Preloader

Engineering synthetic RNA devices for cell control

  • 1.

    Nshogozabahizi, J. C., Aubrey, K. L., Ross, J. A. & Thakor, N. Applications and limitations of regulatory RNA elements in synthetic biology and biotechnology. J. Appl. Microbiol. 127, 968–984 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • 2.

    Kim, J. & Franco, E. RNA nanotechnology in synthetic biology. Curr. Opin. Biotechnol. 63, 135–141 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • 3.

    Schmidt, C. M. & Smolke, C. D. RNA switches for synthetic biology. Cold Spring Harb. Perspect. Biol. 11, 135–141 (2019).

    Google Scholar 

  • 4.

    Park, S. V. et al. Catalytic RNA, ribozyme, and its applications in synthetic biology. Biotechnol. Adv. 37, 107452 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • 5.

    Win, M. N., Liang, J. C. & Smolke, C. D. Frameworks for programming biological function through RNA parts and devices. Chem. Biol. 16, 298–310 (2009).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 6.

    Liang, J. C., Bloom, R. J. & Smolke, C. D. Engineering biological systems with synthetic RNA molecules. Mol. Cell 43, 915–926 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 7.

    Nahvi, A. et al. Genetic control by a metabolite binding mRNA. Chem. Biol. 9, 1043–1049 (2002).

    CAS 
    PubMed 

    Google Scholar 

  • 8.

    Winkler, W. C., Cohen-Chalamish, S. & Breaker, R. R. An mRNA structure that controls gene expression by binding FMN. Proc. Natl Acad. Sci. USA 99, 15908–15913 (2002).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 9.

    Sudarsan, N., Barrick, J. E. & Breaker, R. R. Metabolite-binding RNA domains are present in the genes of eukaryotes. RNA 9, 644–647 (2003).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 10.

    Isaacs, F. J. et al. Engineered riboregulators enable post-transcriptional control of gene expression. Nat. Biotechnol. 22, 841–847 (2004).

    CAS 
    PubMed 

    Google Scholar 

  • 11.

    Suess, B. & Weigand, J. E. Engineered riboswitches: overview, problems and trends. RNA Biol. 5, 24–29 (2008).

    CAS 
    PubMed 

    Google Scholar 

  • 12.

    McKeague, M., Wong, R. S. & Smolke, C. D. Opportunities in the design and application of RNA for gene expression control. Nucleic Acids Res. 44, 2987–2999 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 13.

    Westbrook, A. M. & Lucks, J. B. Achieving large dynamic range control of gene expression with a compact RNA transcription–translation regulator. Nucleic Acids Res. 45, 5614–5624 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 14.

    Kim, J. et al. De novo-designed translation-repressing riboregulators for multi-input cellular logic. Nat. Chem. Biol. 15, 1173–1182 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 15.

    Rauch, S., Jones, K. A. & Dickinson, B. C. Small molecule-inducible RNA-targeting systems for temporal control of RNA regulation. ACS Cent. Sci. 6, 1987–1996 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 16.

    Chappell, J., Westbrook, A., Verosloff, M. & Lucks, J. B. Computational design of small transcription activating RNAs for versatile and dynamic gene regulation. Nat. Commun. 8, 1051 (2017).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 17.

    Anzalone, A. V., Lin, A. J., Zairis, S., Rabadan, R. & Cornish, V. W. Reprogramming eukaryotic translation with ligand-responsive synthetic RNA switches. Nat. Methods 13, 453–458 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 18.

    Spöring, M., Finke, M. & Hartig, J. S. Aptamers in RNA-based switches of gene expression. Curr. Opin. Biotechnol. 63, 34–40 (2020).

    PubMed 

    Google Scholar 

  • 19.

    Kawasaki, S., Ono, H., Hirosawa, M. & Saito, H. RNA and protein-based nanodevices for mammalian post-transcriptional circuits. Curr. Opin. Biotechnol. 63, 99–110 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • 20.

    Endy, D. Foundations for engineering biology. Nature 438, 449–453 (2005).

    CAS 
    PubMed 

    Google Scholar 

  • 21.

    Barrick, J. E. & Breaker, R. R. The distributions, mechanisms, and structures of metabolite-binding riboswitches. Genome Biol. 8, R239 (2007).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 22.

