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Transplanting organs brings life to the dying. But most donor organs are har
Transplanting organs brings life to the dying. But most donor organs are har
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2023-12-03
20
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问题
Transplanting 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.
One 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.
Until 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.
The 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.
Dr 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.
Dr 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.
The 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.
Since 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.
A single paper does not make a new medical procedure. 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. However, 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. [br] What does the word "swap" mean in the third paragraph?
选项
A、Exchange.
B、Insert.
C、Delete.
D、Cure.
答案
A
解析
词义题。根据上下文,swap是“交换”的意思,A为正确选项。
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