Scripps finds way to fight future strains of flu

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       Scripps finds way to fight future strains of flu 

Tuesday, July 17, 2007

A team of scientists from The Scripps Research Institute has devised a way to generate drug candidates and antibodies against the business-end of the flu - long before some mutations appear in nature.

Their research, published this week in the Proceedings of the National Academy of Sciences, represents a first step toward Project Checkmate, a collaboration between Scripps and IBM that was announced in Boca Raton in the spring of 2006. Project Checkmate was proposed as a way to develop a national defensive stockpile of antibodies, drugs and vaccines against flu strains which may have pandemic potential but haven't yet materialized.

    The reason flu is so dangerous is that it's constantly changing, outrunning the vaccines and drugs designed to stop it. If the mutations could be predicted in advance, dangerous strains of disease could be stopped before spreading, the scientists believe.

Scripps and IBM have sent a grant proposal to the National Institutes of Health and are awaiting review. 

In the meantime, Scripps President Richard Lerner said he has moved forward with one small part of the Checkmate concept. Lerner worked on the research with Nobel Laureate Sydney Brenner, Scripps microbiologist Kim Janda and four others. 

The team took advantage of a microbiology tool called phage display. It employs a bacteria-infecting virus called a phage as a pawn to draw out antibodies or drugs that can thwart a truly dangerous virus. 

In this case, the scientists inserted a truncated flu gene into the phages, one that flu uses to latch onto and infect cells. 

They applied a solution of altered phages to red blood cells. The ones that latched onto the blood cells were deemed active. 

Next, those active flu-phages were washed in a solution of drug-like molecules selected for their likely action against the flu protein. Some of the phages escaped while others were ensnared by the molecules.

The flu-phages that the molecules latched onto could then be encouraged to proliferate and mutate and run through the process again and again, until a large library of mutations and drug candidates are cataloged, Lerner said. 

Repetition and expansion of the process could yield a collection of antibodies or drugs able to thwart a universe of possible but as-yet unseen flu strains. 

"In the entire history of vaccination, one studies what a virus has done rather than what it can do, and this is a switch," the scientists wrote.

Janda said he expects the method, which Scripps is seeking to patent, will gain widespread use. 

"Anybody with a molecular biology background can probably do this," Janda said. "The goal for most drug companies is efficiency, cost-effectiveness and speed in churning out things that are useful, and I think this has all the things you need."

The method could prove useful in defending against flu or other diseases, Lerner said.

"It's a predictive tool to anticipate how viruses will evolve," Lerner said.

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	Scripps finds way to fight future strains of flu Tuesday, July 17, 2007 A team of scientists from The Scripps Research Institute has devised a way to generate drug candidates and antibodies against the business-end of the flu - long before some mutations appear in nature. Their research, published this week in the Proceedings of the National Academy of Sciences, represents a first step toward Project Checkmate, a collaboration between Scripps and IBM that was announced in Boca Raton in the spring of 2006. Project Checkmate was proposed as a way to develop a national defensive stockpile of antibodies, drugs and vaccines against flu strains which may have pandemic potential but haven't yet materialized. The reason flu is so dangerous is that it's constantly changing, outrunning the vaccines and drugs designed to stop it. If the mutations could be predicted in advance, dangerous strains of disease could be stopped before spreading, the scientists believe. Scripps and IBM have sent a grant proposal to the National Institutes of Health and are awaiting review. In the meantime, Scripps President Richard Lerner said he has moved forward with one small part of the Checkmate concept. Lerner worked on the research with Nobel Laureate Sydney Brenner, Scripps microbiologist Kim Janda and four others. The team took advantage of a microbiology tool called phage display. It employs a bacteria-infecting virus called a phage as a pawn to draw out antibodies or drugs that can thwart a truly dangerous virus. In this case, the scientists inserted a truncated flu gene into the phages, one that flu uses to latch onto and infect cells. They applied a solution of altered phages to red blood cells. The ones that latched onto the blood cells were deemed active. Next, those active flu-phages were washed in a solution of drug-like molecules selected for their likely action against the flu protein. Some of the phages escaped while others were ensnared by the molecules. The flu-phages that the molecules latched onto could then be encouraged to proliferate and mutate and run through the process again and again, until a large library of mutations and drug candidates are cataloged, Lerner said. Repetition and expansion of the process could yield a collection of antibodies or drugs able to thwart a universe of possible but as-yet unseen flu strains. "In the entire history of vaccination, one studies what a virus has done rather than what it can do, and this is a switch," the scientists wrote. Janda said he expects the method, which Scripps is seeking to patent, will gain widespread use. "Anybody with a molecular biology background can probably do this," Janda said. "The goal for most drug companies is efficiency, cost-effectiveness and speed in churning out things that are useful, and I think this has all the things you need." The method could prove useful in defending against flu or other diseases, Lerner said. "It's a predictive tool to anticipate how viruses will evolve," Lerner said.