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Scripps Research scientists devise powerful new method for finding therapeutic antibodies
Date:9/11/2012

no significant EPO-mimicking effect. Further tests showed that the source of the EPO-mimicking effect in the test cells was an antibody that does not occur naturally.

An antibody of the type used in the study has a Y-shaped structure, normally with two identical binding arms. But the presence of multiple antibody genes within some of Zhang's test cells meant that, in a few cases, antibodies assembled themselves with two different binding arms. One of these "bispecific" antibodies turned out to bind to the EPO receptor which has two binding sites in a way that very accurately mimics the binding of a natural EPO molecule. "It turned out to be 100 percent as potent as authentic EPO in further tests," Zhang said.

The serendipitous finding represents another major innovation, for, in principle, it extends the medical and scientific antibody repertoire from the 100 billion or so known variants of same-armed antibodies to an astronomically higher number of bispecific variants. Experiments to test such variants will be limited by the maximum number of usable cells in cultures, but that number is still very high, on the order of 10 million. "That allows for a lot of unique binding events," said Lerner. "You probably can get almost anything that way."

Lerner emphasizes that this new antibody-engineering/discovery technique can be used not just against known targets such as the EPO receptor, but also against cellular functions involving targets that have not yet been found. "The real power of this technique is its ability to help us discover the unknown," he said.


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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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