Read with caution!
This post was written during early stages of trying to understand a complex scientific problem, and we didn't get everything right. The original author no longer endorses the content of this post. It is being left online for historical reasons, but read at your own risk.
We’ve heard a lot lately about recent advances in gene therapy driven by the search for new vaccine-like treatments for HIV. At an MIT Enterprise Forum event earlier this month, George Church raised this as an example of the type of treatment he thinks will become more common in the future for diseases we are unable to treat with small molecule drugs.
From what I can find online it seems that there are two approaches currently being tested in humans for HIV.
One approach, described here in Science, is to disable the gene for the CCR5 receptor on T cells so that HIV is unable to attach to those cells. This involves first removing the cells from the patient’s body, mutating them and then transfusing them back in:
The trial participants had T cells removed from their blood and then modified in the laboratory with a designer enzyme engineered by Sangamo BioSciences in Richmond, California. The enzyme, called a zinc finger nuclease, clips the gene for the CCR5 receptor and disables it. Ten billion modified cells were then reinfused into the participants’ bodies, and the new data show that about 25% of cells had the mutant CCR5s.
The other approach, described in both an article and a press release in Nature, is to add a gene for an HIV antibody to a hypothetical patient’s genome by means of an adenovirus. I say hypothetical because this approach has not yet reached human trials:
We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV.
It seems both of these approaches are still a ways off from being useful for heritable prion diseases, for a couple of reasons. We’ve not yet invented an antibody that works against misfolded prion proteins, and to my knowledge we also aren’t totally certain that people can live healthily without PrP, so neither adding or deleting genes is quite an option yet. There is also the issue of drug delivery: we can’t remove neurons and astrocytes from the body in order to delete a gene, and any virus we’d inject to deliver a gene would need to be able to cross the blood-brain barrier. Still, it is heartening that gene therapy is moving along so quickly: while details remain to be worked out, this is in principle a potential treatment route for any genetic disease.