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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 该提案的主要目标是生成有关新型生殖选择的可行性，功效和安全性的重要新见解，旨在最大程度地减少临床上相关的非人类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可以有效地被一种新颖的方法，即成熟中期II（MII）卵母细胞中的染色体转移，而不会干扰随后的Nucle-MtDNA兼容性和发育能力。我们最近的研究表明，这种方法在恒河猴中的可行性和功效。我们表明，染色体转移后产生的重建卵母细胞几乎是同质的，能够支持正常的施肥并有能力获得猕猴的完整术语发育。