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Engineered molecule amplifies body's immune response

lecule. By increasing the efficiency of the Stat1 molecule, the host could have the benefits of increased Stat1 signaling even at the low levels of interferon normally present in the body. Their results appear as the "Paper of the Week" in the October 7 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

"Our paper is really quite simple in conceptual terms," says Dr. Holtzman. "It is well known that interferon provides a benefit to people by protecting them against infectious diseases and cancer. Unfortunately, administration of interferon is costly and short-lived and has significant side effects. We simply reasoned that it might be possible to improve the benefits of interferon by enhancing the way it produces its beneficial effects. We therefore improved a molecule, known as Stat1, that is responsible for relaying the benefits of interferon in the body."

Their initial in vitro results were promising, and the engineered Stat1 molecule exhibited an increased responsiveness to interferon. Following up on these discoveries, Dr. Holtzman and his colleagues are currently performing gene transfer experiments, using both recombinant viruses and transgenic mice, to establish the benefits of hyper-responsive Stat1 in vivo for treating viral infection and cancer. They are also screening for drugs that might increase Stat1 responsiveness.

These experiments may eventually lead to many improvements in cancer therapy as well as the treatment of other infections. Basically, any situation in which interferon hyper-responsiveness might be beneficial will profit from Dr. Holtzman's research.

"One could use our strategy of improving Stat1 efficiency during the winter months in patients who are at risk for developing serious viral infections, for example children with asthma, or heart disease, or immune compromise," suggests Dr. Holtzman. "It may also be of benefit in situations where inter
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Source:American Society for Biochemistry and Molecular Biology


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