    Ellington, A. D. & Szostak, J. W. In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818–822 (1990).

    CAS 
    PubMed 

    Google Scholar 

  • 23.

    Lauridsen, L. H., Doessing, H. B., Long, K. S. & Nielsen, A. T. in Synthetic Metabolic Pathways: Methods and Protocols (eds. Jensen, M. K. & Keasling, J. D.) 291–306 (Springer, 2018).

  • 24.

    Baird, G. S. Where are all the aptamers? Am. J. Clin. Pathol. 134, 529–531 (2010).

    PubMed 

    Google Scholar 

  • 25.

    Dunn, M. R., Jimenez, R. M. & Chaput, J. C. Analysis of aptamer discovery and technology. Nat. Rev. Chem. 1, 0076 (2017).

    CAS 

    Google Scholar 

  • 26.

    McKeague, M. & DeRosa, M. C. Challenges and opportunities for small molecule aptamer development. J. Nucleic Acids 2012, 1–20 (2012).

    Google Scholar 

  • 27.

    McKeague, M. et al. Analysis of in vitro aptamer selection parameters. J. Mol. Evol. 81, 150–161 (2015).

    CAS 
    PubMed 

    Google Scholar 

  • 28.

    Valencia-Sanchez, M. A., Liu, J., Hannon, G. J. & Parker, R. Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 20, 515–524 (2006).

    CAS 
    PubMed 

    Google Scholar 

  • 29.

    Bloom, R. J., Winkler, S. M. & Smolke, C. D. Synthetic feedback control using an RNAi-based gene-regulatory device. J. Biol. Eng. 9, 5 (2015).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 30.

    Lucks, J. B., Qi, L., Mutalik, V. K., Wang, D. & Arkin, A. P. Versatile RNA-sensing transcriptional regulators for engineering genetic networks. Proc. Natl Acad. Sci. USA 108, 8617–8622 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 31.

    Ausländer, S. & Fussenegger, M. Synthetic RNA-based switches for mammalian gene expression control. Curr. Opin. Biotechnol. 48, 54–60 (2017).

    PubMed 

    Google Scholar 

  • 32.

    Chappell, J. et al. The centrality of RNA for engineering gene expression. Biotechnol. J. 8, 1379–1395 (2013).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 33.

    Till, P., Toepel, J., Bühler, B., Mach, R. L. & Mach-Aigner, A. R. Regulatory systems for gene expression control in cyanobacteria. Appl. Microbiol. Biotechnol. 104, 1977–1991 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 34.

    Bayer, T. S. & Smolke, C. D. Programmable ligand-controlled riboregulators of eukaryotic gene expression. Nat. Biotechnol. 23, 337–343 (2005).

    CAS 
    PubMed 

    Google Scholar 

  • 35.

    Kawasaki, S., Fujita, Y., Nagaike, T., Tomita, K. & Saito, H. Synthetic mRNA devices that detect endogenous proteins and distinguish mammalian cells. Nucleic Acids Res. 45, e117–e117 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 36.

    Paige, J. S., Nguyen-Duc, T., Song, W. & Jaffrey, S. R. Fluorescence imaging of cellular metabolites with RNA. Science 335, 1194–1194 (2012).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 37.

    Jepsen, M. D. E. et al. Development of a genetically encodable FRET system using fluorescent RNA aptamers. Nat. Commun. 9, 18 (2018).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 38.

    Wurmthaler, L. A., Sack, M., Gense, K., Hartig, J. S. & Gamerdinger, M. A tetracycline-dependent ribozyme switch allows conditional induction of gene expression in Caenorhabditis elegans. Nat. Commun. 10, 491 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 39.

    Gu, H., Furukawa, K. & Breaker, R. R. Engineered allosteric ribozymes that sense the bacterial second messenger cyclic diguanosyl 5′-monophosphate. Anal. Chem. 84, 4935–4941 (2012).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 40.

    Niu, T. et al. Engineering a glucosamine-6-phosphate responsive glmS ribozyme switch enables dynamic control of metabolic flux in Bacillus subtilis for overproduction of N-acetylglucosamine. ACS Synth. Biol. 7, 2423–2435 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • 41.

    Sterner, R. C. & Sterner, R. M. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 11, 1–11 (2021).

    Google Scholar 

  • 42.

