Toward a world of theranostic medication: Programming biological sentinel systems for therapeutic intervention

Theranostic systems support diagnostic and therapeutic functions in a single integrated entity and enable precise spatiotemporal control of the generation of therapeutic molecules according to the individual patient's disease state, thereby maximizing the therapeutic outcome and minimizing side effects. These systems can also incorporate reporter systems equipped with a disease-sensing module that can be used to estimate the efficacy of treatment in vivo. Among these reporter systems, biological sentinel systems, such as viruses, bacteria, and mammalian cells, have great potential for use in the development of novel theranostic systems because of their ability to sense a variety of disease markers and secrete various therapeutic molecules. Furthermore, recent advances in biotechnology and synthetic biology have made it possible to treat these biological systems as true programmable entities capable of conducting complex operations, to accurately identify each individual patient's disease state. In this review, we introduce the basic design principles of these rapidly expanding classes of biological sentinel system-based theranostic agents, with a focus on recent advances, and we also discuss potential enabling technologies that can further improve these systems and provide more sophisticated therapeutic interventions in the near future. In addition, we consider the possibility of synergistic use of theranostic agents that use different modalities and discuss the prospects for next-generation theranostic agents.