Affinity maturation by semi-rational approaches

Rational engineering methods can be applied with success to optimize physicochemical characteristics of antibodies. Application of in silico analysis and prediction methods to antibody Fv regions can help to find residues affecting antibody-antigen affinity when high-resolution antibody structures or antibody-antigen complex structures are known. In these cases, the identification of residues affecting affinity can facilitate the selection of candidates for guided maturation by PCR using degenerate oligonucleotides. Here, we describe the utilization of a semi-rational approach to enhance the affinity of antibodies by combining in silico and traditional wet lab-based methods.