1、微信公眾號(hào)：醫(yī)學(xué)博士英語南京醫(yī)科大學(xué)小白老師大閱讀第 20 天 小白老師醫(yī)學(xué)考博英語網(wǎng)絡(luò)課程Researchers get better at tweakingthe genomes of human embryosIT IS risky to predict who and what will win a Nobel prize. But some discoveriesare so big that their receipt of sciences glitziest gong seems only a matter of time.One such is CRISPR-Cas9, a

2、powerful gene-editing technique that is making thefraught and fiddly business of altering the genetic material of living organisms mucheasier.Biologists have taken to CRISPR-Cas9 with gusto, first with animal experimentsand now with tests on humans. In March researchers in China made history whenthe

3、y reported its first successful application to a disease-causing genetic mutation inhuman embryos. But their results were mixed. Although they achieved 100% successin correcting the faulty gene behind a type of anaemia called favism, they tested thetechnique in only two affected embryos. Of four oth

4、ers, carrying a mutation thatcauses thalassaemia, another anaemia, only one was successfully edited.Now, in a study just published in Nature, a group of researchers from America,China and South Korea have pulled off a similar trick, with striking consistency,among many more embryos, while avoiding o

5、r minimising several of the pitfalls ofprevious experiments. Their work suggests that, with a bit of tweaking and plenty ofelbow grease, CRISPR-Cas9 stands a good chance of graduating, sooner or later, fromthe laboratory to the clinic.The researchers involved, Hong Ma of Oregon Health & Science Univ

6、ersity andher colleagues, obtained sperm donated by a man who carries a mutated version of agene called MYBPC3 that causes hypertrophic cardiomyopathy (HCM), a condition inwhich the walls of the heart grow too thick. As with the genes that causethalassaemia and favism, inheriting even a single copy

7、of the malformed version ofthis gene is enough to cause HCM.微信公眾號(hào)：醫(yī)學(xué)博士英語南京醫(yī)科大學(xué)小白老師These sperm, half of which would havebeen carrying the mutated version ofMYBPC3, were then used to fertilise eggs containing a normal copy of the gene. Theresulting embryos thus had a 50:50 chance of containing a defec

8、tive copy. In theabsence of editing, and had they been allowed to develop, those with a faultyversion would have grown into adults likely to suffer from the disease.CRISPR-Cas9 editing has been developed from a bacterial defence system thatshreds the DNA of invading viruses. CRISPR stands for “clust

9、ered regularlyinterspaced short palindromic repeats”. These are short strings of RNA, a moleculesimilar to DNA, each designed to fix onto a particular segment of a viruss DNA. Cas9is an enzyme which, guided by CRISPRs, cuts the DNA at the specified point.Modifying this arrangement for the purposes o

10、f genetic engineering is simple, atleast in theory. Since DNA and RNA work in essentially the same ways in all livingorganisms, designing appropriately customised CRISPR guide molecules can induceCas9 to cut any cells DNA wherever the designers choose, eliminating undesirablesequences of genetic “l(fā)e

11、tters”. Since cells will then try to repair this sort of damage,genetic engineers can, by providing corrected versions of the DNA that has beendeleted for use as templates which a cell can copy, encourage the repair mechanismto fix the problem in the way they had intended.The hope was that, by being

12、 given such templates, embryos could be purged ofnascent genetic disease. That hope appeared fulfilled, at least in part. By the end ofthe experiment, 72% of the embryos were free of mutant versions of MYBPC3, animprovement on the 50% that would have escaped HCM had no editing taken place.In achievi

13、ng this, Dr Ma and her colleagues overcame two problems oftenencountered by practitioners of CRISPR-Cas9 editing. One is that the guidance systemmay go awry, with the CRISPR molecules leading the enzyme to parts of the genomethat are similar, but not quite identical, to the intended target. Happily,

14、 they foundno evidence of such off-target editing.A second problem is that, even if the edits happen in the right places, theymight not reach every cell. Many previous experiments, including some on embryos,have led to mosaicism, a condition in which the result of the editing process is an微信公眾號(hào)：醫(yī)學(xué)博士

15、英語南京醫(yī)科大學(xué)小白老師individual composed of a mixture of modified and unmodified cells. If the aim of anedit is to fix a genetic disease, such mosaicism risks nullifying the effect.Dr Ma and her colleagues conjectured that inserting the CRISPR-Cas9 moleculesinto the egg simultaneously with the sperm might he

16、lp. That way the process is givenas much time as possible to complete its work before the fertilised egg undergoes itsfirst round of cell division. Sure enough, after three days (by which time the originalfertilised egg had divided several times), all but one of the 42 embryos in which thetechnique

17、had worked showed the same modifications in every one of its cells.So far, so good. But a third problem that has bedevilled experiments withCRISPR-Cas9 concerns the quality of the repair. There are at least two ways for cellsto repair DNA damage. One of them simply stitches the severed strands of DN

18、A backtogether, deleting or adding genetic letters at random as it does so. Because itintroduces mutations of its own, this process is not suitable for correcting DNAdefects for medical purposes (though it might, for instance, be used to modify crops).Fortunately, the other mechanism patches the break with guidance from a template,and thus without introducing any additional mistakes. But cells seem to prefer theslapdash approach. In previous CRISPR-Cas9 research, the more precise method wasinvolved only 2%