Scientists in China have used CRISPR gene-editing technology to try treating a man with leukaemia and HIV. The study was published in The New England Journal of Medicine.

The man needed a transplant of stem cells to replace the damaged ones that were causing his blood cancer. The procedure also allowed the researchers to re-engineer a gene called CCR5 in the donor cells to be resistant to HIV. Even though the treatment didn’t control the patient’s HIV infection, the therapy appeared safe — the researchers did not detect any unintended genetic alterations, which have been a concern in the past with gene therapies. “This is an important step towards using gene editing to treat human disease,” says Fyodor Urnov, a biologist at the University of California, Berkeley. “Because of this study, we now know that these edited cells can survive in a patient, and they will stay there.”

The scientists 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. This gene-edited cells survived in the man’s 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. According to lead author Hongkui Deng, a biologist at Peking University in Beijing, the research was inspired by a remarkable bone-marrow transplant that seemingly cured a man of HIV more than a decade ago. 

The new study is very different from the unrelated, controversial case of a Chinese scientist who used CRISPR to edit the genomes of twin babies in an attempt to make them resistant to HIV. In that case, the Chinese scientist edited the DNA of embryos, and these gene alterations can be passed down to the next generation.

The work by Peking University’s Hongkui Deng and colleagues had several key differences from the earlier effort, including the controlled use of gene-editing on only select cells, the patient’s consent and the subsequent publication of the findings. In the new study, the DNA edits were made in adult cells, which cannot be passed on. 

The experiment had mixed results. Nineteen months after the treatment, the young man’s cancer, acute lymphoblastic leukaemia, is in remission, and the modified cells integrated into his body and remain. The attempt to cure his HIV was a failure with about 5% of his infection-fighting lymphocytes are now resistant to HIV, making continued treatment of the virus necessary. 

The researchers didn’t detect any adverse events from the gene-editing or signs that the man’s DNA had been damaged. Larger studies where more altered cells persist are needed to confirm the findings, Deng said. Concerns over unknown potential effects of Crispr has been one of the major hurdles standing in the way of more trials moving forward.

“This is really good news for the field,” says Carl June, an immunologist at the University of Pennsylvania in Philadelphia. “We 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.”

“This paper is an incomplete success, but it will only motivate the field to push onwards,” 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.

Source: Nature.com, The print, Livescience. 

   Send article as PDF