Integrating synthetic biology to understand and engineer the heart, lung, blood, and sleep systems

Synthetic biology offers control over cellular and tissue functions. As it moves beyond microbes into humans, synthetic biology enables precise control over gene expression, cell fate, and tissue organization across heart, lung, blood, and sleep systems. By integrating genome engineering, dynamic gene circuits, and high-dimensional biosensors, these advances support scalable, quantitative models of multicellular biology, expanding the need for systems-level models and integration. We highlight emerging systems such as tunable transcriptional regulators, synthetic organizers, and feedback circuits that bridge molecular control with functional outcomes. Furthermore, by combining omics data with artificial intelligence (AI)-guided circuit design, synthetic biology enables high-resolution cellular and tissue-scale models of development, cellular interactions, drug development, gene therapy, and therapeutic response. Key challenges remain-including delivery, transgene stability, and robust spatiotemporal control in physiologically relevant models. This perspective synthesizes field-spanning progress and defines shared priorities for engineering cells and tissues that function reliably across dynamic, multi-organ environments.