[Project 2501]

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Most bacterial infections can be treated with antibiotics such as penicillin, discovered decades ago. However, such drugs are useless against viral infections, including influenza, the common cold, and deadly hemorrhagic fevers such as Ebola.

Now, in a development that could transform how viral infections are treated, a team of researchers at MIT’s Lincoln Laboratory has designed a drug that can identify cells that have been infected by any type of virus, then kill those cells to terminate the infection.


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The microscope images above show that DRACO successfully treats viral infections. In the left set of four photos, rhinovirus (the common cold virus) kills untreated human cells (lower left), whereas DRACO has no toxicity in uninfected cells (upper right) and cures an infected cell population (lower right). Similarly, in the right set of four photos, dengue hemorrhagic fever virus kills untreated monkey cells (lower left), whereas DRACO has no toxicity in uninfected cells (upper right) and cures an infected cell population (lower right).


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July 27 in the journal PLoS One, the researchers tested their drug against 15 viruses, and found it was effective against all of them — including rhinoviruses that cause the common cold, H1N1 influenza, a stomach virus, a polio virus, dengue fever and several other types of hemorrhagic fever.

The drug works by targeting a type of RNA produced only in cells that have been infected by viruses. “In theory, it should work against all viruses,” says Todd Rider, a senior staff scientist in Lincoln Laboratory’s Chemical, Biological, and Nanoscale Technologies Group who invented the new technology.

Because the technology is so broad-spectrum, it could potentially also be used to combat outbreaks of new viruses, such as the 2003 SARS (severe acute respiratory syndrome) outbreak, Rider says.

Other members of the research team are Lincoln Lab staff members Scott Wick, Christina Zook, Tara Boettcher, Jennifer Pancoast and Benjamin Zusman.

Few antivirals available

Rider had the idea to try developing a broad-spectrum antiviral therapy about 11 years ago, after inventing CANARY (Cellular Analysis and Notification of Antigen Risks and Yields), a biosensor that can rapidly identify pathogens. “If you detect a pathogenic bacterium in the environment, there is probably an antibiotic that could be used to treat someone exposed to that, but I realized there are very few treatments out there for viruses,” he says.

There are a handful of drugs that combat specific viruses, such as the protease inhibitors used to control HIV infection, but these are relatively few in number and susceptible to viral resistance.

Rider drew inspiration for his therapeutic agents, dubbed DRACOs (Double-stranded RNA Activated Caspase Oligomerizers), from living cells’ own defense systems.

When viruses infect a cell, they take over its cellular machinery for their own purpose — that is, creating more copies of the virus. During this process, the viruses create long strings of double-stranded RNA (dsRNA), which is not found in human or other animal cells.

As part of their natural defenses against viral infection, human cells have proteins that latch onto dsRNA, setting off a cascade of reactions that prevents the virus from replicating itself. However, many viruses can outsmart that system by blocking one of the steps further down the cascade.

Rider had the idea to combine a dsRNA-binding protein with another protein that induces cells to undergo apoptosis (programmed cell suicide) — launched, for example, when a cell determines it is en route to becoming cancerous. Therefore, when one end of the DRACO binds to dsRNA, it signals the other end of the DRACO to initiate cell suicide.

Combining those two elements is a “great idea” and a very novel approach, says Karla Kirkegaard, professor of microbiology and immunology at Stanford University. “Viruses are pretty good at developing resistance to things we try against them, but in this case, it’s hard to think of a simple pathway to drug resistance,” she says.

Each DRACO also includes a “delivery tag,” taken from naturally occurring proteins, that allows it to cross cell membranes and enter any human or animal cell. However, if no dsRNA is present, DRACO leaves the cell unharmed.

Most of the tests reported in this study were done in human and animal cells cultured in the lab, but the researchers also tested DRACO in mice infected with the H1N1 influenza virus. When mice were treated with DRACO, they were completely cured of the infection. The tests also showed that DRACO itself is not toxic to mice.

The researchers are now testing DRACO against more viruses in mice and beginning to get promising results. Rider says he hopes to license the technology for trials in larger animals and for eventual human clinical trials.

