Autocatalytic base editing for RNA-responsive translational control

Genetic circuits that control transgene expression in response to pre-defined transcriptional cues would enable the development of smart therapeutics. To this end, here Jim Collins, faculty lead for life sciences at MIT Jameel Clinic and colleagues at Harvard Wyss Institute engineer programmable single-transcript RNA sensors in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert target hybridisation into a translational output. Dubbed DART VADAR (Detection and Amplification of RNA Triggers via ADAR), the system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. The researchers leverage DART VADAR to detect single nucleotide polymorphisms and modulate translation in response to endogenous transcript levels in mammalian cells.