Year: 2023
Type: article
Abstract: 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 (ADARs) autocatalytically convert target hybridization into a translational output. Dubbed DART VADAR (Detection and Amplification of RNA Triggers via ADAR), 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. We leverage DART VADAR to detect single nucleotide polymorphisms and modulate translation in response to endogenous transcript levels in mammalian cells.
Source: Nature Communications
Language: English
Topic: RNA regulation and disease
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: U.S. Department of Health and Human Services, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, National Institutes of Health, Hansjörg Wyss Institute for Biologically Inspired Engineering, Harvard University, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Biomedical Imaging and Bioengineering
OpenAlex ID: W4323925127