High efficient AAV-transducible transgenic quails

高效 AAV 转导转基因鹌鹑

基本信息

批准号：
10285996
负责人：
Stefan Heller
金额：
$ 23.79万
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 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10285996
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.

项目摘要 /摘要研究建议的主要目标是生成一个无处不在表达的转基因Quair系列与腺相关病毒（AAV）的人体受体无法与之相处。 AAV，这排除了这些动物中大多数流行病毒的使用。然而，在鸟类细胞中，显着增加了AAV的转化效率。研究是生成可以对E进行测试的转基因鹌鹑线 EAR IN VIVO，这是提案的目标两个目标。生成的转基因AAV受体表达鹌鹑线可以基因组在内耳中进行了编辑。通过体内基因操纵来研究禽类细胞再生的模型。不要在哺乳动物中自然再生通过新的实验模型系统获得的鸟类的遗传操作，例如在禽毛细胞再生过程中，特定C信号通路和关键基因的显着性应为可以翻译成哺乳动物，最终可以提供有关治愈性听力的见解损失。