Opportunities for artificial intelligence and synthetic biology in designing living drug delivery systems

Advances in artificial intelligence (AI) and synthetic biology are transforming biological research and biotechnology. These fields are for the first time enabling the design and development of human and bacterial cells that can serve as "living" drug delivery vehicles that perform sustained release of therapeutic cargo with spatiotemporal control. In recent years, human and bacterial cells have been engineered to deliver peptides, proteins, and biologics for treating a wide range of human diseases using synthetic biology approaches. To engineer effective living drug delivery systems, detailed knowledge is required about how to design receptors that can specifically sense the tissues targeted for drug delivery, signaling networks that can process signals from these receptors, and gene circuits that can control therapeutic cargo production and release. However, elucidating such receptors, signal processing and gene regulatory elements, and gene circuit compositions by traditional design-build-test-learn approaches is difficult and low throughput. Here we review how advances in AI and synthetic biology are meeting these challenges. We describe examples of how human cells and bacteria are engineered to become living drug delivery vehicles. We discuss how AI and synthetic biology approaches are being applied to discover the sequence-to-function design principles for engineering synthetic receptors, signaling proteins, and gene regulatory elements and the composition-to-function design principles for engineering synthetic gene circuits. We share an outlook on opportunities for AI and synthetic biology to synergize for creating next-generation living drug delivery systems.