Common Cold Cure -Todd Rider Video interview

Updated: Tuesday, 06 Sep 2011, 10:03 AM EDT
Published : Tuesday, 06 Sep 2011, 10:03 AM EDT


Kim
Carrigan

(FOX 25 / MyFoxBoston.com) - We all know it's just a matter of time until cold and flu season is upon us. Some researchers from the M.I.T. Lincoln Lab hope a new technology will soon do away with the sniffles and aches associated with a cold.

Dr. Todd Rider, a senior staff scientist in Lincoln Laboratory's chemical, biological and nanoscale technologies group at M.I.T., sat down with Kim Carrigan to discuss this possible cure for the common cold.

http://www.myfoxboston.com/dpp/morning/common-cold-cure-20110906

New Target Against Flu Virus May Extend Vaccine Potency

Antibody Uncovers Vulnerability of Protein Stem

HMS researchers have found an Achilles heel in the influenza virus that may someday make annual flu shots a thing of the past. By targeting a hidden pocket in the microbe with a newly discovered antibody, they disabled a wide range of viruses, including those that cause the avian flu and the virulent 1918 Spanish flu.

While this research could lead to clinical trials of a new antiviral as soon as 2012 and may eventually lead to a more durable influenza vaccine, its influence may extend even further. The work, described in the March Nature Structural and Molecular Biology, validates a novel approach to finding such viral vulnerabilities and reveals what may be a more general principle for defeating a variety of pathogens.

Photo by Graham Ramsay

Wayne Marasco and Jianhua Sui have discovered influenza’s Achilles heel and devised a method to attack it.

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Striking Gold
The story begins in the lab of Wayne Marasco, HMS associate professor of medicine at the Dana–Farber Cancer Institute. Twelve years ago, Marasco collected blood from 57 healthy Bostonians and used the samples to create a library of 27 billion different human antibodies.

Researchers “pan” the library by presenting it with an antigen, such as a whole virus or a protein on the viral surface. Panning unearths antibodies that bind to that antigen. Marasco used his library to isolate an antibody against SARS in 2004.
When the avian flu appeared, Marasco and first author Jianhua Sui put the library to work again. But instead of panning with the whole H5N1 influenza virus, they focused on a single protein. They isolated the H5 version of hemagglutinin, a surface protein on influenza that allows the virus to invade a cell and replicate. (The N portion is a different surface protein called neuraminidase, which allows the virus to exit the cell.) The effort uncovered 10 potential antibodies.

Sui and Marasco, in partnership with co-author Rubin Donis, chief of the molecular virology and vaccines branch of the Centers for Disease Control and Prevention, tested three of these antibodies in mice infected with a lethal dose of avian flu. The antibodies neutralized between 80 and 100 percent of the infections.

Unexpectedly, the antibodies also neutralized other strains. They knocked down H1N1 (the 1918 Spanish flu), H2N2, H6N1 and more. “It became apparent very quickly that the target they were recognizing was highly conserved,” said Marasco.

Not only were these antibodies more broadly effective than expected, they also worked differently. Most antibodies stick to the round top of the lollipop-shaped hemagglutinin protein and interfere with the protein’s ability to bind to the cell membrane. But Marasco and Sui’s antibodies were not blocking the membrane binding. “That told us right there that the antibody wasn’t working against the globular head,” said Marasco.

Stemming the flu. Each year, scientists develop new influenza vaccines to target the ever-mutating globular heads (light red) of the hemagglutinin proteins that coat the virus. A newly discovered antibody binds to the much less variable and much less accessible stem of the protein (red). Work is under way to turn this antibody into an antiviral that can be used to contain a pandemic and to protect immunosuppressed individuals during flu season. Since the machinery of the stem evolves more slowly than the head, the discovery may lead to a broadly effective influenza vaccine that lasts for longer than a single season.

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At this point, a third part of the team became critically important. Robert Liddington and his team at the Burnham Institute for Medical Research crystallized one of the antibodies bound together with hemagglutinin. “That’s when the revelations started coming,” said Marasco.

