愛思英語編者按:器官移植給垂死之人帶來生命。但大多數(shù)捐獻器官來自死者。志愿捐獻者的數(shù)量不足,難以獲得悲傷家屬的同意,大多數(shù)國家致命交通事故發(fā)生率的減少(健康器官最可靠的來源),這些意味著經(jīng)常缺少捐獻器官。每年有成千上萬的人死在等待移植的名單上。因此研究人員長期尋找增加供給的方法。 CRISPR/Cas9 gene editing No pig in a poke Genome engineering may help make porcine organs suitable for use in people 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. 器官移植給垂死之人帶來生命。但大多數(shù)捐獻器官來自死者。志愿捐獻者的數(shù)量不足,難以獲得悲傷家屬的同意,大多數(shù)國家致命交通事故發(fā)生率的減少(健康器官最可靠的來源),這些意味著經(jīng)常缺少捐獻器官。每年有成千上萬的人死在等待移植的名單上。因此研究人員長期尋找增加供給的方法。 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. 一種想法是從動物器官獲取。這并沒有聽起來那么瘋狂。肝臟,腎臟或者角膜都可以,不論什么物種。這實現(xiàn)了。1984年一個美國孩子,權(quán)宜之計接受了狒狒心臟后活了三周,直到找到了一個人來捐獻者(不幸的是,沒有及時找到)。相反的,作為研究人類器官也被移植到動物。例如今年早些時候,美國移植雜志的一篇文章描述了從人類胎兒移植腎臟到老鼠。 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. 然而直到現(xiàn)在,動物器官常規(guī)移植到人類的兩個技術(shù)問題仍然存在。一個是接受者免疫系統(tǒng)必須能接受一大塊外來組織。另一個是交換組織伴隨產(chǎn)生的物種交換疾病的風險。假如哈佛醫(yī)學院的喬治丘奇能成功的話,第二個問題可能不久就得到解決。像他和他的同事在本周的《Science》上描述的那樣,基因工程現(xiàn)在能被用于消除最令人擔心的一種病原體,這種病原體可能會在移植中傳播。 Go the whole hog 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. 被廣泛建議用作捐贈的動物是豬。豬和人類大差不多。它們被相當?shù)厥煜?。幾千年的?jīng)驗表明它們?nèi)菀罪曫B(yǎng)。但它們并不完美,特別是它們的DNA有逆轉(zhuǎn)錄酶病毒,特別是稱為豬內(nèi)源性逆轉(zhuǎn)錄病毒,PERVS。這些病毒的基因作為豬基因組不可分割部分從豬的一代搭電梯到下一代。由此它們能突變并引起感染。實驗室的測試表明,只要有機會,它們也能感染人類細胞。PERVs的存在已經(jīng)成為豬器官移植到人類最主要的障礙。 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認為PERVs生物科技的新星理想的候選者,CRISPR/Cas9。這是一種來自細菌的基因編輯技術(shù),是細菌用來防御的一種免疫系統(tǒng)。本質(zhì)上,它識別特殊的病毒DNA序列,切除這些特定位點上的DNA分子,保護細菌免受傷害。在實驗室微調(diào)后,它能用于識別任何DNA序列并切除。這允許特定DNA片段從基因組里刪除,也能允許新的片段插入因此建立的位點空隙。 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種PERVs的基因序列,想到了用CRISPR/Cas9攻擊他們。他們發(fā)現(xiàn)讓病毒融入宿主DNA的基因序列,和一代傳給下一代的序列是一樣的。這允許他們用 CRISPR/Cas9系統(tǒng)來查找特定序列并將它從基因組里切除。 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. 丘奇博士實驗用的豬腎臟有62份PERVs在它們的基因組。他和他的同事用分子剪刀在這些細胞幾行測試。他們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. 因為PERVs依賴基因像感染豬一樣來感染人類細胞,刪除它應該能阻止他們跳到人類宿。足夠確信這點,培養(yǎng)皿上的實驗表明修飾過的豬細胞沒能感染一起培養(yǎng)的人類細胞。而且,盡管對豬DNA進行大量編輯,過程中這些豬細胞似乎無恙。 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. 一份簡單的論文不能形成一個新的醫(yī)療項目。特別地,如果實際上“干凈”的豬被飼養(yǎng)用于器官捐贈,這個編輯工具可能需要生殖細胞或原始生殖細胞。但這仍是一個引人注目的成果。它不僅描述了凈化有非必要病毒的動物細胞是可能的,從而實現(xiàn)跨越了跨物種器官移植的一大障礙;它也顯示了僅僅存在3年的基因工程技術(shù)的威力。正如圖表所示,這種技術(shù)的普及也有陰晴圓缺。今年的熱門可能是明年的冷門。但是現(xiàn)在CRISPR/Cas9正在走好運。 【譯注】 2a pig in a poke 沖動購買的東西(俗語) |
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