爱思英语编者按:器官移植给垂死之人带来生命。但大多数捐献器官来自死者。志愿捐献者的数量不足,难以获得悲伤家属的同意,大多数国家致命交通事故发生率的减少(健康器官最可靠的来源),这些意味着经常缺少捐献器官。每年有成千上万的人死在等待移植的名单上。因此研究人员长期寻找增加供给的方法。

CRISPR/Cas9 gene editing
CRISPR/Cas9基因编辑

No pig in a poke
此猪非彼猪

Genome engineering may help make porcine organs suitable for use in people
基因工程能帮助猪器官适用于人

基因工程.jpg

1TRANSPLANTING organs brings life to the dying. But most donor organs are harvested from the dead. Shortfalls in the number of volunteer donors, the difficulty of gaining the consent of grieving relatives, and a reduction in most countries of the rate of fatal road accidents (the most reliable source of healthy organs), mean that there is a constant lack of them. Thousands die each year while on waiting lists for transplants. Researchers have, therefore, long sought ways to boost supply.

器官移植给垂死之人带来生命。但大多数捐献器官来自死者。志愿捐献者的数量不足,难以获得悲伤家属的同意,大多数国家致命交通事故发生率的减少(健康器官最可靠的来源),这些意味着经常缺少捐献器官。每年有成千上万的人死在等待移植的名单上。因此研究人员长期寻找增加供给的方法。

2One idea is to harvest animal organs. That is less mad than it sounds. A liver, a kidney or a cornea does the same job, regardless of species. And it works. In 1984 an American child lived for three weeks after receiving a baboon heart intended as a stopgap until a human donor could be found (unfortunately, one was not found in time). Conversely, human organs have been transplanted into animals for the purpose of research. Earlier this year, for example, a paper in the American Journal of Transplantation described moving kidneys from human fetuses into rats.

一种想法是从动物器官获取。这并没有听起来那么疯狂。肝脏,肾脏或者角膜都可以,不论什么物种。这实现了。1984年一个美国孩子,权宜之计接受了狒狒心脏后活了三周,直到找到了一个人来捐献者(不幸的是,没有及时找到)。相反的,作为研究人类器官也被移植到动物。例如今年早些时候,美国移植杂志的一篇文章描述了从人类胎儿移植肾脏到老鼠。

3Until now, though, two technical problems have stood in the way of routinely transplanting animal organs into people. One is that the recipient’s immune system must be persuaded to tolerate a big chunk of foreign tissue. The other is that swapping tissues between species risks swapping diseases, too. This second problem may soon be addressed, if George Church of the Harvard Medical School has his way. For, as he and his colleagues describe this week in Science, genetic engineering can now be used to eliminate one of the most worrying types of pathogen that might be spread via transplants.

然而直到现在,动物器官常规移植到人类的两个技术问题仍然存在。一个是接受者免疫系统必须能接受一大块外来组织。另一个是交换组织伴随产生的物种交换疾病的风险。假如哈佛医学院的乔治丘奇能成功的话,第二个问题可能不久就得到解决。像他和他的同事在本周的《Science》上描述的那样,基因工程现在能被用于消除最令人担心的一种病原体,这种病原体可能会在移植中传播。

Go the whole hog
全力以赴

4The animal most commonly suggested as a donor is the pig. Pigs are roughly the size of human beings. They are reasonably well understood. And millennia of experience mean they are easy to breed. But they are not perfect. In particular, their DNA is full of retroviruses, known specifically as porcine endogenous retroviruses, or PERVS. The genes of these viruses hitch a lift from one pig generation to another as an integral part of the porcine genome, whence they can break out and cause infection. And tests in laboratories suggest that, given the opportunity, they can infect human cells as well. The existence of PERVs, then, has been one of the main obstacles to transplanting pig organs into people.

被广泛建议用作捐赠的动物是猪。猪和人类大差不多。它们被相当地熟悉。几千年的经验表明它们容易饲养。但它们并不完美,特别是它们的DNA有逆转录酶病毒,特别是称为猪内源性逆转录病毒,PERVS。这些病毒的基因作为猪基因组不可分割部分从猪的一代搭电梯到下一代。由此它们能突变并引起感染。实验室的测试表明,只要有机会,它们也能感染人类细胞。PERVs的存在已经成为猪器官移植到人类最主要的障碍。

5Dr Church and his colleagues thought PERVs ideal candidates to test the mettle of one of the rising stars of biotechnology, CRISPR/Cas9. This is a gene-editing technique derived from bacteria, which use it as a sort of immune system. In nature, it recognises specific sequences of viral DNA and chops the DNA molecule apart at these points, protecting the bacterium from harm. Tweaked a bit in the laboratory, it can be made to recognise any DNA sequence and do likewise. This permits specific stretches of DNA to be deleted from genomes, and also allows new stretches to be inserted into the gap thus created.

