New DART VADAR system allows development of precision RNA-based therapies

This novel engineered system, in particular, would broaden the scope of developing RNA-based therapeutics for a wide range of diseases.Genetic circuits that control transgene expression in response to pre-defined transcriptional cues would enable the development of smart therapeutics. To this end, here we engineer programmable single-transcript RNA sensors in which adenosine deaminases acting on RNA autocatalytically convert target hybridization into a translational output.

Dubbed DART VADAR , our system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. Amplification is mediated by the expression of a hyperactive, minimal ADAR variant and its recruitment to the edit site via an orthogonal RNA targeting mechanism. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint.

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