80l65, which have been licensed to various entities. Vandenberghe is also a recipient of sponsored research from the licensees of Anc80L65.
Luk Vandenberghe, Konstantina Stankovic and Jeffrey Holt filed a patent on the use of Anc80L65 in the cochlea.
Daya, S. and Berns, K., I., 2008. Gene Therapy Using Adeno-Associated Virus Vectors. Clinical Microbiology Reviews [online], 21(4), 583-593. – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570152/
Landegger, L., D., Pan, B., Askew, C., Wassmer, S., J., Gluck, S., D., Galvin, A., Taylor, R., Forde, A., Stankovic, K., M., Holt, J., R. and Vandenberghe, L., H., 2017. A Synthetic AAV Vector Enables Safe and Efficient Gene Transfer to the Mammalian Inner Ear. Nature Biotechnology [online], 1-5. – http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3781.html
Taylor, R., R., Jagger, J., D. and Forge, A., 2012. Defining the Cellular Environment in the Organ of Corti Following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea. PLOSone [online], 7. – http://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0030577