Until that moment, scientists had only hoped to control the insidious disease through medications such as PrEP, which limit transmission, or antiretroviral treatments that strengthen patients' immune systems. The Berlin patient made her believe that complete virus destruction was indeed possible.
His story has brought labs and companies around the world to do this with genetic engineering. Californian company Sangamo Therapeutics launched its first attempts in 2009 to process human genes for the treatment of HIV with an older technology, zinc finger nucleases. These attempts to process a person's T cells have had limited success.
Many argue that a better approach is to work on the cells that make T cells (and all other blood and immune cells) deep inside a person's bones. Known as hematopoietic stem cells, they tend to be more resistant to processing and require greater risk and discomfort to be delivered. However, if you succeed, you can provide a patient with a lifetime supply of HIV-immune blood and immune cells. That seems to Crispr to offer.
The Chinese research team that carried out the most recent study had previously transplanted Crispr-edited human CCR5 mutant cells into mice, making them resistant to HIV infection. In the spring of 201
To work on the donor stem cells, Deng's team put them in a machine that exerts a slight electric shock. In this way, the Crispr components – a DNA hacking enzyme and GPS instructions that tell where to cut – can glide and work through the cell membrane. This approach minimizes potential errors called "off-target" effects because Crispr exists only for a short time in the cells. This means that they are not likely to become malignant and break the DNA they should not. It also means that not all cells are processed.
In an ideal world, both copies of the CCR5 gene would be torn into all 163 million stem cells isolated from the donor's bone marrow. That would repeat what the Berlin patient received from his donor. What the researchers got instead was much lower. After transplantation, only between 5.2 and 8.3 percent of the patient's bone marrow cells carried at least one copy of the CCR5 editor. (The authors of the study did not indicate how many cells processed both copies versus one copy.)
This number remained more or less stable during the 19 months that researchers have followed the patient. The more telling question, however, is whether T cells in the patient's blood also retain processing. In the specific type of T cells that HIV infiltrates the immune system, the defective version of CCR5 was only present in about 2 percent of them.
"That leaves a lot of room for improvement," 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, the cells are unlikely to have a strong antiviral effect." Stem cells from HIV-positive people with a less aggressive bone marrow clearing step, which could be termed "chemolites". So far, six patients have been treated and after 500 days, only about 2 to 4 percent of the cells carried the mutation, as announced at a recent HIV / AIDS conference in Seattle last month.