Functional Auditory Genomics (Kusch)
We are interested in gene therapy for optogenetics and gene replacement therapy of various organs systems and especially the inner ear. Therefore, we use adenovirus associated virus (AAV) viral vectors for transduction of the respective target cells (sensory-, neuronal or cells of the cochlea, retina or central neuronal system and muscle cells). These “gene ferries” are non-pathogenic viral particles loaded with a gene-therapeutic DNA instead of viral DNA. Together with our colleagues in the Institute for Auditory Neuroscience, the Göttingen campus and beyond, we design, optimize and produce AAVs for research applications and pave the path towards clinical translation.
Our main questions are:
- Which AAV capsid is optimal for the cell type, species and application method planned?
- What promotor is suitable to drive transgene expression?
- How can we best pack large coding sequences into AAVs?
To target these questions, we combine molecular biology, protein biochemistry, immunohistology and optogenetics.
The development of an optical cochlea implant is an interdisciplinary effort involving multiple groups. To target spiral ganglion neurons (SGNs) of the inner ear for enabling them to respond to light, we use optimized AAV-capsids and cell-specific promotors to express desired proteins efficiently in SGNs. We analyze various combinations with different channel-rhodopsins in rodent animal models and collaborate with the Jeschke group for late preclinical tests in non-human primates.
