MITOCHONDRIAL GENE THEREAPY IN A MACAQUE MODEL

猕猴模型中的线粒体基因治疗

• 批准号: 8357849
• 负责人: SHOUKHRAT M MITALIPOV
• 金额: $ 7.28万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357849
• 关键词: Chromosome Transfer; Competence; Defect; Development; Fertilization; Funding; Genes; Goals; Grant; Infant; Macaca; Macaca mulatta; Metaphase; Mitochondria; Mitochondrial DNA; Modeling; National Center for Research Resources; Oocytes; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Safety; Source; United States National Institutes of Health; clinically relevant; cost; design; insight; nonhuman primate; novel; novel strategies; reproductive

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The main goal of this proposal is to generate important new insights concerning feasibility, efficacy and safety of novel reproductive options designed to minimize the occurrence of mitochondrial (mt) DNA defects in a clinically relevant nonhuman primate model. Our main hypothesis is that mtDNA can be efficiently replaced by a novel approach, i.e., chromosome transfer in mature metaphase II (MII) oocytes without interfering with subsequent nucleo-mtDNA compatibility and developmental competence. Our recent studies demonstrate the feasibility and efficacy of this approach in the rhesus monkey. We showed that reconstructed oocytes produced after chromosome transfer are nearly homoplasmic, capable of supporting normal fertilization and competent for full term development of macaque infants.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该提案的主要目标是产生关于新的生殖选择的可行性，有效性和安全性的重要新见解，旨在最大限度地减少临床相关的非人灵长类动物模型中线粒体（mt）DNA缺陷的发生。我们的主要假设是mtDNA可以被一种新的方法有效地取代，即，在成熟中期II（MII）卵母细胞中的染色体转移，而不干扰随后的核-mtDNA相容性和发育能力。我们最近的研究证明了这种方法在恒河猴中的可行性和有效性。我们发现，染色体转移后产生的重构卵母细胞几乎是同质的，能够支持正常受精和猕猴婴儿的足月发育。