Friday, April 26, 2024
4/26/2024
Project Summary / Abstract The main goal of this research proposal is to generate a transgenic quail line that ubiquitously expresses the human receptor for adeno-associated virus (AAV). Quails and chickens cannot be e¿ciently transduced with AAV, which precludes the use of this class of popular viruses in these animals. Expressing the AAV receptor in avian cells, however, signi¿cantly increases the transduction e¿cacy for AAV. The ¿rst aim of the proposed research is to generate a transgenic quail line that can be tested for e¿cient virus transduction of the inner ear in vivo, which is the goal of aim two of the proposal. The ¿nal aim is to demonstrate that the newly generated transgenic AAV receptor-expressing quail line can be used for AAV-mediated CRISPR-Cas9 genome editing in the inner ear. The successful completion of this research project will provide a new animal model for studying avian hair cell regeneration through gene manipulation in vivo. Inner ear sensory hair cells do not naturally regenerate in mammals but they do in birds, which emphasizes the importance of conducting genetic manipulations in birds. Knowledge gained with this new experimental model system, such as the signi¿cance of speci¿c signaling pathways and key genes during avian hair cell regeneration, shall be translatable to mammals, and ultimately can provide insight into curative treatments for sensorineural hearing loss.
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