美国研究人员不久前实现了人类卵子之间的线粒体DNA交换，并成功使这些卵子受精，由此得到的受精卵具有3个人的遗传物质。
线粒体是细胞中提供能量的细胞器，它所包含的遗传物质——线粒体DNA只通过母系遗传，即动物体内的线粒体DNA只来源于卵细胞，与精子无关。因此，母系线粒体异常会导致许多遗传病，研究人员认为更换卵子中的线粒体可望避免相关疾病。
美国俄勒冈州比弗顿市的国家灵长类动物研究中心等机构的科研人员，24日在英国期刊《自然》网站上报告说，如果一个卵子的线粒体DNA有问题，但细胞核正常，就可将其细胞核取出，然后植入另一个线粒体DNA正常并也被取出细胞核的卵子中，这样得到的卵子就可同时具有健康的细胞核及线粒体DNA。
研究人员用65个卵子进行这种实验，让交换过线粒体DNA的卵子人工受精，并将受精卵培育五六天，直至其进入囊胚期。这个阶段的受精卵已具备植入子宫的条件，但由于当前科学伦理管理的限制，本次研究中的受精卵在完成科学观察后被销毁。
2009年，这个机构的研究人员曾用同样方法交换了恒河猴卵子的线粒体DNA，随后使卵子受精，并最终产下小猴。因此，这些小猴的遗传物质分别来自两个“猴妈”和一个“猴爸”，对它们的观察尚未发现明显异常。研究人员认为，这些结果支持用同样方法可以避免人体患某类遗传疾病。
英国研究人员曾于2010年报告说培育出了交换线粒体DNA且含有3人遗传物质的人类受精卵。不过其方法是先让卵子受精，再交换受精卵的线粒体DNA，而本次研究是先交换卵子的线粒体DNA再让其受精。
英国卫生部和该国人工受精与胚胎学管理局正就这项技术的临床应用可能性进行咨询。有专家认为，现在技术已不是问题，如果能通过伦理审查并得到公众支持，可能很快就会诞生采用这种技术、携有“一父两母”遗传物质的婴儿。
Towards germline gene therapy of inherited mitochondrial diseases
Masahito Tachibana, Paula Amato, Michelle Sparman, Joy Woodward, Dario Melguizo Sanchis, Hong Ma, Nuria Marti Gutierrez, Rebecca Tippner-Hedges, Eunju Kang, Hyo-Sang Lee, Cathy Ramsey, Keith Masterson, David Battaglia, David Lee, Diana Wu, Jeffrey Jensen, Phillip Patton, Sumita Gokhale, Richard Stouffer & Shoukhrat Mitalipov
Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg’s cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle–chromosomal complex transfer). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%); however, a significant portion of ST zygotes (52%) showed abnormal fertilization as determined by an irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell isolation (38%) rates were comparable to controls. All embryonic stem cell lines derived from ST zygotes had normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing embryonic stem cells similar to controls.
文献链接：https://www.nature.com/nature/journal/vaop/ncurrent/full/nature11647.html
