Synthetic antibody engineering: Concepts and applications

Monoclonal antibodies (mAbs) are widely used for diagnostic, research, and therapeutic applications. A critical performance feature of a mAb is its specificity toward a particular target. Here, we discuss the use of protein engineering methods (phage display and structure-based design) to develop novel mAbs, in some cases with exquisite specificity for particular target structural conformations, posttranslation modifications, or point mutations. The phage display libraries are designed and produced using synthetic oligonucleotides (synthetic antibodies), and the mAb identification procedure involves entirely in vitro screening methods. Therefore, the synthetic antibody approach allows stringent control over the state of the target during the antibody selection process. Furthermore, the libraries encode amino acid side chains that are biased toward residues with favorable physicochemical attributes for intermolecular recognition. Thus, the method is not biased by immunodominance and allows for identification of mAbs against targets that are intractable by other methods.