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Stopping HIV with an artificial protein (sciencemag.org)
88 points by adventured on Feb 18, 2015 | hide | past | web | favorite | 15 comments



This is what synthetic biology can do. Instead of taking on challenging chemistry routes to produce ever more exotic small molecules [1] which we then bathe an entire organism in, in the hopes it rubs against the HIV proteins in a way that disrupts them, synthetic biology intelligently repurposes the machinery already in place in one's body to accomplish a slightly different task. This is a primitive, if seemingly effective example.

Here, a decoy was created. It's the same set or proteins that HIV binds to in order to gain access to human cells. But the proteins are only tiny chunks from the original and are floating around on their own rather than acting as the keys to the cell. Not all that different from redirecting a heat seeking missile with a bunch of flares. But because the 'flares' are actually identical (in part) to the real proteins in a human, were HIV to mutate away from being able to bind to those chunks it too would become less virulent when attacking the real proteins. And if the strategy is effective, it takes less than a week of labwork to design and produce another similar tactic - very much unlike the small molecule variety.

[1] http://en.wikipedia.org/wiki/Tenofovir


There was an even more impressive example of synthetic biology taking on HIV treatment. The design involved re-engineering HIV to excise the retrovirus rather than integrating it into the genomes of infected cells:

https://www.youtube.com/watch?v=YgEwFVHuqUU#t=24m10s


> were HIV to mutate away from being able to bind to those chunks it too would become less virulent when attacking the real proteins.

Forgive my ignorance, but are there any indicators to predict whether a virus will evolve one way or another?

What I mean is, once it comes in contact with these mimic proteins, instead of mutating away from binding to these proteins, can it not mutate in such a way that it increases its virility so that it will bind onto more proteins in an effort to combat "false positives"? So it'll become even more virulent in individuals that have not received this treatment, and maintain its current virility in individuals receiving such treatments?


The mutations themselves are random. Generally it's reasonable to think of mutations as movement across an energetic landscape. And like in physics, nearly anything is possible if you give it enough time/energy. However, if constrained, the shortest path is usually the most likely.

Back to your question - is there an indicator to predict whether a virus will evolve towards or away from its effectiveness. Ideally, you'd put such constraints on the virus in other ways (in addition to the above concept/treatment), that it wouldn't have the energy/time to get to that much more complicated state of binding more proteins. Every additional mechanism a virus uses is a significant penalty against something as compact and efficient as a virus. But in the end there is likely no way to make any treatment perfect and unovercomable. Best we can do is defend.


Not only did they find a molecule that binds to the HIV virus like an antibody, they manipulated another virus to produce that molecule. Very impressive.

"Farzan’s team stitched the gene for eCD4-Ig into an adeno-associated virus (AAV) that is harmless to humans. Those viruses, injected into monkey muscles, continued to produce eCD4-Ig for the 40 weeks of the experiment. “Everyone expects with AAV that this can go on forever,” Farzan says."


Curiously enough, oftentimes the delivery mechanism for many of these genetic tools is the HIV scaffolding itself. It's very good at what it does - and delivering genetic payloads is one of them. Strip it entirely of its ability to be infectious and you have a very functional delivery mechanism.


I think it's safe for you to use the word "ironic" here. (There's such a backlash on the word these days that everyone is afraid to use it.)


Well, you could use any virus that uses a pre-integration complex.


Why do they need gene therapy for this? Why not produce the protein somewhere else and inject it into the animals?


Some reasons come to my mind. Continual production. Cheap. Proof of principle for gene therapy. Methodology across in vitro -> animals is identical.

Having the 'drug' produced by its host means it costs pennies to administer the first virus. It means the drug is continually produced over the time period. And frankly, it's easier than having to purify the protein from another source, figure out injection conditions/strengths, etc. Further, if it works, it's a great demonstration of gene therapy in addition to HIV treatment.


And frankly, it's easier than having to purify the protein from another source, figure out injection conditions/strengths, etc

I see where you're going, but you don't avoid a lot of that work with gene therapy. You still need to produce and the test the virus, and then scale up product along with all the purification needed. The FDA will also ask you to test various doses to provide you're giving the right amount need for the desired efficacy.

In addition, gene therapy requires additional tests to prove that the inserted genes don't end up in some weird place that causes even more issues. Not a huge cost driver, but a concern that small molecules don't have (admitting they still need carcinogenicity testing).


It's probably easier. To produce injectable amounts, they'd have to do about the same thing in a bioreactor or another animal and then extract it. Using the target as the bioreactor skips some steps--and assures a nice steady supply.


HIV transmission has been already been stopped with Truvada among high risk populations. Its weird we have coverage of studies like this that don't really note that.


From the Wikipedia article, it's not clear for me that Truvada stops completely the transmission. But the studies are more serious and the results promising that 99% of the usual overhyped drugs. http://en.wikipedia.org/wiki/Tenofovir/emtricitabine


Wikipedia isn't clear, because many gay rights organizations prefer condoms to Truvada, but there are no examples of transmission while taking Truvada daily. Serious commentators no longer debate Truvada's efficacy.




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