    Di Stasi, A. et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl. J. Med. 365, 1673–1683 (2011).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 43.

    Chen, Y. Y., Jensen, M. C. & Smolke, C. D. Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems. Proc. Natl Acad. Sci. USA 107, 8531–8536 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 44.

    Wong, R. S., Chen, Y. Y. & Smolke, C. D. Regulation of T cell proliferation with drug-responsive microRNA switches. Nucleic Acids Res. 46, 1541–1552 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • 45.

    Liu, Y. et al. Directing cellular information flow via CRISPR signal conductors. Nat. Methods 13, 938–944 (2016).

    CAS 
    PubMed 

    Google Scholar 

  • 46.

    Liu, Y. et al. Engineering cell signaling using tunable CRISPR–Cpf1-based transcription factors. Nat. Commun. 8, 2095 (2017).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 47.

    Tang, W., Hu, J. H. & Liu, D. R. Aptazyme-embedded guide RNAs enable ligand-responsive genome editing and transcriptional activation. Nat. Commun. 8, 15939 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 48.

    Hoffmann, M. D. et al. Cell-specific CRISPR–Cas9 activation by microRNA-dependent expression of anti-CRISPR proteins. Nucleic Acids Res. 47, e75 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 49.

    Hirosawa, M. et al. Cell-type-specific genome editing with a microRNA-responsive CRISPR–Cas9 switch. Nucleic Acids Res. 45, e118 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 50.

    Hirosawa, M., Fujita, Y. & Saito, H. Cell-type-specific CRISPR activation with microRNA-responsive AcrllA4 switch. ACS Synth. Biol. 8, 1575–1582 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • 51.

    Lee, J. et al. Tissue-restricted genome editing in vivo specified by microRNA-repressible anti-CRISPR proteins. RNA 25, 1421–1431 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 52.

    Davis, K. M., Pattanayak, V., Thompson, D. B., Zuris, J. A. & Liu, D. R. Small molecule-triggered Cas9 protein with improved genome-editing specificity. Nat. Chem. Biol. 11, 316–318 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 53.

    Robbins, P. D., Tahara, H. & Ghivizzani, S. C. Viral vectors for gene therapy. Trends Biotechnol. 16, 35–40 (1998).

    CAS 
    PubMed 

    Google Scholar 

  • 54.

    Strobel, B. et al. Riboswitch-mediated attenuation of transgene cytotoxicity increases adeno-associated virus vector yields in HEK-293 cells. Mol. Ther. 23, 1582–1591 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 55.

    Takahashi, K. & Yokobayashi, Y. Reversible gene regulation in mammalian cells using riboswitch-engineered vesicular stomatitis virus vector. ACS Synth. Biol. 8, 1976–1982 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • 56.

    Reid, C. A., Nettesheim, E. R., Connor, T. B. & Lipinski, D. M. Development of an inducible anti-VEGF rAAV gene therapy strategy for the treatment of wet AMD. Sci. Rep. 8, 11763 (2018).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 57.

    Strobel, B. et al. A small-molecule-responsive riboswitch enables conditional induction of viral vector-mediated gene expression in mice. ACS Synth. Biol. 9, 1292–1305 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • 58.

    Han, S. R. et al. Targeted suicide gene therapy for liver cancer based on ribozyme-mediated RNA replacement through post-transcriptional regulation. Mol. Ther. Nucleic Acids 23, 154–168 (2021).

    CAS 
    PubMed 

    Google Scholar 

  • 59.

    Wang, H. et al. Characterization of a bifunctional synthetic RNA aptamer and a truncated form for ability to inhibit growth of non-small cell lung cancer. Sci. Rep. 9, 18836 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 60.

    Worgall, S., Wolff, G., Falck-Pedersen, E. & Crystal, R. G. Innate immune mechanisms dominate elimination of adenoviral vectors following in vivo administration. Hum. Gene Ther. 8, 37–44 (1997).

    CAS 
    PubMed 

    Google Scholar 

  • 61.

    Uehata, T. & Takeuchi, O. RNA recognition and immunity-innate immune sensing and its posttranscriptional regulation mechanisms. Cells 9, E1701 (2020).

    PubMed 

    Google Scholar 

  • 62.

