In 2007, a patient in Berlin underwent a high-risk bone marrow transplant to treat a dangerous but curable form of cancer called acute myeloid leukemia. After using chemotherapy and radiation to wipe out his cancerous immune cells, doctors replaced them with immune cells from a healthy individual.
While the transplant did cure his leukemia, the real reason this case is so remarkable is that it also appears to have cured the patient of HIV. HIV usually enters cells by interacting with a molecule called CCR5. However, a lucky 1% of Western Europeans have a naturally occurring mutation in both copies of this molecule that renders them essentially immune to HIV infection. His physician cleverly used cells from an individual with this mutation, and three and a half years later the so-called “Berlin patient” still seems to be free of HIV.
Unfortunately, a bone marrow transplant is not a realistic option for most of the 33 million people infected with HIV worldwide. They’re dangerous, with mortality rates up to 30%, and finding a donor with both a similar-enough immune system and an already rare mutation would be next to impossible for everyone. And, with about 10 million of these HIV-infected individuals unable to access antiretroviral drugs, such an involved and expensive procedure simply doesn’t make sense for most of the world.
So how can we transform this unique success story into a safe and affordable cure? The answer may be to make a patient’s own cells act like those from naturally immune individuals. One strategy being developed with this goal in mind is using something called a zinc finger nuclease, or ZFN, to make a patient’s own CCR5 molecules dysfunctional.
ZFNs are artificial proteins designed to act like tiny scissors: If designed specifically and directed to the right place in the body, they can seek and destroy a particular cellular component. Spurred on by the fascinating case of the Berlin patient, researchers have developed ZFNs that are able to recognize CCR5 and cut it into pieces, which would render HIV powerless against these cells.
Here’s how it would work: Doctors would draw blood from the patient and use ZFNs to modify the blood sample’s immune cells in the lab. They would then put these modified cells back into the patient, where they would divide and propagate to provide a large pool of cells resistant to infection. This fascinating strategy is now being tested in preliminary clinical trials in small numbers of HIV-infected individuals for whom antiretroviral drugs are not doing enough to stop the virus’s attack on the immune system. (Here's more details on the clinical trial, and the preliminary results.) While still in the beginning stages of research, the proof of principle provided by the Berlin patient is paving the way for ingenious strategies in the search for a cure.