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Scripps Research Institute Scientists Find Antibody that Transforms Bone Marrow Stem Cells Directly into Brain Cells
Date:4/22/2013

cultures in the laboratory. That has allowed them to start using this vast, target-gripping toolkit to make scientific probes, as well as diagnostics and therapies for cancer, arthritis, transplant rejection, viral infections and other diseases.

In the late 1980s, Lerner and his TSRI colleagues helped invent the first techniques for generating large "libraries" of distinct antibodies and swiftly determining which of these could bind to a desired target. The anti-inflammatory antibody Humira®, now one of the world's top-selling drugs, was discovered with the benefit of this technology.

Last year, in a study spearheaded by TSRI Research Associate Hongkai Zhang, Lerner's laboratory devised a new antibody-discovery technique—in which antibodies are produced in mammalian cells along with receptors or other target molecules of interest. The technique enables researchers to determine rapidly not just which antibodies in a library bind to a given receptor, for example, but also which ones activate the receptor and thereby alter cell function.

Lab Dish in a Cell

For the new study, Lerner laboratory Research Associate Jia Xie and colleagues modified the new technique so that antibody proteins produced in a given cell are physically anchored to the cell's outer membrane, near its target receptors. "Confining an antibody's activity to the cell in which it is produced effectively allows us to use larger antibody libraries and to screen these antibodies more quickly for a specific activity," said Xie. With the improved technique, scientists can sift through a library of tens of millions of antibodies in a few days.

In an early test, Xie used the new method to screen for antibodies that could activate the GCSF receptor, a growth-factor receptor found on bone marrow cells and other cell types. GCSF-mimicking drugs were among the first biotech bestsellers because of their ability to stimulate white blood cell growth—which counterac
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