Fogleman Sarah, Santana Casey, Bishop Casey, Miller Alyssa, Capco David G
Georgetown University Medical Center, Georgetown University School of Medicine Washington, D.C., USA.
School of Life Sciences, Arizona State University Tempe, AZ, USA.
Am J Stem Cells. 2016 Aug 20;5(2):39-52. eCollection 2016.
Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating mitochondrial disease: mitochondrial replacement therapy, and CRISPR/Cas9. Mitochondrial replacement therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient's nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of mitochondrial gene replacement therapy.
每年，成千上万的母亲面临将线粒体疾病遗传给后代的风险，这些疾病最严重的形式是致命的[1]。由于无法治愈，预防遗传是目前降低疾病发病率的唯一希望。目前的预防方法依赖于母体线粒体DNA突变水平较低，而那些突变水平接近或高于阈值（>60%）的母亲仍有很高的遗传风险[2]。两种新方法可能为预防和治疗线粒体疾病带来希望：线粒体替代疗法和CRISPR/Cas9。线粒体替代疗法已成为一种有前景的工具，有可能预防线粒体突变负荷较高的患者发生遗传。由于该方法使用供体胚胎移植患者的核DNA，引发了许多伦理问题；然而，它最终已在英国获批使用，并且最近美国食品药品监督管理局宣布其在伦理上是允许的。前沿的CRISPR/Cas9技术利用细菌免疫功能原理来靶向和去除突变DNA的特定序列。这可能在治疗由线粒体DNA突变引起的疾病患者方面具有潜力。随着技术的进步，本文所讨论的伦理考量变得更加突出并得以确立，这一点很重要。本综述的目的是讨论围绕这些技术的程序和疗效的当前研究，比较每种方法的伦理问题，并展望线粒体基因替代疗法的未来。
