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RNA synthetic biology

Abstract

RNA molecules play important and diverse regulatory roles in the cell by virtue of their interaction with other nucleic acids, proteins and small molecules. Inspired by this natural versatility, researchers have engineered RNA molecules with new biological functions. In the last two years efforts in synthetic biology have produced novel, synthetic RNA components capable of regulating gene expression in vivo largely in bacteria and yeast, setting the stage for scalable and programmable cellular behavior. Immediate challenges for this emerging field include determining how computational and directed-evolution techniques can be implemented to increase the complexity of engineered RNA systems, as well as determining how such systems can be broadly extended to mammalian systems. Further challenges include designing RNA molecules to be sensors of intracellular and environmental stimuli, probes to explore the behavior of biological networks and components of engineered cellular control systems.

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Figure 1: Endogenous RNAs that regulate gene expression.
Figure 2: Engineered riboregulators.
Figure 3: Engineered ribosome-mRNA pairs.
Figure 4: Engineered ligand-controlled riboregulators.
Figure 5: Engineered ribozyme-mediated gene expression.
Figure 6: Engineered RNA transcriptional activators.
Figure 7: In vitro nucleic acid systems.

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Acknowledgements

We thank Jason Chin for providing access to unpublished results in the form of a preprint manuscript and George Church for insightful and relevant discussions. We also thank Nick Reppas, Duhee Bang and the anonymous reviewers for providing valuable suggestions to improve the paper. This work was supported by the National Institutes of Health and the National Science Foundation.

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Isaacs, F., Dwyer, D. & Collins, J. RNA synthetic biology. Nat Biotechnol 24, 545–554 (2006). https://doi.org/10.1038/nbt1208

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