    Ireton, R. C., Wilkins, C. & Gale, M. RNA PAMPs as molecular tools for evaluating RIG-I function in innate immunity. Methods Mol. Biol. 1656, 119–129 (2017).

    CAS 
    PubMed 

    Google Scholar 

  • 63.

    Kell, A. M. & Gale, M. RIG-I in RNA virus recognition. Virology 479–480, 110–121 (2015).

    PubMed 

    Google Scholar 

  • 64.

    Wu, M. Z., Asahara, H., Tzertzinis, G. & Roy, B. Synthesis of low immunogenicity RNA with high-temperature in vitro transcription. RNA 26, 345–360 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 65.

    Andries, O. et al. N1-Methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. J. Control. Rel. 217, 337–344 (2015).

    CAS 

    Google Scholar 

  • 66.

    Karikó, K. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008).

    PubMed 

    Google Scholar 

  • 67.

    Wesselhoeft, R. A. et al. RNA circularization diminishes immunogenicity and can extend translation duration in vivo. Mol. Cell 74, 508–520.e4 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 68.

    Pardi, N., Hogan, M. J. & Weissman, D. Recent advances in mRNA vaccine technology. Curr. Opin. Immunol. 65, 14–20 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • 69.

    Wadhwa, A., Aljabbari, A., Lokras, A., Foged, C. & Thakur, A. Opportunities and challenges in the delivery of mRNA-based vaccines. Pharmaceutics 12, E102 (2020).

    PubMed 

    Google Scholar 

  • 70.

    Dua, P., Kim, S. & Lee, D. Nucleic acid aptamers targeting cell-surface proteins. Methods 54, 215–225 (2011).

    CAS 
    PubMed 

    Google Scholar 

  • 71.

    Narberhaus, F., Waldminghaus, T. & Chowdhury, S. RNA thermometers. FEMS Microbiol. Rev. 30, 3–16 (2006).

    CAS 
    PubMed 

    Google Scholar 

  • 72.

    Neupert, J., Karcher, D. & Bock, R. Design of simple synthetic RNA thermometers for temperature-controlled gene expression in Escherichia coli. Nucleic Acids Res. 36, e124–e124 (2008).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 73.

    Lotz, T. S. et al. A light-responsive RNA aptamer for an azobenzene derivative. Nucleic Acids Res. 47, 2029–2040 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • 74.

    Gold, L. et al. Aptamer-based multiplexed proteomic technology for biomarker discovery. PLoS ONE 5, e15004 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 75.

    Darmostuk, M., Rimpelova, S., Gbelcova, H. & Ruml, T. Current approaches in SELEX: an update to aptamer selection technology. Biotechnol. Adv. 33, 1141–1161 (2015).

    CAS 
    PubMed 

    Google Scholar 

  • 76.

    Wayment-Steele, H., Wu, M., Gotrik, M. & Das, R. in Methods in Enzymology Vol. 623 Ch. 18 (ed. Hargrove, A. E.) 417–450 (Academic, 2019).

  • 77.

    Davis, J. H. & Szostak, J. W. Isolation of high-affinity GTP aptamers from partially structured RNA libraries. Proc. Natl Acad. Sci. USA 99, 11616–11621 (2002).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 78.

    Kohlberger, M. & Gadermaier, G. SELEX: critical factors and optimization strategies for successful aptamer selection. Biotechnol. Appl. Biochem. https://doi.org/10.1002/bab.2244 (2021).

    Article 
    PubMed 

    Google Scholar 

  • 79.

    Komarova, N. & Kuznetsov, A. Inside the black box: what makes SELEX better? Molecules 24, E3598 (2019).

    PubMed 

    Google Scholar 

  • 80.

    Ricci, F., Vallée-Bélisle, A., Simon, A. J., Porchetta, A. & Plaxco, K. W. Using nature’s “tricks” to rationally tune the binding properties of biomolecular receptors. Acc. Chem. Res. 49, 1884–1892 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 81.

    Townshend, B., Xiang, J. S., Manzanarez, G., Hayden, E. J. & Smolke, C. D. A multiplexed, automated evolution pipeline enables scalable discovery and characterization of biosensors. Nat. Commun. 12, 1437 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 82.

    Hasegawa, H., Savory, N., Abe, K. & Ikebukuro, K. Methods for improving aptamer binding affinity. Molecules 21, 421 (2016).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 83.

