![\"T-cell](\"\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-02719-w\/d41586-019-02719-w_17160300.jpg\")
<\/div>\n<\/div>HIV destroys the body’s defences by attacking immune cells.\u00a0<\/span>Credit: Steve Gschmeissner\/Science Photo Library<\/p>\n<\/figcaption><\/figure>\n <\/p>\n <\/p>\n For the first time, researchers have used CRISPR gene-editing technology to try to treat a person infected with HIV.<\/p>\n Scientists in China engineered human stem cells to mimic a rare form of natural immunity to the virus and transplanted them into a man with HIV and blood cancer. The gene-edited cells survived in the man\u2019s body for more than a year without causing detectable side effects, but the number of cells was not high enough to significantly reduce the amount of HIV in his blood.<\/p>\n \u201cThis is an important step towards using gene editing to treat human disease,\u201d says Fyodor Urnov, a biologist at the University of California, Berkeley. \u201cBecause of this study, we now know that these edited cells can survive in a patient, and they will stay there.\u201d<\/p>\n The study1<\/a><\/sup>\u00a0was published on 11 September in\u00a0The New England Journal of Medicine<\/i>. Lead author Hongkui Deng, a biologist at Peking University in Beijing, says that the research was inspired by a remarkable bone-marrow transplant that seemingly cured a man of HIV more than a decade ago.<\/p>\n <\/p>\n Mutant power<\/strong><\/p>\n In 2007, Timothy Ray Brown \u2015 initially known as \u2018the Berlin patient\u2019 \u2015 underwent a bone-marrow transplant to treat his leukaemia. The bone-marrow donor was special, however, in that he had a version of the\u00a0CCR5<\/i>\u00a0gene that confers immunity to HIV.<\/p>\n Normally, the gene encodes a receptor on the surface of white blood cells that the HIV virus uses to infiltrate cells. But in people with two copies of the\u00a0CCR5<\/i>\u00a0mutation, this receptor is warped and blocks certain strains of HIV from entering cells. The HIV-resistant version of the gene is exceptionally rare: it\u2019s found in just 1% of people of European descent, and is virtually nonexistent in other ethnic groups.<\/p>\n Doctors hoped that the bone-marrow transplant would replace Brown\u2019s HIV-susceptible blood cells with immune ones \u2014\u00a0and it did<\/a>. After nearly 13 years, there is no sign of HIV in his blood, and his leukaemia is in remission. In March, researchers reported that a\u00a0second person underwent a similar procedure in Britain and was cured<\/a>2<\/a><\/sup>.<\/p>\n Deng wanted to use CRISPR gene editing to engineer HIV-resistant blood stem cells from normal donors, making this potential cure more widely accessible. He and his colleagues tested this approach on a 27-year-old man in China who had been diagnosed with HIV and leukaemia, and who needed a bone-marrow transplant. The scientists extracted bone-marrow stem cells from a donor and used CRISPR\u2013Cas9 to transform them into\u00a0CCR5<\/i>\u00a0mutants.<\/p>\n At first, the researchers couldn\u2019t get CRISPR to knock out\u00a0CCR5<\/i>\u00a0in the stem cells. \u201cI thought, wow, these cells are really tough,\u201d says Deng. Eventually, the were able to edit 17.8% of the donor\u2019s stem cells.<\/p>\n <\/p>\n Safety first<\/strong><\/p>\n To maximize the chance that the transplant would treat the patient\u2019s cancer, the researchers mixed the edited stem cells with unedited ones. The team monitored the man after the transplant to see whether the edited cells would survive and replicate, whether they treated the HIV infection and, most importantly, whether the treatment was safe.<\/p>\n \u201cThis was the first trial, so the most important thing was to test safety,\u201d says Deng.<\/p>\n CRISPR\u00a0gene editing in people remains controversial<\/a>, in part because many researchers worry about its side effects. Studies have shown that CRISPR sometimes creates unwanted mutations in the lab3<\/a><\/sup>\u00a0\u2014 and the consequences of that happening in a person could be disastrous.<\/p>\n After 19 months, the CRISPR-edited stem cells did persist, although they comprised only 5\u20138% of the recipient\u2019s total stem cells. This means that a little over one-half of the edited cells died after they were transplanted. And although the man\u2019s leukaemia is in remission, he is still infected with HIV.<\/p>\n \u201cI\u2019m not surprised that 5% was not enough to lower the viral load,\u201d says Urnov, \u201cbut now we know that CRISPR-edited cells can persist, and that we need to do better than 5%.\u201d<\/p>\n To Deng, the most important thing is that the man did not suffer any side effects caused by the gene-edited cells. And when the researchers sequenced the genomes of those cells, they didn\u2019t find evidence of unintended genetic changes.<\/p>\n <\/p>\n Pushing forward<\/strong><\/p>\n \u201cThis is really good news for the field,\u201d says Carl June, an immunologist at the University of Pennsylvania in Philadelphia. \u201cWe now know that, in principle, we can use CRISPR to edit human stem cells, that they can persist in a patient and that it can be safe.\u201d<\/p>\n June says that this proof of concept opens the door for research into testing this technology for treatment of other blood diseases, such as sickle-cell anaemia. He also notes that this study complied with standard ethical protocols, including obtaining informed consent from the participant.<\/p>\n Improvements in gene-editing technology mean researchers can now edit stem cells with efficiency greater than the 17.8% success rate in the latest study. But that comes with risks. Each time CRISPR makes cuts in the genome, there\u2019s a chance something could go wrong. Editing cells more efficiently means making more cuts, and creates more opportunity for mistakes.<\/p>\n \u201cThis paper is an incomplete success, but it will only motivate the field to push onwards,\u201d says Urnov. Had the experiment proved to be unsafe, regulatory agencies might have stopped future research. Now, he says, researchers can point to this study as proof of concept that this line of research can be safe and potentially fruitful.<\/p>\n \u201cI\u2019m going to have an extra scoop of ice cream tonight, knowing that the ship of human genome editing for treating disease is still on course,\u201d says Urnov.<\/p>\n <\/p>\n <\/p>\n<\/div>\n <\/p>\n <\/p>\n <\/p>\n (\uc6d0\ubb38: \uc5ec\uae30<\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~)<\/p>\n <\/p>\n <\/p>\n <\/p>\n","protected":false},"excerpt":{"rendered":"