Synthetic Antibodies
Pacific Northwest National Laboratory's new approach for generating synthetic antibodies uses high-speed flow cytometers, thus eliminating the use of live animals.Scientists at Pacific Northwest National Laboratory (PNNL) are developing technologies to generate high-affinity antibodies to serve as (1) molecular reagents to extend our fundamental understanding of biological processes and (2) recognition molecules to be integrated into sensors to detect biowarfare agents or various environmental contaminants.
PNNL biologists created libraries of synthetic antibodies through yeast surface display technologies. Standard monoclonal antibodies are often restricted to substances not normally found in the human body, while synthetic antibodies are generated in the laboratory without any constraints.
Coupling synthetic antibodies to the yeast display format allows selection of binders with a high affinity to their intended target—a substantial improvement over previous display systems. At PNNL, scientists adapt and adopt technologies that allow rapid affinity maturation of single synthetic antibody clones.
Ongoing efforts to improve the selection of synthetic antibody antigen-specific clones and enhance their functionality include:
- high-throughput screening and enrichment for synthetic antibodies against multiple antigens
- rapid clone identification, separation, and purification using magnetic bead and flow cytometry technologies
- affinity maturation and high-level expression of epitope-tagged synthethic antibodies.
Using these techniques, PNNL scientists can create antigen-specific reagents for use in the following:
- immunoprecipitation of protein complexes and subsequent identification of the components by mass spectrometry
- immunohistochemistry, cell staining, and flow cytometry
- protein antibody arrays and diagnostic reagents
- drug target validation
- therapeutics.
