通過基因編輯，或可治療艾滋

The 27-year-old patient's prospects were bleak. In May 2016, he found out he had AIDS. Two weeks later, he was told he had acute lymphoblastic leukemia.

這位27歲的病人前景黯淡。2016年5月，他發(fā)現(xiàn)自己患有艾滋病。兩周后，他被告知患有急性淋巴細(xì)胞白血病。

But doctors offered the Chinese citizen a ray of hope: a bone marrow transplant to treat his cancer and an extra experimental treatment to try to rid his system of HIV, according to a new paper published in The New England Journal of Medicine.

但根據(jù)《新英格蘭醫(yī)學(xué)雜志》最新發(fā)表的一篇論文，醫(yī)生們給這位中國公民帶來了一線希望：通過骨髓移植來治療他的癌癥，并進(jìn)行另外的實(shí)驗(yàn)性治療，試圖清除他體內(nèi)的艾滋病病毒。

This involved using the gene editing tool CRISPR-Cas9 to delete a gene known as CCR5 from bone marrow stem cells taken from a donor, before transplanting them into the patient, Peking University scientists said in the study.

參與研究的北京大學(xué)科學(xué)家說，治療手段包括使用基因編輯工具CRISPR-Cas9從捐贈者的骨髓干細(xì)胞中刪除一種名為CCR5的基因，然后將干細(xì)胞移植到患者體內(nèi)。

"After being edited, the cells -- and the blood cells they produce -- have the ability to resist HIV infection," lead scientist Deng Hongkui told CNN Friday.

“經(jīng)過編輯后，這些細(xì)胞——以及它們產(chǎn)生的血液細(xì)胞——有能力抵抗艾滋病毒感染，”首席科學(xué)家鄧宏魁在上周五(9月13日)告訴美國有線新聞網(wǎng)。

People who carry defective copies of CCR5 are highly immune to HIV, because the virus uses a protein made by this gene to gain entry into an infected person's cells. Two men, known as the Berlin patient and the London patient, became the first people in the world to be cured of HIV after receiving bone marrow transplants from donors who had the mutation naturally.

攜帶有發(fā)生突變的CCR5基因拷貝的人對艾滋病毒具有很高的免疫力，因?yàn)榘滩《纠眠@種基因產(chǎn)生的蛋白質(zhì)進(jìn)入感染者的細(xì)胞。“柏林患者”和“倫敦患者”在接受了來自天生攜帶有這種基因突變的捐贈者的骨髓移植后，成為世界上首批被治愈的艾滋病毒感染者。

The patient agreed and the experiment was carried out in the summer of 2017. It was the first time CRISPR-Cas9 was used on a HIV patient. In early 2019, a full 19 months after the treatment was administered, "the acute lymphoblastic leukemia was in complete remission and donor cells carrying the ablated CCR5 persisted," the scientists said in the paper.

在患者同意后，實(shí)驗(yàn)于2017年夏天進(jìn)行。這是基因編輯工具CRISPR-Cas9首次用于艾滋病毒患者。2019年初，也就是接受治療整整19個月后，“急性淋巴細(xì)胞白血病完全緩解，攜帶有經(jīng)過編輯的CCR5基因的供體細(xì)胞持續(xù)存在，”科學(xué)家在論文中說。

But there weren't enough of them to eradicate the HIV virus in the patient's body. After transplantation, only approximately 5% to 8% of the patient's bone marrow cells carried the CCR5 edit, according to the researchers. "In the future, further improving the efficiency of gene-editing and optimizing the transplantation procedure should accelerate the transition to clinical applications," said Deng.

但這還不足以消滅病人體內(nèi)的艾滋病毒。研究人員說，移植后，只有大約5%到8%的患者骨髓細(xì)胞攜帶這種經(jīng)過編輯的基因。鄧宏魁說，“在未來，進(jìn)一步提高基因編輯的效率和優(yōu)化移植程序等措施應(yīng)該會加速向臨床應(yīng)用的轉(zhuǎn)變。”

But he doesn't see this as a setback."The main purpose of the study was to evaluate the safety and feasibility of genetically-edited stem cell transplantation for AIDS treatment," said Deng.

但他不認(rèn)為這個治療是一次失敗。“這項(xiàng)研究的主要目的是評估基因編輯干細(xì)胞移植治療艾滋病的安全性和可行性，”鄧宏魁說。

According to Deng, this was a success: the scientists didn't detect any gene editing-related adverse events, even if "more long-term in-depth studies are needed for off-target effects and other safety assessments," Deng said.

他認(rèn)為這個試驗(yàn)很成功：科學(xué)家們沒有發(fā)現(xiàn)任何與基因編輯相關(guān)的不良事件，鄧宏魁說，即使“需要更長期深入的研究來進(jìn)行脫靶效應(yīng)和其他安全評估。”

The CCR5 gene mutation has been associated with a 21% increased risk of dying early, according to a paper published in Nature in June, though it's unclear why.

《自然》雜志今年6月發(fā)表的一篇論文稱，CCR5基因突變與早逝風(fēng)險(xiǎn)增加21%有關(guān)，不過原因尚不清楚。

The team that conducted the study had previously transplanted edited CCR5 human cells into mice, making them resistant to HIV. American scientists have carried out similar experiments on humans, with some success, using an older gene editing tool called zinc finger nuclease.

進(jìn)行這項(xiàng)研究的團(tuán)隊(duì)此前曾將CCR5編輯過的人類細(xì)胞移植到小鼠體內(nèi)，使其對艾滋病毒具有抵抗力。美國科學(xué)家已經(jīng)在人類身上進(jìn)行了類似的實(shí)驗(yàn)，并取得了一些成功，他們使用了一種更古老的被稱為鋅指核酸酶技術(shù)的基因編輯工具。

China has invested heavily in gene-editing technology, making biotech one the priorities of its Five-Year Plan announced in 2016. The central government has bankrolled research into a number of world "firsts," including the first use of the gene-editing tool CRISPR-Cas9 in humans in 2016 and the first reported use of gene editing technology to modify nonviable human embryos in 2015.

中國在基因編輯技術(shù)上投入巨資，將生物技術(shù)列為2016年宣布的五年規(guī)劃(十三五規(guī)劃)的重點(diǎn)之一。中國政府資助了多項(xiàng)堪稱世界“第一”的研究，包括2016年首次在人類身上使用基因編輯工具CRISPR-Cas9，以及2015年首次使用基因編輯技術(shù)修改無法存活的人類胚胎。

Deng Hongkui remains a strong believer in CRISPR-Cas9. He thinks it could "bring a new dawn" to blood-related diseases such as AIDS, sickle anemia, hemophilia and beta thalassemia and that, thanks to this new technology, "the goal of a functional cure for AIDS is getting closer and closer."

鄧宏魁仍然是基因編輯工具CRISPR-Cas9的堅(jiān)定信徒。他認(rèn)為這將為血液相關(guān)疾病帶來“新的曙光”，比如艾滋病、鐮狀細(xì)胞貧血、血友病和乙型地中海貧血。而且，由于這項(xiàng)新技術(shù)，“人們距離功能性治愈艾滋病的目標(biāo)越來越接近”。