The crystal confirmed that the antibody was not bound to the enticing top of the protein, but rather to a pocket in the stem. That pocket contains complex machinery. It houses three entangled moving parts that allow the virus to infect the cell (see video). The crystal revealed that the antibody grabs onto all three and prevents that machinery from working. “In the past, people didn’t even know to look in that pocket,” said Sui.

Sui took this information and used it to search a database of more than 6,000 (and growing) known genetic variants of the flu. She found that only two versions of this complex stem-based machinery have evolved. An examination by Liddington’s team of crystal structures of known variants found the same. The antibodies Sui and Marasco found work against one version. They are now running the other version of the stem through the same panning process to find an antibody against it.

Enduring Weakness
The contrast between the slow evolution of the stem and the impossible-to-keep-up-with evolution of the head is stunning. But it is not surprising. The part of the headpiece that binds to the cell membrane is very small, said Sui. So the rest of the headpiece can change dramatically without compromising the function.

But in the stem, “the delicate and complex machinery is highly conserved,” said Donis. “The virus cannot mutate it because by doing so, it would commit suicide.” Indeed, Donis’s team attempted to force mutations in the stem, but none emerged.

In discovering this new, hidden vulnerability, the researchers have realized that the virus has been fooling them, and our bodies, all along. “The virus has very cleverly developed an area on the top of its coat protein that creates a molecular decoy,” said Marasco. He speculates that the immune system mounts a full-scale attack against the easy-to-spot decoy while it simultaneously suppresses any efforts to target the elusive stem. Similarly, new vaccines chase the decoy each season hoping to hit it just right.

DOUBLE CLICK PIC FOR VIDEO

Courtesy Dana–Farber Cancer Institute

HMS researchers are targeting a common weakness to tackle influenza.

Courtesy Dana–Farber Cancer Institute

HMS researchers are targeting a common weakness to tackle influenza.

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But now, with the new insights from this work, “a pan-therapy for all kinds of influenza may be within our grasp,” said Liddington. Further, Marasco suspects that the influenza virus’s means of protecting its most vulnerable machinery may be a more general strategy. He has observed almost the exact same system in corona viruses, such as SARS.

Assuming that approval for human testing proceeds without a hitch, the new influenza antibody will likely be used as an antiviral first. Since it is unlikely that a mutant will evolve to defeat it, the hope is that this antiviral can be stockpiled and stored for years. Marasco also speculates that it may be possible to develop a vaccine that both masks the decoy and allows the immune system to attack the less flexible stem.

In the future, Marasco plans to apply these same methods to other viruses. The team’s approach not only allows them to find novel antibodies and hidden targets, it also helps researchers respond nimbly as resistant strains evolve.

—Elizabeth Dougherty

Students may contact Wayne Marasco at wayne_marasco@dfci.harvard.edu for more information.

Conflict Disclosure: The authors report no conflicts of interest.

Funding Sources: National Institutes of Health

Source

Beyond Nano Breakthrough, MIT Team Quietly Builds Virus-Based Batteries

August 28, 2008

(Photo Courtesy of Belcher Laboratory/MIT)

CAMBRIDGE, Mass. — In a surprise power development that could have implications for electronics, cars and even the military, researchers at MIT have created the world's first batteries constructed at the nano-scale by microscopic viruses.

A much buzzed-about paper published in the Proceedings of the National Academy of Sciences earlier this month details the team's success in creating two of the three parts of a working battery—the positively charged anode and the electrolyte. But team leader Angela Belcher told PM yesterday that the team has been working seriously on cathode technology for the past year, creating several complete prototypes.

"We haven't published those yet, actually. We're just getting ready to write them up and send them off," says Belcher, who won a MacArthur "genius" grant from the for her work in 2004, and a Breakthrough Award from PM in 2006. "The cathode material has been a little more difficult, but we have several different candidates, and we have made full, working batteries."

Instead of physically arranging the component parts, researchers genetically engineer viruses to attract individual molecules of materials they're interested in, like cobalt oxide, from a solution, autonomously forming wires 17,000 times thinner than a sheet of paper that pack themselves together to form electrodes smaller than a human cell.

"Once you do the genetic engineering with the viruses themselves, you pour in the solution and they grow the right combination of these materials on them," Belcher says.

