Expert view: Engineered antibodies: semi-rational design approach for faster optimisation
A significant hurdle in optimising antibody therapeutics is the screening of successive rounds of large libraries of mutant variants in order to recognise the ideal candidate.
Here, we discuss how a semi-rational design approach can create diverse mutant libraries, significantly reducing the overall screening effort and leading to faster identification of the optimal drug candidate.
Antibody-based drug candidates require additional engineering to improve stability, solubility and target affinity, as well as decrease immunogenicity. To identify the ideal optimised drug candidate, antibody engineers use a technique called directed evolution that requires high-throughput approaches to create and screen a large library of mutant variants. Mutant libraries are generated in large scales using polymerase chain reaction (PCR), cloned into expression vectors and screened via phage or yeast display.