The treatment is considered radical, and the results were drawn from a small scale human trial, but for the first time in medical history, researchers have boosted their patients' ability to fight HIV by replacing some of their natural immune cells with genetically modified versions.
This news comes just one day after doctors announced that a second child may have been cured of HIV. This awful disease, which has killed at least 35 million people around the world, is under a full-scale assault by medical researchers. Now, in this separate study, scientists have demonstrated that GM cells can also be used to tackle the problem.
Gene editing is a form of genetic engineering where specific clips of DNA are inserted, replaced, or removed from a genome using artificially engineered zinc finger nucleases, also known as "molecular scissors." It's a process that can introduce "good" genetic mutations.
In this case, researchers from the University of Pennsylvania took advantage of a rather fortuitous and rare mutation that protects certain people from HIV. The resulting study, which now appears in the New England Journal of Medicine, is the first paper to report the modification of an exact segment of human DNA. To this point, researchers have used disabled viruses to carry and dump genes somewhat haphazardly into DNA.
The rare mutation happens in about 1% of the population and it makes them resistant to the most common strains of HIV (it's rare because both parents have to pass down the mutation for it to work). When this virus attacks a cell, it latches on to proteins that extend from the surface of the cells. But people with this mutation are deficient in a certain kind of protein — called CCR5-delta 32 — such that HIV cannot get inside their immune cells.
For the clinical trial (which began in 2009), researchers took 10 men and two women aged 31 to 54 who were all HIV positive and had been diagnosed between three and 23 years ago. As the researchers themselves admit, this is an exceptionally small sample, but it's a start. And the results were undeniably encouraging.
The first step in the process was to collect the patients' white blood cells, or T-cells. Then, using the gene editing technique, the researchers injected the rare mutation into the immune cells. These GM cells were then replicated into large batches of 10 billion and transplanted back into each patient (only around 20% were successfully modified — it's still a rather hit-and-miss process).
Prior to the procedure, all 10 patients were taking antiretroviral drugs to suppress HIV. But after being infused by the juiced-up cells, six patients were taken off their therapy in the weeks and months following (the other patients had suboptimal T cell counts despite standard drugs, so their treatment was not interrupted). Accordingly, the amount of HIV in their bodies began to rise — but as the new cells began to spread around the body, the HIV began to be suppressed.
Remarkably, one of the patients exhibited such an improvement that that HIV levels could no longer be detected; the scientists later realized that he had inherited the mutation from one parent, but not the other, effectively giving his immune system a head start.
In all, four showed improvement, while two had to be put back on their antiretrovirals (while statistically insignificant, that's a 66% success rate if you count the six, or 33% if you consider the original 12). The modified T-cells appeared to protect the patients, and could still be found in the blood several months later.
Interestingly, some of the modified cells were found to concentrate in the patients' guts — which is where HIV tends to build its stockpile. Drugs can only reduce the ability of HIV to reproduce, but it can't wipe out this reservoir.
Safe and Feasible
"This is a first — gene editing has not to date been used in a human trial [for HIV]," Bruce Levine told the BBC. "We've been able to use this technology in HIV and show it is safe and feasible, so it is an evolution in the treatment of HIV from daily antiretroviral therapy." Levine is the director of the Clinical Cell and Vaccine Production Facility at the University of Pennsylvania.
As noted, the study was done on a small scale, and the results were limited. But because of its limited success, and because it was proven safe, the study raises the hope that the gene therapy may someday replace (or at the very least supplement) the need to take daily medication. It's important to note, however, that this procedure should not be considered a cure.
So, it's now officially the dawn of the gene editing era (though it'll be a while before we see this technique used clinically). Eventually, techniques like this one could be used to treat other diseases — and without the use of drugs and their associated costs and side-effects.
Read the entire study at The New England Journal of Medicine: "Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV." Supplementary souces: The Philadelphia Inquirer, The Guardian, BBC.