In Vivo Applications of Bioorthogonal Reactions: Chemistry and Targeting Mechanisms
Madonna M. A. Mitry, Francesca Greco, Helen M. I. Osborn
Abstract
Bioorthogonal chemistry involves selective biocompatible reactions between functional groups that are not normally present in biology. It has been used to probe biomolecules in living systems, and has advanced biomedical strategies such as diagnostics and therapeutics. In this review, the challenges and opportunities encountered when translating in vitro bioorthogonal approaches to in vivo settings are presented, with a focus on methods to deliver the bioorthogonal reaction components. These methods include metabolic bioengineering, active targeting, passive targeting, and simultaneously used strategies. The suitability of bioorthogonal ligation reactions and bond cleavage reactions for in vivo applications is critically appraised, and practical considerations such as the optimum scheduling regimen in pretargeting approaches are discussed. Finally, we present our own perspectives for this area and identify what, in our view, are the key challenges that must be overcome to maximise the impact of these approaches.