This work is funded by a grant from the National Institute of Allergy and Infectious Diseases and the New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, with previous funding from the Defense Advanced Research Projects Agency, Defense Threat Reduction Agency, and Director of Defense Research & Engineering (now the Assistant Secretary of Defense for Research and Engineering).

[Polymath20]

Humans will eventually control ALL the diseases!

[Mujika]

That's great...

But my concern is what happens to organs and other tissues that undergo large scale apoptosis. Especially for nervous systems cells that are infected with viruses.

And..maybe my understanding is not as clear, but what about viruses that simply lay dormant? I'm assuming at the moment that dormant viruses aren't replicating, essentially not producing dsRNA...so what would that mean about the effectiveness of DRACO? Hnmmm "if no dsRNA is present within the cell DRACO leaves the cell unharmed".

But that could mean it was ineffective fro cells with dormant viruses? Perhaps I need to go and look into viruses that lay dormant and what they actually do at all within a cell..

I am..really curious about the drug's metabolic pathway...

A delivery tag? Aren't drugs made that way? Drugs/large chemical molecules that bind to additional other elements alter the drug's ability to move from polar to non polar environments.

Just like how the phosphorylation of something like sugar in the liver is what helps it stay in the liver to be stored. Amazing how addition or subtraction of elements and their properties enable them to interact in different environments within the body.., to stay or to leave.

Also, i wonder how the drug is metabolized? Excreted? Just wonder what it does to the liver or kidneys. Just saying....though, I am even more curious about it's structure.

I wonder what the binding proetein looks like. I wonder if it is possible to just sit, look up some stuff and come up with possible ways a protein could bind to dsRNA. What is it about that protein that makes it so selective to targeting that dsRNA?

And also...once that protein is bound, how does it induce cellular death? How are those proteins bound together..how do they communicate that apoptosis needs to occur?


and....just another completely random idea but proteins are the products of their genetic components. I wound if it would be possible to create DNA/a chemical sequence that could be injected as a plasmid into RBCs that could be transfused into the patient...so that when those RBC's begin to undergo cellular division, they can generate more of that dsRNA binding protein that induces apoptosis when the cell becomes infected...

Just wondering...but this is great though. Thank you for sharing.

[Project 2501]

If it's infected it is killed by draco, I guess if you have herpes or chicken pox all those cells infected get killed, I don't know if it would be fatal or not, it's hard to say.

[Polymath20]

	Originally Posted by Project 2501 To view links or images in this forum your post count must be 2 or greater. You currently have 0 posts.
	If it's infected it is killed by draco, I guess if you have herpes or chicken pox all those cells infected get killed, I don't know if it would be fatal or not, it's hard to say.

Simply infected? Most cells in the human body have vestiges of viruses in them. I was under the impression that the virus had to be active i.e. the virus had to be actively replicating within a cell to be impacted by DRACO.

[Project 2501]

Supposedly it wipes out all cells that have been infected with a virus, as they manufacture a specific protein, draco is a smart bomb. Even if a virus is dormant in the cells the smart bomb draco will cause it to self destruct.

If I read the article correctly.

[Mujika]

I think...just reading the article does not suffice. Somehow maybe someday, I'd like to see the mechanism. I don't trust if they simply just say it destroys cells with dormant viral infection.

There's a metabolic/pathologic pathway that justifies the drug's abilities to do said things.

What if there were viruses laying dormant in some percentage of red blood cells and DRACO was introduced?
The person would undergo rapid hemolysis and excretion of cellular waste products into the rest of the vascular space. The individual could go into hypovolemic shock and die due to low blood perfusion to the heart and brain. If there is a low blood volume in that instance, you can expect the patient to have tachycardia and eventually cardiac dysrhythmias.

If draco were to attack virally infected sacral nerves and induce apoptosis, the cells would die and could cause paralysis. Collagen replaces damaged tissue but when electrical nerve impulses hit that tissue, they ricochet and can cause involuntary spasms/jerking movement of limbs. In areas such as the brain, they end up with seizures.

Huhm....which makes me wonder if the drug really can cross the blood brain barrier..

Idk, it's just important to understand the structure of the drug in order to determine/predict what it will do. Based on that, there's the issue of clinical manifestations of side effects during this drug administration and how medical staff would manage it.

The claim that this drug can theoretically cure/treat something doesn't come without a price.

