我们的细胞含有线粒体，其为我们的细胞运作提供能量。这些线粒体中的每一个都含有少量的线粒体DNA。然而线粒体DNA只占整个人类基因组的0.1%且完全由母亲传给孩子。这也意味着我们的线粒体DNA的缺陷会影响线粒体的运作并导致线粒体疾病的发生。

据悉，这些严重的、往往是致命的疾病会影响到约每5000人中的1人。这些疾病是不治之症，基本无法治愈。

2018年，剑桥大学MRC线粒体生物学组的一个团队在小鼠身上应用了一种实验性的基因治疗方法并能成功地瞄准并消除异质细胞中受损的线粒体DNA从而使具有健康DNA的线粒体取而代之。

在最近发表在《Nature Communications》上的文章中，Michal Minczuk博士及其同事使用了一种被称为线粒体碱基编辑器的生物工具来编辑活小鼠的线粒体DNA。该治疗方法使用一种改良的病毒进入小鼠的血液中，然后被其细胞吸收。该工具会去寻找一个独特的碱基对序列--构成DNA的A、C、G和T分子的组合。原则上，这将使该工具能够纠正某些导致线粒体功能障碍的“拼写错误”。

Our cells contain mitochondria, which provide the energy for our cells to function. Each of these mitochondria contains a tiny amount of mitochondrial DNA. Mitochondrial DNA makes up only 0.1% of the overall human genome and is passed down exclusively from mother to child.

Faults in our mitochondrial DNA can affect how well the mitochondria operate, leading to mitochondrial diseases, serious and often fatal conditions that affect around 1 in 5,000 people. The diseases are incurable and largely untreatable.

In 2018, a team from the MRC Mitochondrial Biology Unit at the University of Cambridge applied an experimental gene therapy treatment in mice and were able to successfully target and eliminate the damaged mitochondrial DNA in heteroplasmic cells, allowing mitochondria with healthy DNA to take their place.

In their latest advance, published in Nature Communications, Dr Minczuk and colleagues used a biological tool known as a mitochondrial base editor to edit the mitochondrial DNA of live mice. The treatment is delivered into the bloodstream of the mouse using a modified virus, which is then taken up by its cells. The tool looks for a unique sequence of base pairs – combinations of the A, C, G and T molecules that make up DNA. It then changes the DNA base – in this case, changing a C to a T. This would, in principle, enable the tool to correct certain ‘spelling mistakes’ that cause the mitochondria to malfunction.