A synthetic time-delay circuit in mammalian cells and mice

A synthetic mammalian gene circuit reveals antituberculosis compounds

“…Synthetic gene circuits have dramatically increased progress on gene-function relationships in the postgenomic era (8)(9)(10)(11)(21)(22)(23)(24)(25). They also continue to provide the key parts for synthetic biologists to decipher natural gene network dynamics (8)(9)(10) and to reprogram cellular function for production of important precursor drugs (23).…”

“…They also continue to provide the key parts for synthetic biologists to decipher natural gene network dynamics (8)(9)(10) and to reprogram cellular function for production of important precursor drugs (23). We have engineered a synthetic gene network in human cells for screening of functional antimicrobial agents with precise target specificity, undetectable cytotoxicity, and the capacity to reach the cytosol to eliminate intracellular pathogens.…”

“…Therefore, integrated screening approaches assessing specificity, bioavailability, and cytotoxicity in a single assay are expected to rapidly reveal valid drug candidates. Although synthetic mammalian gene networks designed so far, including epigenetic toggle switches (8), hysteresis networks (9), time-delay circuits (10), and synthetic ecosystems (11), have resulted in important information on the dynamics of physiologic control systems, the EthR-based gene circuit pioneers a direction with a more practical purpose: providing a generic screening platform to discover drug candidates with the potential to efficiently kill M. tuberculosis, the causative agent of one of the most devastating human diseases.…”

Mammalian synthetic biology: emerging medical applications

“…Moreover, similarly to electronic circuits, several multicomponent circuits with complex trigger-controlled topology have been designed with time-delay [116], bandpass [117] and hysteretic [118] properties. A gene network operated by a Boolean AND gate was applied for targeting cancer cells [119], where the AND gate activity was achieved when both pre-set conditions were met, leading to the expression of apoptotic genes and cancer cell death.…”

Genetically Programmable Pathogen Sense and Destroy

“…An optimized 'waiting period' can be introduced by synthetic cascades consisting of repressors (i.e. genetic logic inverters) connected in series [49,53,58,59,193,194]. This second stage attack will involve the sentinels bursting (using E-protein discussed in Chapter 2 Section III (a)), and releasing large quantities of a broader spectrum toxin into the medium to kill any remaining pathogen.…”