The team is working on three main architectures: Film-like structures—as small as a human cell—could form a clear film to power lab-on-a-chip applications, laminate into smart-cards, or even interface with implanted medical devices. Mesh-like architectures—billions of tiny nano-components all interfaced together—might one day replace conventional batteries in larger applications like laptops and cars. And fiber-like configurations—spun from liquid crystal like a spider's silk—might one day be woven into textiles, providing a wearable power-source for the military. "We definitely don't have full batteries on those [fiber architectures]. We've only worked on single electrodes so far, but the idea is to try to make these fiber batteries that could be integrated into textiles and woven into lots of different shapes," Belcher says.

The M13 viruses used by the team can't reproduce by themselves, and are only capable of infecting bacteria. At just 880 nanometers long—500 times smaller than a grain of salt—the bugs allow researchers to work at room temperatures and pressures with molecular precision, using and wasting fewer hazardous materials. Now that they've demonstrated that the construction of such tiny electronic components is possible, the challenge facing researchers is how to make them practical.

"What we're working on is not thinking about a particular device application, but trying to improve the quality of the anode and cathode materials—using biology just to make a higher quality material for energy density," Belcher says. "We haven't ruled out cars. That's a lot of amplification. But right now the thing is trying to make the best material possible, and if we get a really great material, then we have to think about how do you scale it." — Chris Ladd

Source

Virus Mimics Human Protein To Hijack Cell Division Machinery

ScienceDaily (May 8, 2008) — Viruses are masters of deception, duping their host's cells into helping them grow and spread. A new study has found that human cytomegalovirus (HCMV) can mimic a common regulatory protein to hijack normal cell growth machinery, disrupting a cell's primary anti-cancer mechanism.

Writing in the May 9 issue of Science, researchers from the University of Wisconsin-Madison and Harvard Medical School report that a viral protein, called UL97, masquerades as a normal regulatory enzyme to modify a tumor-suppressing protein in human cells. Unlike the normal enzyme, which can be switched on and off by the cell as needed, the viral stand-in lacks an off switch and evades cellular control. The findings represent a previously unknown way that viruses can cause uncontrolled cell growth and division.

Cells normally have tight regulatory mechanisms in place to limit multiplication to appropriate situations, such as replacing worn-out cells or repairing damage. Uncontrolled cell proliferation can lead to cancer and other disorders.

One of the most important cellular control mechanisms works through a protein called the retinoblastoma tumor suppressor protein, which slows cell growth.

"The retinoblastoma pathway is like the brakes on a car. It prevents tumor cells from growing out of control," says Robert Kalejta, an assistant professor in the UW-Madison Institute for Molecular Virology and McArdle Laboratory for Cancer Research, who led the new study. "This pathway is mutated in essentially all human cancers."

Disrupting this pathway is also advantageous for viruses. Unable to reproduce on their own, viruses rely on co-opting their host's cellular machinery, like an occupying army taking over a local factory. They are especially good at overriding or bypassing built-in control mechanisms, Kalejta says.

"Viruses are well known to encode proteins that have similar activities to cellular proteins, but they're just different enough that they're beneficial to the virus," he says. "[UL97] shares the same activities as the cellular protein, but it lacks all of the control mechanisms."

In essence, UL97 disables the brakes and hits the gas. Once a host cell is primed toward growth, HCMV takes over and steals the cell's machinery to reproduce itself.

The virus's bloodhound-like ability to seek out and target the most essential pieces of a cell's machinery makes it a valuable research tool, Kalejta says.

"Viruses are smarter than we are. They know a lot more about cells than we do, because their life depends on it - they're obligate intracellular parasites," he says. "If they attack a part of the cell - a process or a protein - you know it's important for the cell. If the virus pays attention to it, you should too."

Kalejta next hopes to use UL97 to find other proteins that may be important for cell growth. He also sees potential clinical applications down the road. HCMV infection is very common and, though it remains asymptomatic in most people, it has been implicated in some cancers and can cause trouble in people with compromised or suppressed immune systems, such as AIDS patients and transplant recipients. In addition, UL97-like proteins are also found in the other seven human herpes viruses, some of which are directly linked to cancers.

