Realizing Antithetic Integral Feedback Control in Mammalian Cells

Genetic circuit engineering has emerged as a powerful methodology to program the behavior of mammalian cells to respond to internal and external cues. This approach is now used to develop new therapeutics and improve production processes. However, genetic interaction networks are complex and hard to engineer rationally. Moreover, a design may fail, and it may not be possible to identify the root cause of its breakdown. Introducing designated regulatory circuitry in the form of integral feedback can introduce performance guarantees by ensuring robust and precise operation.