Could we functionally cure HIV through gene editing?

| December 3, 2015
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Charlie Sheen is far from the most sympathetic character in modern pop culture. But when he recently revealed that he was HIV positive and had been blackmailed to cover up the diagnosis for years, it was hard not to feel for the guy.

Sheen says his the virus is undetectable in his blood thanks to daily medication. Modern antiretroviral therapy is much more advanced than the early drugs available when the epidemic was first recognized. They allow patients to live decades with the virus without developing the symptoms of AIDS.  But there’s a new and potentially much more effective option. What if we could edit the HIV virus genes from our bodies?

In practice, that’s a long way off. Right now, scientists are just deciding if its ethically responsible to even test one of these gene-editing techniques in humans or using human cells. In the Petri dish however, it’s already happening. Kamel Khalili at Temple University edited the HIV virus out of several types of human cells including the immune system T-cells that are acutely infected by HIV. Quick primer on the HIV-virus. It’s a retrovirus that fits itself into the DNA of human cells. When the virus is activated it infects T-cells that protect humans from infections, leaving them immune-compromised. Using a slicing molecule made in a lab, called the CRISPR-Cas9 system, Khalili can excise, or cut out, the virus and leave healthy cells.

One concern is that the technology could go too far and chop out other regions of healthy, human DNA. But that didn’t seem to happen writes Kerry Grens at the Scientist:

One limitation of the CRISPR/Cas9 approach is that it can chop up unintended regions of the genome, producing so-called off-target effects. Khalili’s group performed whole-genome sequencing to look for off-target effects, but didn’t find any.

Other groups have used an editing technique called zinc finger nucleases to destroy the CCR5 gene in immune system cells taken from HIV positive patients. They then reintroduced those into human patients. Destroying that particular gene seemed to make the patients’ T-cells more resistant to infection. While they weren’t cured, their bodies produced more T-cells probably because destroying the CCR5 gene keep the virus from identifying or destroying them. Another group is using CRISPR to change the CCR5 gene so it includes a mutation that prevents the virus from attaching to cells.

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The success of these early technologies will, in part, lie in the outcome of a meeting being held right now in Washington D.C. where leading researchers and bioethicists are debating how CRISPR gene editing can and should be used in regards to human cells. At the heart of the question is whether we should allow the editing technology to be used for fixes that would be passed down for generations — crossing the ‘germ line.’

While that is not of concern in these therapeutic applications, it could be the case for some kinds of vaccines. By making the same changes to an embryo, everyone of its cells could carry a resistant CCR5 receptor shape, for example. That would include sperm and egg and so pass down the edited mutation. Although in theory it’s possible, that’s a less likely scenario than editing out HIV in the T-cells of a person with the virus or editing a receptor gene in the same population. But the same principal is being discussed in the very early proposals to engineer mosquitoes who would be resistant to the parasite that causes malaria. That could essentially stop the disease in human populations by giving mosquitoes a vaccine.

There is a chance that some of these gene-editing roads lead to a cure for HIV. That means patients who are positive today can rightly hope to have a cure in their lifetime, or at least the opportunity to participate in a clinical trial for one.

Meredith Knight is a contributor to the human genetics section for Genetic Literacy Project and a freelance science and health writer in Austin, Texas. Follow her @meremereknight.

The GLP featured this article to reflect the diversity of news, opinion and analysis. The viewpoint is the author’s own. The GLP’s goal is to stimulate constructive discourse on challenging science issues.

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