Until then, scientists only hoped to control the insidious disease, through drugs such as PrEP that reduce transmission or antiretroviral treatments that strengthen the immune system of patients. The Berlin Patient made them believe that total annihilation of the virus was possible.
Its history has convinced laboratories and companies around the world to do so using genetic engineering. In 2009, Sangamo Therapeutics, based in California, launched the first human gene editing trials to treat HIV, using an older technology called zinc finger nucleases. These tests, which make it possible to edit a person's T cells, have given limited results.
In the opinion of many, a better approach is to modify the cells that form T cells (and all other blood and immune cells) deep within their bones. Known as hematopoietic stem cells, they tend to be more resistant to editing and require more risk and discomfort. But if you succeed, you can provide a patient with lifelong supply of blood and immune cells immune to HIV. That's what Crispr seems to offer.
The Chinese research team that conducted the latest study had previously transplanted Crispr-published human CRS5 mutant human cells into mice, thus making them resistant to HIV infection. In the spring of 2017, they recorded a small human trial, to be held at the 307 hospital of the Peoples Liberation Army in Beijing. Until now, researchers have recruited and treated only one patient, according to Hongkui Deng, director of the stem cell research center of Peking University and the University of Beijing. one of the co-authors of the study. But Deng expects the trial to develop once they improve the efficiency of their technique.
To modify the donor's stem cells, Deng's team placed them in a machine that applies a slight electric shock. This allows Crispr components – a DNA cutting enzyme and GPS guides indicating where to cut – to pass through the cell membrane and get to work. This approach minimizes potential errors, known as non-targeted effects, because Crispr is only present in cells for a short time, which means that they are not as likely to become malicious and break down. DNA that they are not supposed to have. But it also means that not all cells are edited.
In an ideal world, the two copies of the CCR5 gene would be found in the approximately 163 million stem cells they had isolated from the donor's bone marrow. This would duplicate what the Berlin patient has received from his donor. What the researchers had instead was much lower. After transplantation, only 5.2 to 8.3% of the patient's bone marrow cells had at least one copy of the CCR5 edit. (The authors of the study did not indicate the number of cells whose two copies had been published.)
This number remained more or less stable during the 19 months of follow-up of the patient by the researchers. But the most eloquent question is whether the T cells in the patient's blood also retain the change. In the specific type of T cells that HIV uses to infiltrate the immune system, the broken version of CCR5 was only present in about 2% of cases.
"It still leaves a lot to be done," says Paula Cannon, a molecular microbiologist who studies HIV and gene editing at the University of Southern California's Keck School of Medicine. "At these levels, cells should not have much effect against the virus."
Another clinical trial, conducted by the City of Hope in Los Angeles, is studying the use of zinc finger nucleases to alter hematopoietic stem cells of HIV-positive people, with a step of eliminating the less aggressive bone marrow, which one could call "Chimio-lite". So far, six patients have been treated and, again, after 500 days, only 2 to 4% of the cells carried the mutation, according to data presented at an HIV / AIDS conference held in Seattle last month.