Until that moment, researchers had only hoped to control lumbar disease through drugs such as PrEP that reduce transmission or antiretroviral treatments that support the patient's immune system. The Berlin patient made them believe that total virus destruction was in fact possible.
His story galvanized laboratories and companies around the world to do it with the help of genetic engineering. In 2009, California-based Sangamo Therapeutics launched the first human gene editing studies to treat HIV, using an older technology called zinc-finger nucleases. These experiments, which edit a person's T cells, have yielded some limited success.
A better method, many argue, is instead to edit the cells that make T cells (and all other blood and immune cells) deep inside a person's legs. Known as hematopoietic stem cells, they tend to be more resistant to editing and require more risk and discomfort to deliver. However, if you succeed, you can provide a patient with lifetime supply of HIV immune blood and immune cells. That's what Crispr seems to offer.
The Chinese research team that conducted the latest study had previously transplanted Crispr-edited CCR5 human cells into mice, making them resistant to HIV infection. In the spring of 201
To edit the sensor stem cells, Deng's team placed them in a machine that applies a mild electrical shock. This causes the Crispr components – a DNA hacking enzyme and GPS guides that tell you where to cut it – to slide through the cell membrane and start working. This approach minimizes potential mistakes, known as off-target effects, because Crispr is only in the cells for a short period of time, which means that they are not as likely to become fake and break the DNA as they should. But it also means that not all cells are edited.
In an ideal world, both copies of the CCR5 gene would be cloned into all 163 million stem cells isolated from the donor bone marrow. It would replicate what the Berlin patient received from his donor. What the researchers got instead was much lower. After transplant, only 5.2 to 8.3 percent of the patient's bone marrow cells carried at least one copy of the CCR5 edit. (The study authors did not report how many cells that had both copies versus an edited copy.)
That number remained more or less stable over the 19 months that researchers have so far tracked the patient. But the more telling question is whether T cells in the patient's blood also retain the editing. In the specific type of T cells used by HIV to infiltrate the immune system, the broken version of CCR5 was present in only about 2 percent of them.
"It leaves a lot of room for improvement," said Paula Cannon, a molecular microbiologist who studies HIV and gene editing at the University of Southern California & # 39; s Keck School of Medicine. "At these levels, the cells cannot be expected to have much effect on the virus."
Another clinical trial, run by the City of Hope in Los Angeles, is investigating the use of zinc-finger nucleases to edit hematopoietic stem cells in HIV-positive people, with a less aggressive step in bone marrow removal, what you might call "chemo" -a little." So far, six patients have been treated, and again, after 500 days, only about 2 to 4 percent of the cells carried the mutation, according to data presented at an HIV / AIDS conference last month in Seattle.