The advantages of the research are two-fold, Kalejta says. "We're studying a virus that causes human disease and might eventually find a way to treat that infection and help patients. At the same time, we're learning about how the cell works, which has implications for patients that don't have infections," he says. "You get two for the price of one."

Other authors on the paper include Adam Hume, Jonathan Finkel, and Michael Culbertson from UW-Madison and Jeremy Kamil and Donald Coen from Harvard Medical School. The work was funded by grants from the National Institutes of Health, the Wisconsin Partnership for a Healthy Future, the Burroughs Wellcome Fund, and the American Heart Association.

Adapted from materials provided by University of Wisconsin-Madison, via EurekAlert!, a service of AAAS.

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University of Wisconsin-Madison (2008, May 8). Virus Mimics Human Protein To Hijack Cell Division Machinery. ScienceDaily. Retrieved May 8, 2008, from
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Nanoengineering Artificial Lipid Envelopes Around Adenovirus by Self-Assembly

ACS Nano, 2008

ASAP Article

Digital Object Identifier: 10.1021/nn8000565

Article

Ravi Singh, Khuloud T. Al-Jamal, Lara Lacerda, and Kostas Kostarelos^*

Nanomedicine Laboratory, Centre for Drug Delivery Research, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom

^*Address correspondence to kostas.kostarelos@pharmacy.ac.uk.

ABSTRACT

We have developed a novel, reproducible, and facile methodology for the construction of artificial lipid envelopes for adenoviruses (Ad) by self-assembly of lipid molecules around the viral capsid. No alteration of the viral genome or conjugation surface chemistry at the virus capsid was necessary, therefore difficulties in production and purification associated with generating most surface-modified viruses can be eliminated. Different lipid bilayer compositions produced artificially enveloped Ad with physicochemical and biological characteristics determined by the type of lipid used. Physicochemical characteristics such as vector size, degree of aggregation, stability, and surface charge of the artificially enveloped Ad were correlated to their biological (gene transfer) function. In monolayer cell cultures, binding to the coxsackie and adenovirus receptor (CAR) was blocked using a zwitterionic envelope, whereas enhanced binding to the cell membrane was achieved using a cationic envelope. Envelopment of Ad by both zwitterionic and cationic lipid bilayers led to almost complete ablation of gene expression in cell monolayers, due to blockage of virion endosomal escape. Alternatively, artificial Ad envelopes built from lipid bilayers at the fluid phase in physiological conditions led to enhanced penetration of the vectors inside a three-dimensional tumor spheroid cell culture model and delayed gene expression in the tumor spheroid compared to nonenveloped adenovirus. These results indicate that construction of artificial envelopes for nonenveloped viruses by lipid bilayer wrapping of the viral capsids constitutes a general strategy to rationally engineer viruses at the nanoscale with control over their biological properties.

Source

Cancer Fighting Virus Study/Reolysin

by Amy Fleming
KIMT News 3 & MedStarSource

San Antonio, TX - Sarcoma is a potentially deadly form of caner attacking the soft tissues and bones.

The Natiional Cancer Institute estimates about 12,000 people are dsiagnosed with it every year and nearly 5,000 die from it.

Now there's a treatment using a virus that's showing incredible results.

The novel treatment uses a living virus called Reolysin.

It's given to the patient intravenously every day for five days, every month.

It isn't a chemotherapy drug, but it is toxic to cancer cells.

Side effects from Reolysin are extremely mild compared to traditional treatments.

For more information on the study go to www.clinicaltrials.gov. Type the identification number is the search box: NCT00503295.

You can also call The Cancer Therapy & Research Center in San Antonio, TX at 210-450-5798.

Source

Why The Flu Virus Is More Infectious In Cold Winter Temperatures

ScienceDaily (Mar. 31, 2008) — A finding by a team of scientists at the National Institutes of Health may account for why the flu virus is more infectious in cold winter temperatures than during the warmer months.

At winter temperatures, the virus’s outer covering, or envelope, hardens to a rubbery gel that could shield the virus as it passes from person to person, the researchers have found. At warmer temperatures, however, the protective gel melts to a liquid phase. But this liquid phase apparently isn’t tough enough to protect the virus against the elements, and so the virus loses its ability to spread from person to person.