    Kalra, P., Dhiman, A., Cho, W. C., Bruno, J. G. & Sharma, T. K. Simple methods and rational design for enhancing aptamer sensitivity and specificity. Front. Mol. Biosci. 5, 41 (2018).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 84.

    Stoltenburg, R., Nikolaus, N. & Strehlitz, B. Capture-SELEX: selection of DNA aptamers for aminoglycoside antibiotics. J. Anal. Methods Chem. 2012, 1–14 (2012).

    Google Scholar 

  • 85.

    Boussebayle, A., Groher, F. & Suess, B. RNA-based Capture-SELEX for the selection of small molecule-binding aptamers. Methods 161, 10–15 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • 86.

    Koizumi, M., Soukup, G. A., Kerr, J. N. & Breaker, R. R. Allosteric selection of ribozymes that respond to the second messengers cGMP and cAMP. Nat. Struct. Biol. 6, 1062–1071 (1999).

    CAS 
    PubMed 

    Google Scholar 

  • 87.

    Xiang, J. S. et al. Massively parallel RNA device engineering in mammalian cells with RNA-seq. Nat. Commun. 10, 4327 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 88.

    Strobel, B. et al. High-throughput identification of synthetic riboswitches by barcode-free amplicon-sequencing in human cells. Nat. Commun. 11, 1–12 (2020).

    Google Scholar 

  • 89.

    Townshend, B., Kennedy, A. B., Xiang, J. S. & Smolke, C. D. High-throughput cellular RNA device engineering. Nat. Methods 12, 989–994 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 90.

    Nomura, Y., Chien, H.-C. & Yokobayashi, Y. Direct screening for ribozyme activity in mammalian cells. Chem. Commun. 53, 12540–12543 (2017).

    CAS 

    Google Scholar 

  • 91.

    Gotrik, M. et al. Direct selection of fluorescence-enhancing RNA aptamers. J. Am. Chem. Soc. 140, 3583–3591 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • 92.

    Zhao, B. S., Roundtree, I. A. & He, C. Post-transcriptional gene regulation by mRNA modifications. Nat. Rev. Mol. Cell Biol. 18, 31–42 (2017).

    CAS 
    PubMed 

    Google Scholar 

  • 93.

    Holley, R. W., Everett, G. A., Madison, J. T. & Zamir, A. Nucleotide sequences in the yeast alanine transfer ribonucleic acid. J. Biol. Chem. 240, 2122–2128 (1965).

    CAS 
    PubMed 

    Google Scholar 

  • 94.

    Pereira, M. et al. Impact of tRNA modifications and tRNA-modifying enzymes on proteostasis and human disease. Int. J. Mol. Sci. 19, E3738 (2018).

    PubMed 

    Google Scholar 

  • 95.

    Dominissini, D. et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485, 201–206 (2012).

    CAS 
    PubMed 

    Google Scholar 

  • 96.

    Meyer, K. D. et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149, 1635–1646 (2012).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 97.

    Jaffrey, S. R. & Kharas, M. G. Emerging links between m6A and misregulated mRNA methylation in cancer. Genome Med. 9, 2 (2017).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 98.

    Liu, J. et al. A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10, 93–95 (2014).

    CAS 
    PubMed 

    Google Scholar 

  • 99.

    Wilson, C., Chen, P. J., Miao, Z. & Liu, D. R. Programmable m6A modification of cellular RNAs with a Cas13-directed methyltransferase. Nat. Biotechnol. 38, 1431–1440 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 100.

    Xiao, W. et al. Nuclear m6A reader YTHDC1 regulates mRNA splicing. Mol. Cell 61, 507–519 (2016).

    CAS 
    PubMed 

    Google Scholar 

  • 101.

    Rees, H. A. & Liu, D. R. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat. Rev. Genet. 19, 770–788 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 102.

    Marina, R. J., Brannan, K. W., Dong, K. D., Yee, B. A. & Yeo, G. W. Evaluation of engineered CRISPR-cas-mediated systems for site-specific RNA editing. Cell Rep. 33, 108350 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • 103.

    Qu, L. et al. Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs. Nat. Biotechnol. 37, 1059–1069 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • 104.

    Cox, D. B. T. et al. RNA editing with CRISPR–Cas13. Science 358, 1019–1027 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 105.

