Reznichenko A S, Huyser C, Pepper M S
IVF Laboratory, Medfem Fertility Clinic, Bryanston, South Africa.
Department of Obstetrics and Gynaecology, University of Pretoria, Steve Biko Academic Hospital, Pretoria, South Africa.
Appl Transl Genom. 2016 Oct 15;11:40-47. doi: 10.1016/j.atg.2016.10.001. eCollection 2016 Dec.
The use of mitochondrial transfer as a clinic procedure is drawing closer to reality. Here we provide a detailed overview of mitochondrial transfer techniques - both established and recent - including pronuclear, spindle, ooplasmic and blastomere transfer. Reasons as to why some techniques are more suitable for the prevention of mitochondrial DNA disease than others, as well as the advantages and disadvantages of each methodology, are discussed. The possible clinical introduction of these techniques has raised concerns about the adverse effects they may have on resultant embryos and offspring. Success rates of each technique, embryo viability and developmental consequences post mitochondrial transfer are addressed through analysis of evidence obtained from both animal and human studies. Counterarguments against potential mitochondrial-nuclear genome incompatibility are also provided. Additional clinical applications of mitochondrial transfer techniques are discussed. These include the rescue or enhancement of fertility in women of advanced maternal age or those suffering from diabetes. An alternative to using mitochondrial DNA transfer for germ line therapies is the therapeutic use of somatic cell nuclear transfer for the generation of personalised stem cells. Although ethically challenging, this method could offer patients already suffering from mitochondrial DNA diseases a novel treatment option.
线粒体转移作为一种临床程序的应用正日益接近现实。在此,我们详细概述了线粒体转移技术——既有成熟的技术,也有最新的技术——包括原核、纺锤体、卵质和卵裂球转移。讨论了为何某些技术比其他技术更适合预防线粒体DNA疾病,以及每种方法的优缺点。这些技术可能引入临床引发了人们对其可能对所产生的胚胎和后代产生的不利影响的担忧。通过分析从动物和人体研究中获得的证据,探讨了每种技术的成功率、胚胎活力以及线粒体转移后的发育后果。还提供了针对潜在线粒体-核基因组不相容性的反驳观点。讨论了线粒体转移技术的其他临床应用。这些应用包括挽救或提高高龄产妇或患有糖尿病的女性的生育能力。用于生殖系治疗的线粒体DNA转移的一种替代方法是利用体细胞核移植治疗性生成个性化干细胞。尽管在伦理上具有挑战性,但这种方法可为已经患有线粒体DNA疾病的患者提供一种新的治疗选择。