“The study results open new avenues of research for thwarting winter flu outbreaks,” said National Institute of Child Health and Human Development (NICHD) Director Duane Alexander. “Now that we understand how the flu virus protects itself so that it can spread from person to person, we can work on ways to interfere with that protective mechanism.”

Influenza viruses are usually spread from person to person through coughs and sneezes. Infection with flu virus can cause mild to severe illness, and at times can lead to death.

In October of 2007, researchers working with guinea pigs showed that animals sick with the flu were more likely to get other guinea pigs sick at colder temperatures than at warmer temperatures.

In the current study, the NIH researchers used a sophisticated magnetic resonance technique, developed and previously tested in NIAAA's Laboratory of Membrane Biochemistry and Biophysics, to create a detailed fingerprint of how the virus’s outer membrane responded to variations in temperature. The virus’s outer membrane is composed chiefly of molecules known as lipids, explained the study’s senior author, Joshua Zimmerberg, Ph.D., chief of NICHD’s Laboratory of Cellular And Molecular Biophysics. This family of molecules does not mix with water, and includes oils, fats, waxes, and cholesterol.

Dr. Zimmerberg and his colleagues found that at temperatures slightly above freezing, the virus’s lipid covering solidified into a gel. As temperatures approach 60 degrees Fahrenheit, the covering gradually thaws, eventually melting to a soupy mix.

Cooler temperatures, apparently, cause the virus to form the rubbery outer covering that can withstand travel from person to person, Dr. Zimmerberg said. Once in the respiratory tract, the warm temperature in the body causes the covering to melt to its liquid form, so that the virus can infect the cells of its new host, he added.

“Like an M&M in your mouth, the protective covering melts when it enters the respiratory tract,” Dr. Zimmerberg said. “It’s only in this liquid phase that the virus is capable of entering a cell to infect it.”

In spring and summer, however, the temperatures are too high to allow the viral membrane to enter its gel state. Dr. Zimmerberg said that at these temperatures, the individual flu viruses would dry out and weaken, and this would help to account for the ending of flu season.

The finding opens up new possibilities for research, Dr. Zimmerberg said. Strategies to disrupt the virus and prevent it from spreading could involve seeking ways to disrupt the virus’s lipid membrane.

In cold temperatures, the hard lipid shell can be resistant to certain detergents, so one strategy could involve testing for more effective detergents and hand-washing protocols to hinder the spread of the virus.

Similarly, Dr. Zimmerberg added that flu researchers might wish to study whether, in areas affected by a severe form of the flu, people might better protect themselves against getting sick by remaining indoors at warmer temperatures than usual.

The findings were published online March 2 in Nature Chemical Biology. The study was a collaboration between researchers at two NIH institutes, the National Institute of Child Health and Human Development, and the National Institute on Alcohol Abuse and Alcoholism. Other authors of the paper were I.V. Polozov and L. Bezrukov, both of the Laboratory of Cellular And Molecular Biophysics at NICHD and K. Gawrisch of the Laboratory of Membrane Biochemistry and Biophysics, National Institute of Alcohol Abuse and Alcoholism. Magnetic resonance experiments were conducted and analyzed at NIAAA under Dr. Gawrisch's guidance.

Adapted from materials provided by NIH/National Institute of Child Health.

Link

Nanoparticle Chicken Feed Keeps Birds Healthy

Feb. 29, 2008 -- Researchers at Clemson University have fed nanoparticles to chickens, eliminating deadly bacteria and making the chickens safer for human consumption.

The research could reduce the number of cases of food-borne diseases in the United States and one day treat the more than five million people in developing countries who die annually from diarrhea.

"Our ultimate goal is to use these nanoparticles as a treatment for children in underdeveloped countries," said Fred Stutzenberger, a retired professor of microbiology at Clemson who is publishing a review of the research next month in the journal Advances in Applied Microbiology.

The researchers made a microscopic ball of polystyrene, the same plastic used in CD cases. Threads hang off of the ball, and at the end of each one is a molecule that, to certain bacteria, looks like sugar. E. coli, salmonella, and other potentially deadly bacteria latch onto the molecule but can't process it, and essentially glue themselves to it.

Eventually dozens of nanoparticles attach themselves to the bacteria, making it very difficult for an infection to develop or spread.