    Rauch, S. et al. Programmable RNA-guided RNA effector proteins built from human parts. Cell 178, 122–134.e12 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 106.

    Abudayyeh, O. O. et al. A cytosine deaminase for programmable single-base RNA editing. Science 365, 382–386 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 107.

    Salzman, J. Circular RNA expression: its potential regulation and function. Trends Genet. 32, 309–316 (2016).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 108.

    Lasda, E. & Parker, R. Circular RNAs: diversity of form and function. RNA 20, 1829–1842 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 109.

    Akhter, R. Circular RNA and Alzheimer’s disease. Adv. Exp. Med. Biol. 1087, 239–243 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • 110.

    Altesha, M.-A., Ni, T., Khan, A., Liu, K. & Zheng, X. Circular RNA in cardiovascular disease. J. Cell Physiol. 234, 5588–5600 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • 111.

    Han, B., Chao, J. & Yao, H. Circular RNA and its mechanisms in disease: from the bench to the clinic. Pharmacol. Ther. 187, 31–44 (2018).

    CAS 
    PubMed 

    Google Scholar 

  • 112.

    Prats, A.-C. et al. Circular RNA, the key for translation. Int. J. Mol. Sci. 21, 8591 (2020).

    CAS 
    PubMed Central 

    Google Scholar 

  • 113.

    Legnini, I. et al. Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Mol. Cell 66, 22–37.e9 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 114.

    Pamudurti, N. R. et al. Translation of circRNAs. Mol. Cell 66, 9–21.e7 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 115.

    Litke, J. L. & Jaffrey, S. R. Highly efficient expression of circular RNA aptamers in cells using autocatalytic transcripts. Nat. Biotechnol. 37, 667–675 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 116.

    Wesselhoeft, R. A., Kowalski, P. S. & Anderson, D. G. Engineering circular RNA for potent and stable translation in eukaryotic cells. Nat. Commun. 9, 2629 (2018).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 117.

    Meganck, R. M. et al. Engineering highly efficient backsplicing and translation of synthetic circRNAs. Mol. Ther. Nucleic Acids 23, 821–834 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 118.

    Paige, J. S., Wu, K. Y. & Jaffrey, S. R. RNA mimics of green fluorescent protein. Science 333, 642–646 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 119.

    Rossbach, O. Artificial circular RNA sponges targeting microRNAs as a novel tool in molecular biology. Mol. Ther. Nucleic Acids 17, 452–454 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 120.

    Jost, I. et al. Functional sequestration of microRNA-122 from hepatitis C virus by circular RNA sponges. RNA Biol. 15, 1032–1039 (2018).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 121.

    Blight, K. J., McKeating, J. A. & Rice, C. M. Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication. J. Virol. 76, 13001–13014 (2002).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 122.

    Schreiner, S., Didio, A., Hung, L.-H. & Bindereif, A. Design and application of circular RNAs with protein-sponge function. Nucleic Acids Res. 48, 12326–12335 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 123.

    Li, X., Yang, L. & Chen, L.-L. The biogenesis, functions, and challenges of circular RNAs. Mol. Cell 71, 428–442 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 124.

    Delebecque, C. J., Lindner, A. B., Silver, P. A. & Aldaye, F. A. Organization of intracellular reactions with rationally designed RNA assemblies. Science 333, 470–474 (2011).

    CAS 
    PubMed 

    Google Scholar 

  • 125.

    Sachdeva, G., Garg, A., Godding, D., Way, J. C. & Silver, P. A. In vivo co-localization of enzymes on RNA scaffolds increases metabolic production in a geometrically dependent manner. Nucleic Acids Res. 42, 9493–9503 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 126.

    Shibata, T. et al. Protein-driven RNA nanostructured devices that function in vitro and control mammalian cell fate. Nat. Commun. 8, 540 (2017).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 127.

    WHO. WHO coronavirus (COVID-19) dashboard with vaccination data. World Health Organization https://covid19.who.int/info (2020).

  • 128.

    Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • 129.

    Corbett, K. S. et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature 586, 567–571 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 130.

    Slaoui, M. & Hepburn, M. Developing safe and effective covid vaccines — Operation Warp Speed’s strategy and approach. N. Engl. J. Med. 383, 1701–1703 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • 131.

