High efficient AAV-transducible transgenic quails

项目总结/摘要 这项研究计划的主要目标是产生一种转基因鹌鹑品系， 腺相关病毒（AAV）人受体。鹌鹑和鸡不能有效地转导 AAV，这排除了在这些动物中使用这类流行病毒。表达AAV受体 然而，在禽类细胞中，显著增加了AAV的转导效率。建议的第一个目标 一项研究是生产一种转基因鹌鹑品系，可以测试其内部的有效病毒转导。 耳在体内，这是目标的目标二的建议。最后的目的是证明，新的 产生的转基因AAV受体表达鹌鹑系可用于AAV介导的CRISPR-Cas9 内耳的基因组编辑。这项研究项目的成功完成将提供一种新的动物 通过体内基因操作研究禽类毛细胞再生的模型。内耳感觉毛细胞 在哺乳动物中不会自然再生，但在鸟类中会再生，这强调了引导的重要性 对鸟类进行基因改造从这个新的实验模型系统中获得的知识，例如 特定信号通路和关键基因在鸟类毛细胞再生过程中的重要性，应 可以翻译到哺乳动物，并最终可以提供洞察治疗感音神经性听力 损失

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 efficiently transduced with AAV, which precludes the use of this class of popular viruses in these animals. Expressing the AAV receptor in avian cells, however, significantly increases the transduction efficacy for AAV. The first aim of the proposed research is to generate a transgenic quail line that can be tested for efficient virus transduction of the inner ear in vivo, which is the goal of aim two of the proposal. The final 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 significance of specific 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.