MITOCHONDRIAL GENE THEREAPY IN A MACAQUE MODEL

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这项建议的主要目的是对新的生殖选择的可行性、有效性和安全性产生重要的新见解，旨在将临床相关的非人类灵长类动物模型中线粒体(MT)DNA缺陷的发生降至最低。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)卵母细胞中进行染色体转移，而不会干扰随后的核与mtDNA的相容性和发育能力。我们最近的研究证明了这种方法在恒河猴身上的可行性和有效性。我们发现，染色体移植后产生的重构卵母细胞几乎是同质的，能够支持正常受精，并能胜任猕猴婴儿的充分发育。

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.