The human immunodeficiency virus, the virus that causes AIDS, usually needs the help of the human protein CCR5 to get into cells of the immune system, the T cells. About one percent of people possess a mutant form of the gene that codes for CCR5. People homozygous for this altered gene (that is, both their CCR5 genes are mutated) are able to resist infection. Even heterozygotes, people with only one mutant gene, have an advantage: their HIV infections progress to AIDS more slowly than usual.
This fascinating fact, discovered by accident more than two decades ago, has led to HIV drug therapy that blocks CCR5. Now, it appears, CCR5 may also be able to provide something entirely new: gene therapy for HIV infection. Researchers obtained T cells from the blood of each of a dozen patients and used a gene-editing technique to disrupt the CCR5 gene in the cells. The cells were then infused back into the patient they came from, thus getting around the body’s usual rejection reaction to foreign cells. The gene disruption knocked out the CCR5 gene in up to about 1 in 4 cells.
Technology Review‘s Susan Young explains what happened next: “One week after the infusion, researchers were able to find modified T cells in the patients’ blood. Four weeks after the infusion, six of the 12 patients in the study temporarily stopped taking their antiretroviral drugs so the researchers could assess the effect of the genome-editing treatment on the amount of the virus in the patients’ bodies. In four of these patients, the amount of HIV in the blood dropped. In one patient, the virus could no longer be detected at all. The team later discovered that this best responder had naturally already had one mutated copy of the CCR5 gene.”
Future studies on knocking out the CCR5 gene
This was a safety study only; there will be many more studies and regulatory hoops to jump before it’s clear whether the technique will be a useful treatment. The fact that the best responder was already a heterozygote for the CCR5 mutation has led researchers to recruit other heterozygotes for future studies. The thinking is that this gene therapy technique might work particularly well for patients who already possess protection from one mutant CCR5 gene, Sara Reardon reports at Nature News.
At Neurologica, Steven Novella says the gene therapy would be expensive, but savings on drug treatment could offset the cost. I would have thought that was a faint hope, but the New York Times says the lifetime cost of antiretroviral drugs approaches $1 million, so maybe not.
The research is not just noteworthy because it’s an attempt at gene therapy for HIV infection. It’s also the first therapeutic use of a particular gene-editing technique involving enzymes called zinc-finger nucleases(ZFN). The ZFN in this study is made by Sangamo BioSciences, a California company, and the financial stakes are serious. The study was published in the New England Journal of Medicine last Wednesday (March 5). The following day, Sangamo presented a paper at a Boston conference on retroviruses. It reported that HIV patients treated first with chemotherapy responded better to the ZFN gene therapy. Company shares rose 17% that day.
Making babies HIV-free too
At that same conference, researchers reported that the Mississippi baby treated shortly after birth with anti-HIV therapy is now 41 months old and remains HIV-free even though off therapy for nearly two years, according to Michael Smith at MedPageToday. The same tactic was tried recently on a California child born showing signs of infection, but almost all were gone within a few days. That child is still on therapy, which may be suspended at age 2. These apparent successes have prompted an international clinical trial that will study 54 babies started on anti-HIV therapy shortly after birth. It appears that even a few weeks’ delay misses the window of opportunity for forestalling infection.
According to the World Health Organization, in 2012 there were 35.3 million HIV-infected people. More than 2 million new infections occurred that year alone, and more than 1.5 million people died from AIDS-related causes. HIV infection is a particularly horrendous problem in poor places like Africa. These are places where most HIV-infected people will never have access to the most effective therapies, let alone exotic approaches like gene-editing.
So, yes, hurray for the brains and imagination and hard work that made disabling the CCR5 gene possible and holds out hope for an effective, if costly, way to block HIV infection. And hurray for all the other strategies that have, as Novella points out, turned a terrifying new fatal infection into a manageable chronic disease in just three decades.
But I can’t quite get over the tooth-grinding frustration in knowing that all this brain power and money is going into trying to fix infections that shouldn’t need fixing. Expensive gene therapy and expensive drugs shouldn’t be necessary to defeat this scourge of millions. HIV infection can be prevented. Prevented simply. Prevented cheaply. Except for the fact that so many men won’t wear condoms. Not even to save their lives.
Tabitha M. Powledge is a long-time science journalist and a contributing columnist for the Genetic Literacy Project. She writes On Science Blogs for the PLOS Blogs Network. New posts on Fridays.
- Cure for HIV? New gene-editing technique shows promise, Genetic Literacy Project
- Scientists create genetically modified cells that fight HIV, iO9
- DNA techniques show how HIV takes down the immune system, Scientist