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High efficient AAV-transducible transgenic quails

高效 AAV 转导转基因鹌鹑

基本信息

批准号：
10482370
负责人：
Stefan Heller
金额：
$ 19.86万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-06 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10482370
关键词：
Animal Model Animals Basilar Papilla Biological Models Birds CRISPR/Cas technology Candidate Disease Gene Cells Chickens Clustered Regularly Interspaced Short Palindromic Repeats Cochlea Communities Coturnix Coturnix japonica Defect Dependovirus Development Embryo Epithelial Epitopes Experimental Models Future Generations Genes Genetic Goals Hair Hair Cells Human Injections Knock-out Knowledge Labyrinth MYO7A gene Mammals Mediating Mosaicism Motivation Natural regeneration Pathway interactions Proteins Quail Receptor Gene Regenerative research Research Research Personnel Research Project Grants Research Proposals Resources Sensorineural Hearing Loss Sensory Sensory Hair Serotyping Signal Pathway Structure of posterior semicircular canal Study models Supporting Cell Testing Time Transgenic Organisms Utricle structure Validation Viral Virus Virus Receptors base curative treatments enhanced green fluorescent protein experimental study genetic manipulation genome editing hair cell regeneration in vivo in vivo regeneration inner ear development insight interest knockout gene otoconia overexpression receptor tool transmission process

项目摘要

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.

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