10 August 2011

MIT Scientists Unleash DRACO: Viral Genocide Imminent

We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. _PLoS
PLoS One: Broad Spectrum Anti-viral

The DRACO antiviral approach created by MIT researchers has the potential to develop into an all-purpose antiviral prophylactic and early-stage treatment. This development is a timely reminder that while microbes can be shifty and clever in avoiding antimicrobial medicines, humans have incredibly creative and resourceful brains -- if they would only use them.
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.

In a paper published 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.

...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. _Physorg

So far, the treatment appears safe and non-toxic, and fairly effective when used pre-infection, and in the early stages of infection, for the viruses tested. Whether this general approach will lead to successful treatments for herpes viruses or HIV and other retroviruses, remains to be studied.

Since DRACO leads to the death of viral-infected cells, the potential exists that this approach might lead to eradication of "stealth viruses" which hide in particular cell types for a person's entire lifetime.

As for other stealth viruses living inside human cells which have not been discovered by human science, presumably some of these would also be killed by a DRACO-like approach. No one knows what the result of such a broad-spectrum clearance of body viruses might be, because no one knows what these undiscovered stealth viruses are doing in the first place. Assuming they are there, which is quite probable, according to Al Fin system biologists.

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Blogger Bearhawk said...

I'm assuming when you are talking about killing the viruses we don't know about you are also including the good ones, probiotic viral equivalents.

Also, do you think this would impact the ability to insert genetic modifications later via viral vectors?

Wednesday, 10 August, 2011  
Blogger al fin said...

DRACO actually causes viral-infected cells to commit suicide. Free viruses are not killed. But if you can kill any cells the virus infects, the infecting viruses become collateral damage.

I don't know if there are any "probiotic viral equivalents." It's possible that something analogous to bacterial probiotics could be found somewhere in a viral package, but that's speculative.

Humans already use viral vectors for gene therapies, and eventually a more wide-spectrum "probiotic virus" will almost certainly be developed.

Our genome is full of evidence that viruses have influenced our evolution for a long, long time.

So why am I reasonably certain that many of us carry around viruses in our bodies that are virtually undetectable by ordinary medical tests?

Every day we are reminded that we have uncovered only the bare "tip of the iceberg" of our world.

Stealth viruses that might at times interact with our genomes are a type of missing link, or like "a gap in the periodic table." At least that's how it seems to me. ;-)

Wednesday, 10 August, 2011  
Anonymous Anonymous said...

Although this approach has not been tested against the HIV and HTLV retroviruses, does the "dsRNA" (double stranded RNA) requirement above preclude this approach from potentially working?

Monday, 06 August, 2012  
Anonymous Anonymous said...

That's a good question - would the dsRNA (double stranded RNA) requirement above preclude this approach from potentially working against retroviruses (HTLV, HIV)?

Wednesday, 19 September, 2012  

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