---------- Post added 04-05-2012 at 09:52 PM ----------

Oh wow, there's actually a link in that article to the actual downloadable PDF file of the research study they did. K, yah i was bad and didn't click it at first.

But the article is vague to me. I guess to effectively summarize information and get it out to the public.

The actual study is 15 pages long. Has anyone tried to critically appraise this information yet? I want someone to humor me and say they know how. Actually appraising it though is going to take anywhere between 30 minutes to forever based on srs skillz.

But it'd be cool if it was actually reviewed. I do not see anything to the best of my eyesight (lol) that says it has been and in depth yet.

[envirodude]

Certainly interesting research, but something about unintended consequences is ringing in my ear, almost like it's a law...

[JGordon]

We'd better find some new earths to ship all these new people technologies like this will allow pretty quick, otherwise humanity is in for a world of hell. Intelligence lets you come up with new technologies; wisdom let's you see what they're going to do to us.

[Purgatid]

I read somewhere (and I have not verified the info) that If we multiply at the same rate as we do today, then we will have a greater mass than the universe in 6000 years. Suffice to say, nativity for the human species will inevitably have to slow down. A lot.

[Equinox]

This miracle cure sure sounds great. It could definitely solve a lot of problems. But what are the odds that it's going to be widely available in the near future at a reasonable price? Pharmaceutical corporations are interested in getting money by expending the least amount of resources. Don't you think they'd rather sell us 15 doses of something that might cure us (but might not, forcing us to buy more of it) than 1 dose of something that's virtually guaranteed to help? Even if the latter did exist, wouldn't it be cost-prohibitive (because the corporations aren't a charity)? My brother, who studies pharmaceutical chemistry as a hobby, says that even now there might be a viable cure for AIDS, but it won't be available anytime soon and certainly not at an affordable price.

[loki233]

This sounds like the beginning of a sci-fi horror movie.

[scorpiomover]

Sounds really cool. But I think that I'll wait until they've shown it works, like that it's cured everyone who gets Ebola in Africa.

	Originally Posted by Purgatid To view links or images in this forum your post count must be 2 or greater. You currently have 0 posts.
	I read somewhere (and I have not verified the info) that If we multiply at the same rate as we do today, then we will have a greater mass than the universe in 6000 years. Suffice to say, nativity for the human species will inevitably have to slow down. A lot.

If viruses and bacteria no longer slow us down, and neither does death in childbirth, either for the mother or the child, then I think we'll probably either have to cut that back to about 60 years, or have a World War every 10 years.

Joy.

[Vox]

In addition to this drug, Kary Mullis demonstrated promising results with his own cure. His method, however, holds the potential to cure both viral and bacterial infections.
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a 2009 TED video where he outlines how his method operates. In this clip, he focuses exclusively on bacterial infections, but his main
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mentions they've treated influenza using the same process.

Oddly enough, though, I haven't really heard anything about his "Altermune" idea since 2010.

[thod]

	But my concern is what happens to organs and other tissues that undergo large scale apoptosis. Especially for nervous systems cells that are infected with viruses.

Yep. You have a brain cancer the size of an orange. Well this will kill all the cancer but then what? Do the dead cells get flushed out. Are you going to be left with a hole in your brain that lets everything rattle around?

[Nightmare]

Even if this is legitimate, the FDA will never approve this for use. Less people sick = less hospital visits = less revenue. That, or they will jack the price up to make it impossible to pay for... Of course, assuming this will even get off the ground.

[themuzicman]

All your disease are belong to us!

I want a new drug!

[Polymath20]

	Originally Posted by nightmar149 To view links or images in this forum your post count must be 2 or greater. You currently have 0 posts.
	Even if this is legitimate, the FDA will never approve this for use. Less people sick = less hospital visits = less revenue. That, or they will jack the price up to make it impossible to pay for... Of course, assuming this will even get off the ground.

FDA doesn't profit from drug sales. The only possible way to influence whether or not this drug is legalized (assuming it is even feasible) would be to have lobbyists put pressure on Congress. Either way, if it is developed into an effective drug, and it's proven to be successful and safe in other countries, there will be enough pressure to legalize it here, I hope.

