Engineering Gene Circuits for Mammalian Cell–Based Applications

Synthetic gene switches are basic building blocks for the construction of complex gene circuits that transform mammalian cells into useful cell-based machines for next-generation biotechnological and biomedical applications. Ligand-responsive gene switches are cellular sensors that are able to process specific signals to generate gene product responses. Their involvement in complex gene circuits results in sophisticated circuit topologies that are reminiscent of electronics and that are capable of providing engineered cells with the ability to memorize events, oscillate protein production, and perform complex information-processing tasks. Microencapsulated mammalian cells that are engineered with closed-loop gene networks can be implanted into mice to sense disease-related input signals and to process this information to produce a custom, fine-tuned therapeutic response that rebalances animal metabolism. Progress in gene circuit design, in combination with recent breakthroughs in genome engineering, may result in tailored engineered mammalian cells with great potential for future cell-based therapies.