"If we can block that first interaction [between bacteria and host]," said Jeremy Tzeng, a fellow researcher and microbiologist on the project, "then we can block an infection."

With the bacteria surrounded and unable to cause an infection, they pass harmlessly through the digestive system and out of the chicken.

Nanoparticle-Fed

Since the nanoparticles latch onto an area of the cell critical for triggering an infection, it would be hard for the bacteria to develop a resistance to the nanoparticles (the same process that leads to antibiotic-resistance bacteria) and still cause an infection.

The nanoparticles are several hundred nanometers in size, too big to migrate out of the digestive system and into the rest of the bird (or, potentially, human). Separate tests done by the scientists confirmed that no nanoparticles were found in any other tissues of the chicken's body.

The nanoparticles can also be applied to the chicken feed at anytime to remove potentially deadly bacteria. For example, feeding animals the nanoparticles just before slaughter could reduce the risk of contaminating the meat with e. coli or other bacteria if a worker or machine accidentally nicks open the stomach or intestine.

They have been tested in hundreds of chickens, rabbits and mice, none of which showed any reaction to the nanoparticles.

The researchers eventually want to develop the nanoparticles to directly treat human diseases, specifically diarrheal diseases in the developing world, and have been in touch with the Bill and Melinda Gates Foundation in an effort to develop the technology.

"This is really an excellent opportunity to treat organisms without going through antibiotics," said Challa Kumar, a nanotechnology researcher at Louisiana State University who was not involved in the USDA-funded research.

"It has a tremendous commercial potential. I don't see any reason why it should fail if they try it in human beings."

LINK

I wonder if this same approach, suitably altered, would work as a viricide.

Looks like viruses are contemplated!

United States Patent Application 20070184120

Stutzenberger; Fred J. ; et al. August 9, 2007

Adhesin-specific nanoparticles and process for using same

Abstract

The present invention is generally directed to compositions useful in preventing and/or treating disease due to infection by any of a variety of biologically active pathogenic microorganisms. The compositions include nanoparticles formed of a hydrophobic polymeric core, hydrophilic linking agents bound to the core, and biofunctional materials bound to the linking agents. The biofunctional materials are functionally identical to receptors on host cell surfaces that can be recognized and bound by adhesins on the surface of the targeted pathogenic adhesin-bearing microorganisms. In one embodiment, the binding action between the nanoparticles and the microorganisms can lead to the formation of large agglomerated complexes, which can then be easily removed from an area, including the digestive tract of an infected individual. The compositions of the present invention can also be utilized in preventing enteric infections via the ability to purge animals of enteropathogens prior to transport and processing for human consumption.

Inventors: Stutzenberger; Fred J.; (Clemson, SC) ; Latour; Robert A. JR.; (Clemson, SC) ; Sun; Ya-Ping; (Clemson, SC) ; Tzeng; Tzuen R.; (US)

Assignee Name and Adress: Clemson University

Serial No.: 677132
Series Code: 10
Filed: October 1, 2003

Claims

1. A composition capable of binding to a biologically active microorganism comprising: a nanoparticle, said nanoparticle comprising a hydrophobic polymeric core, a hydrophilic linking agent bound to said polymeric core, and a biofunctional material bound to said linking agent, wherein said biofunctional material comprises a binding site for adhesins present on the surface of the biologically active microorganism.

[0060] In one embodiment, the nanoparticles of the present invention can target commensal microorganisms such as yeast or other fungi. For example, the yeast Candida albicans is a human commensal. The ability of Candida to adhere to the host is a fungal virulence factor similar to that of other microbial systems, and is considered a significant step in the development of candidiasis. The present invention can also target viral pathogens. In particular, the biofunctional materials on the surface of the nanoparticles can include those which can be recognized and bound by the pathogenic capsid surfaces of a virus. For example, the nanoparticles can be biofunctionalized so as to target various rotaviruses, Norwalk-like viruses, adenoviruses, astroviruses, coronaviruses, enteroviruses, or other viral agents. For example, in one embodiment, nanoparticles can be biofunctionalized with the GP120 protein of HIV to provide a particulate immunizing preparation.

Clemson patent filing link
http://tinyurl.com/2js8we