[themuzicman]

And the company who made it would profit greatly from getting it approved. The FDA can't stop a drug trial...

[Polymath20]

	Originally Posted by themuzicman To view links or images in this forum your post count must be 2 or greater. You currently have 0 posts.
	And the company who made it would profit greatly from getting it approved. The FDA can't stop a drug trial...

That's a little dicey. It depends on where the funding for the drug trial is coming from. If it's federal money, then by George, the FDA most certainly can cut it off at the knees.

However, if Merck or Glaxo, who has very deep pockets, is doing their trial, then all the FDA can do is deny any approvals - not that they would if it was proven safe and effective.

[CREB]

It has been hypothesized that, over time, pathogenic microorganisms will reach a certain stage where the evolutionary rate of their strength and specificity of host-pathogen interactions will be far outmatched by the evolutionary rate of our immune system through the development of intricate and complex novel defense pathways. The evolutionary pressures provided by our evolving immune system will gradually shift host-pathogen interactions toward a more symbiotic interaction. But I think this is just pure speculation.

[HackerX]

	Originally Posted by Project 2501 To view links or images in this forum your post count must be 2 or greater. You currently have 0 posts.
	Supposedly it wipes out all cells that have been infected with a virus, as they manufacture a specific protein, draco is a smart bomb. Even if a virus is dormant in the cells the smart bomb draco will cause it to self destruct. If I read the article correctly.

Not just infected, actively replicating. The drug (as worded) detects when the virus is going through it's replication stage (that's the dsRNA bit) and goes - lol no, and causes the cell to self destruct.

It sounds scarier than it really is.

I don't get the whole paranoia about the drug companies wanting to prevent this:
- There's still plenty of other stuff that needs fixing. Can't fix stupiditiy, so hospitals will always be needed.
- This isn't a vaccine, it's a local cure.
- Productivity lost by sick people seems to be forgotten to be factored in.

[thod]

	The evolutionary pressures provided by our evolving immune system will gradually shift host-pathogen interactions toward a more symbiotic interaction.

The problem being that we have a billion year long experiment in which this has not happened.

I would be very worried about something that could kill all viruses. It would be much the same as antibiotics destroying the intestinal bacteria leading to other disease. Do viruses play an important part in our systems? Do they play a secondary role? For example killing off gut bacteria in the same way that wolves keep deer numbers under control.

[Polymath20]

Originally Posted by CREB To view links or images in this forum your post count must be 2 or greater. You currently have 0 posts.

It has been hypothesized that, over time, pathogenic microorganisms will reach a certain stage where the evolutionary rate of their strength and specificity of host-pathogen interactions will be far outmatched by the evolutionary rate of our immune system through the development of intricate and complex novel defense pathways. The evolutionary pressures provided by our evolving immune system will gradually shift host-pathogen interactions toward a more symbiotic interaction. But I think this is just pure speculation.

Over time, many viruses become "absorbed" into the host genome. The only way to neutralize some of those ancient viruses was to build them onto your DNA, and then use genetic switches to keep those virus genes turned off. It's not that the virus becomes "symbiotic" - more that the virus becomes endogenous.

Originally Posted by thod To view links or images in this forum your post count must be 2 or greater. You currently have 0 posts.

The problem being that we have a billion year long experiment in which this has not happened. I would be very worried about something that could kill all viruses. It would be much the same as antibiotics destroying the intestinal bacteria leading to other disease. Do viruses play an important part in our systems? Do they play a secondary role? For example killing off gut bacteria in the same way that wolves keep deer numbers under control.

I've never read anywhere that viruses play any sort of role in our natural flora (gut or otherwise). So far as I know, our flora is primarily bacteria and yeast (mostly candida) with perhaps a few protists. Most bacteriophages (viruses that attack bacteria rather than larger organisms) are so poorly adapted to human bodies that they only last minutes, maybe hours, before our immune systems utterly destroy them. All this leads me to believe that viruses, unlike bacteria, play a strictly detrimental role in our health.

[Lofwyr]

	Originally Posted by envirodude To view links or images in this forum your post count must be 2 or greater. You currently have 0 posts.
	Certainly interesting research, but something about unintended consequences is ringing in my ear, almost like it's a law...

Oh yeah. Cue zombie apocalypse...