Bioengineered protein cuts HIV genome and frees cells from infection

Message boards : Rosetta@home Science : Bioengineered protein cuts HIV genome and frees cells from infection

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Profile Christoph Jansen
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Message 42852 - Posted: 29 Jun 2007, 19:56:07 UTC
Last modified: 29 Jun 2007, 19:58:00 UTC

Hi,

scientists from Dresden and Hamburg (both Germany) have created a protein that can cut the HIV genome into pieces which are thus inactivated. Infected tissue culture cells were freed from the HIV virus in that way. This is an absolute first: an HIV infection has never, not even under laboratory conditions, been successfully reversed.

Here is a short article on the topic.

To achieve this the researchers started with a recombinase from a bacteriophage and turned it into a related enzyme by forced evolution over 120 generations of intermediate stages. Recombinases are very specific enzymes that can recognise genomic sequences and cut/paste them at a defined point.

It took the scientists five years to achieve that goal - and this is where Rosetta comes into play: using Rosetta such site-specific enzymes might be designed directly in the future, and it might only take months, weeks or even days, depending on the projects growth in efficiency, accuracy and computing power. Once the correct sequence is known, a DNA strand coding the protein can be readily made using methods available.

Rosetta already now tries computing RNA structures, so it might even be possible to also compute the exact RNA or DNA target that an enzyme has to interact with once the viral genome has been sequenced. This way target and drug molecules may both be accurately modeled using the same technique. That would save a lot of additional time compared to current methods.

So, keep crunching as you see: protein design can already do a lot with traditional lab methods, but with Rosetta it might become a totally different playground in the future.

Regards,

Christoph
"I know that you believe you understand what you think I said, but I'm not sure you realize that what you heard is not what I meant." R.M. Nixon
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Message 43998 - Posted: 20 Jul 2007, 21:15:35 UTC

Nice news! Thanx for article.
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Message 44193 - Posted: 25 Jul 2007, 9:43:31 UTC

So what's the catch? Is AIDS cured once and for all?
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Message 44196 - Posted: 25 Jul 2007, 12:26:12 UTC

i would guess there are a few next steps, including making sure it doesn't cut other RNA sequences and working out how best to get it into infected cells. I guess this could be done by inserting the DNA sequence for the enzyme into the person's DNA, but I don't know much (anything) about making sure that sequence gets translated into a protein.
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Profile Christoph Jansen
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Message 44324 - Posted: 26 Jul 2007, 14:49:49 UTC - in response to Message 44193.  

So what's the catch? Is AIDS cured once and for all?


No, AIDS is of course not yet cured, as the protein used may not qualify as a drug candidate at all when tested. But the thing those researchers did with their artificial or promoted evolution is to create a protein that does a very specific task, and that is exactly what Rosetta is doing in terms of protein design. The difference being that Rosetta has the potential do it in much shorter time.

Creating proteins that cut out or disactive specific genes is one of the major goals in fighting diseases, as practically everything that is disease related in our body is finally caused or promoted by proteins. How these proteins can be administered as drugs depends on a number of things.

You can bring proteins into the body by infusions or similar if they are to be of general use, or put them on carrier substances if you want them to reach a specific target organ/cell type but do not want them to be present all the time. One example of such substances are vaccines, they are meant to create an immunity by contact with your immune system and are no longer needed after that. Another one are cancer treatments. Once the cancer is gone they are no longer needed either, maybe they are even harmful. And finally you can bring DNA strands into the body, that are inserted in cells temporarily, meaning not going into the nucleus. These strands can produce specific proteins, e.g. fighting certain viruses or bacteria, but will eventually be metabolized, i.e. decomposed, and stop producing the protein. Such a drug DNA strand can be administered like a typical medicine, just when it is needed.

And there is the possibility of inserting new genes into your genetic code permanently using special carriers. You can e.g. do that to cure hereditary diseases or acquired genetic defects, maybe also to fight diseases like AIDS, where the virus is very persistent and you may need to fight it again and again as small portions of it can reside in your body no matter how long the treatment is administered.

In all these cases current methods to identify the proteins involved and design the proteins/DNA that can address the genetic or proteomic causes are so called "wet bench" methods, that means they are extremely time and cost intensive.

But having proven that these slow and expensive methods can achieve a breakthrough in destroying the HIV virus in a cell culture only underlines the importance of Rosetta as Rosetta, once mature, gives researchers a tool to come to such results much, much quicker and more economically. In other words, they can create a lot more possible ways to eventually find that one cure for AIDS that also qualifies as a drug you can administer to humans, which is the real problem in any drug discovery process.
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Message boards : Rosetta@home Science : Bioengineered protein cuts HIV genome and frees cells from infection



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