Negative design for improved therapeutic proteins

Two recent papers describe noncanonical strategies for improvement of the pharmacokinetic properties of important therapeutic proteins. Although the detailed biologies of the two systems are very different, the unifying feature of both studies is the use of negative design principles. Rather than enhancing specific activity, the central strategy was the removal of states that compromise efficacy. These studies highlight the use of rational engineering and the benefits of firmly understanding the in vivo clearance biology of a biotherapeutic.