Sensors & Electronics
Awards & Recognition
R&D 100 Awards
2004 - Single-Chain Antibody Library
Developers: Michael J. Feldhaus (PNNL), K. Dane Wittrup (Massachusetts Institute of Technology), Lee K. Opresko (PNNL), Robert W. Siegel (PNNL), H. Steven Wiley (PNNL)
Developed by the Pacific Northwest National Laboratory (PNNL) and the Massachusetts Institute of Technology (MIT), the Single-Chain Antibody Library provides researchers with an easy-to-grow library of more than one billion artificial antibodies. These antibodies—produced by genetically engineered brewer's yeast—offer an inexpensive method for creating and producing antibodies for research. Antibodies play an increasingly important role in the biomedical and pharmaceutical industries as effective tools for recognizing specific molecules. For example, in medical treatments, antibodies are injected into the body to seek out specific proteins on cancerous cells, and target treatment to those cells. Biowarfare sensors can also use antibodies to detect proteins associated with harmful agents. Antibodies also are expected to play a major role in helping scientists to more fully understand various biological processes by identifying which proteins are present in a given functional state and if they interact with other specific proteins in the cell.
Nanomolar-affinity scFvs (single chain Fragment variables) are routinely obtained by magnetic bead screening and flow cytometric sorting. This yields clones of yeast cells that contain the gene encoding the scFv. The biochemical and biophysical properties of the scFv clones can be evaluated directly on the yeast cell surface by immunofluorescent labeling and flow cytometry, eliminating the separate subcloning, expression, and purification steps typically necessary to find and extract unique antibodies. Using multiple antigens to screen the library simultaneously saves the researcher an enormous amount of time—days as compared to weeks or months with other current technologies. The ability to use multiplex library screening allows this approach to be used for high-throughput antibody isolation necessary for proteomics applications.
PNNL's Single-Chain Antibody Library could replace the need to produce antibodies using animals and presents new possibilities for rapidly designing medical treatments more compatible with the human immune system. It provides greater benefit over similar but older technologies by: using a novel identification process that allows researchers to screen and identify needed antibodies, in days rather than months; saving research dollars by reducing time and labor cost; enabling the rapid reproduction of selected antibodies; and controlling the expression of antibodies to allow library expansion while maintaining diversity.
Excerpted from PNNL R&D 100 webpage.
Selected Links to Related Information:
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