Toehold Switches: De-Novo-Designed Regulators of Gene Expression
By Alexander A. Green, Pamela A. Silver, James J. Collins, Peng Yin. Cell, 2014
731 citations recorded by the source corpus.
SUMMARY Efforts to construct synthetic networks in living cells have been hindered by the limited number of regulatory components that provide wide dynamic range and low crosstalk. Here, we report a new class of de-novo-designed prokaryotic riboregulators called toehold switches that activate gene expression in response to cognate RNAs with arbitrary sequences. Toehold switches provide a high level of orthogonality and can be forward-engineered to provide average dynamic range above 400. We show that switches can be integrated into the genome to regulate endogenous genes and use them as sensors that respond to endogenous RNAs. We exploit the orthogonality of toehold switches to regulate 12 genes independently and to construct a genetic circuit that evaluates 4-input AND logic. Toehold switches, with their wide dynamic range, orthogonality, and programmability, represent a versatile and powerful platform for regulation of translation, offering diverse applications in molecular biology, synthetic biology, and biotechnology.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/9b0d31d71977bc2c8302f390d12e25550d4344c5
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In Molecular Biology
- Alexander A. Green
- James J. Collins
- Pamela A. Silver
- Peng Yin
- D. Cameron
- Tom Ferrante
- Keith Pardee
- A. DaleyKeyser
Citations in the corpus
- Paper-based Synthetic Gene Networks (2014, positive): “It is also of note that switch behavior in freeze-dried lysates replicates that of toehold switches in vivo in E. coli (Figure S2C; Green et al., 2014).”
- Complex cellular logic computation using ribocomputing devices (2017, methodology): “These performance levels are better than previous toehold-switch-based layered four-input AND gates 17 .”
- Rapid, Low-Cost Detection of Zika Virus Using Programmable Biomolecular Components. (2016, positive): “Upon a switch binding to a complementary trigger RNA, sequestration of the RBS and start codon is relieved, activating gene translation (Figures 2A and 2B) (Green et al., 2014).”