Researchers at MIT's Lincoln Lab have developed technology that may someday cure the common cold, influenza and other ailments.
CAMBRIDGE, Mass. - August 10, 2011 - 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.
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).
Written by: Anne Trafton, MIT News Office
contact:
Marta Buczek, MIT News Office
email: mbuczek@mit.edu
phone: 617-253-2702
Source:MIT - MIT - Massachusetts Institute of Technology
http://web.mit.edu/press/2011/antiviral.html
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