    Bell, J. Moderna founder’s next big play in RNA raises $440M. BioPharma Dive https://www.biopharmadive.com/news/laronde-endless-rna-series-b-flagship-moderna/605740/ (2021).

  • 132.

    Bell, J. Venture capital pours more money into RNA medicines with the launch of Replicate. BioPharma Dive https://www.biopharmadive.com/news/replicate-launch-rna-ehlers-apple-tree/606210/ (2021).

  • 133.

    Al Idrus, A. Shape builds out RNA editing tech with a major $112M funding boost. FierceBiotech https://www.fiercebiotech.com/biotech/shape-therapeutics-reels-112m-to-spur-rna-editing-tech (2021).

  • 134.

    Baek, M. et al. Accurate prediction of protein structures and interactions using a three-track neural network. Science 373, 871–876 (2021).

    CAS 
    PubMed 

    Google Scholar 

  • 135.

    Senior, A. W. et al. Improved protein structure prediction using potentials from deep learning. Nature 577, 706–710 (2020).

    CAS 

    Google Scholar 

  • 136.

    Kuhlman, B. & Bradley, P. Advances in protein structure prediction and design. Nat. Rev. Mol. Cell Biol. 20, 681–697 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 137.

    Langan, R. A. et al. De novo design of bioactive protein switches. Nature 572, 205–210 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 138.

    Zhang, K. et al. Cryo-EM structure of a 40 kDa SAM-IV riboswitch RNA at 3.7 Å resolution. Nat. Commun. 10, 5511 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 139.

    Mustoe, A. M., Lama, N. N., Irving, P. S., Olson, S. W. & Weeks, K. M. RNA base-pairing complexity in living cells visualized by correlated chemical probing. Proc. Natl Acad. Sci. USA 116, 24574–24582 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 140.

    Yesselman, J. D. et al. Computational design of three-dimensional RNA structure and function. Nat. Nanotechnol. 14, 866–873 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 141.

    Watkins, A. M., Rangan, R. & Das, R. FARFAR2: improved de novo Rosetta prediction of complex global RNA folds. Structure 28, 963–976.e6 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 142.

    Townshend, R. J. L. et al. Geometric deep learning of RNA structure. Science 373, 1047–1051 (2021).

    CAS 
    PubMed 

    Google Scholar 

  • 143.

    Rosa, S. S., Prazeres, D. M. F., Azevedo, A. M. & Marques, M. P. C. mRNA vaccines manufacturing: challenges and bottlenecks. Vaccine 39, 2190–2200 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 144.

    Shi, H. et al. Bias in RNA-seq library preparation: current challenges and solutions. Biomed. Res. Int. 2021, 6647597 (2021).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 145.

    Yu, A.-M., Choi, Y. H. & Tu, M.-J. RNA drugs and RNA targets for small molecules: principles, progress, and challenges. Pharmacol. Rev. 72, 862–898 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 146.

    Schlick, T. & Pyle, A. M. Opportunities and challenges in RNA structural modeling and design. Biophysical J. 113, 225–234 (2017).

    CAS 

    Google Scholar 

  • 147.

    Potter, K., Cremona, N. & Wise, J. A. in Encyclopedia of Biological Chemistry 2nd edn (eds Lennarz, W. J. & Lane, M. D.) 59–64 (Academic, 2013).

  • 148.

    Wilkinson, M. E., Charenton, C. & Nagai, K. RNA splicing by the spliceosome. Annu. Rev. Biochem. 89, 359–388 (2020).

    CAS 
    PubMed 

    Google Scholar 

  • 149.

    Chen, L.-L. The biogenesis and emerging roles of circular RNAs. Nat. Rev. Mol. Cell Biol. 17, 205–211 (2016).

    CAS 
    PubMed 

    Google Scholar 

  • 150.

    Zhang, X. et al. Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway. Mol. Cancer 18, 20 (2019).

    PubMed 
    PubMed Central 

    Google Scholar 

  • 151.

    Cesana, M. et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147, 358–369 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • 152.

    Merkle, T. et al. Precise RNA editing by recruiting endogenous ADARs with antisense oligonucleotides. Nat. Biotechnol. 37, 133–138 (2019).

    CAS 
    PubMed 

    Google Scholar 

  • Source link