丘奇博士和他的同事认为PERVs生物科技的新星理想的候选者,CRISPR/Cas9。这是一种来自细菌的基因编辑技术,是细菌用来防御的一种免疫系统。本质上,它识别特殊的病毒DNA序列,切除这些特定位点上的DNA分子,保护细菌免受伤害。在实验室微调后,它能用于识别任何DNA序列并切除。这允许特定DNA片段从基因组里删除,也能允许新的片段插入因此建立的位点空隙。

6Dr Church and his fellow researchers analysed the genetic sequences of one family of PERVs, with a view to attacking them with CRISPR/Cas9. They found that the sequence of the gene which lets the virus integrate itself into its host’s DNA is the same from one strain of virus to another. That allowed them to program a CRISPR/Cas9 system to look for this particular sequence and chop it out of the genome.

丘奇博士和他的同事分析了一种PERVs的基因序列,想到了用CRISPR/Cas9攻击他们。他们发现让病毒融入宿主DNA的基因序列,和一代传给下一代的序列是一样的。这允许他们用 CRISPR/Cas9系统来查找特定序列并将它从基因组里切除。

7The porcine kidney cells Dr Church used for his experiments had 62 PERVs embedded in their genomes. He and his colleagues tested their molecular scissors on several lines of these cells. In the most responsive, they managed to snip out all 62 copies of the integration gene.

丘奇博士实验用的猪肾脏有62份PERVs在它们的基因组。他和他的同事用分子剪刀在这些细胞几行测试。他们成功剪掉整合的所有62份基因。

8Since PERVs rely on this gene to infect human cells as well as porcine ones, deleting it should stop them jumping into human hosts. Sure enough, tests in Petri dishes showed that the modified pig cells did not infect human cells grown alongside them. And, despite the extensive edits made to their DNA, those pig cells seemed unharmed by the procedure.

因为PERVs依赖基因像感染猪一样来感染人类细胞,删除它应该能阻止他们跳到人类宿。足够确信这点,培养皿上的实验表明修饰过的猪细胞没能感染一起培养的人类细胞。而且,尽管对猪DNA进行大量编辑,过程中这些猪细胞似乎无恙。

基因.jpg

9A single paper does not a new medical procedure make. In particular, the editing would need to be done to sex cells,or their precursors, if actual lines of “clean” pigs were to be bred for use as organ donors. But this is still a striking result.Not only does it demonstrate that it is possible to cleanse animal cells of unwanted viral passengers, thus helping remove one of the big barriers to cross-species organ transplants; it also shows the power of a genetic-engineering technique that has existed for only three years. As the chart illustrates, the popularity of such techniques waxes and wanes. This year’s favourite can be next year’s also-ran. For now, though, CRISPR/Cas9 is on a roll.

一份简单的论文不能形成一个新的医疗项目。特别地,如果实际上“干净”的猪被饲养用于器官捐赠,这个编辑工具可能需要生殖细胞或原始生殖细胞。但这仍是一个引人注目的成果。它不仅描述了净化有非必要病毒的动物细胞是可能的,从而实现跨越了跨物种器官移植的一大障碍;它也显示了仅仅存在3年的基因工程技术的威力。正如图表所示,这种技术的普及也有阴晴圆缺。今年的热门可能是明年的冷门。但是现在CRISPR/Cas9正在走好运。

【译注】
1CRISPR/Cas9 是细菌和古细菌在长期演化过程中形成的一种适应性免疫防御,可用来对抗入侵的病毒及外源DNA。CRISPR/Cas9 系统通过将入侵噬菌体和质粒 DNA 的片段整合到 CRISPR 中,并利用相应的 CRISPR RNAs(crRNAs)来指导同源序列的降解,从而提供免疫性。

2a pig in a poke  冲动购买的东西(俗语)
中世纪的英国,有许多不法分子在繁荣的市集中行骗。卖猪的贩子,通常只会摆一只小猪在架上,当做样品让来往的客人看,其他的猪只则装在袋中,购买时一手交钱,一手交袋。通常客人购买时,都不会打开袋子检查里面的物品,而是买了就走,直到回了家,才发现里面装的原来是野猫。这句成语常和动词buy连用,若是购买装在袋子里的猪,也就是说不经过检查便“冲动的购买”。而“装在袋中的猪”便是指冲动购买的物品。