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Precision immunomodulation with synthetic nucleic acid technologies

Abstract

DNA and RNA of both natural and synthetic origin can elicit strong immune responses in higher organisms. Computer-aided design in conjunction with high-throughput sequencing has improved our ability to build tuneable synthetic DNA and RNA architectures with high structural and functional precision. The natural biological roles of nucleic acids endow these synthetic assemblies with the ability to specifically engage cellular components. This makes DNA and RNA particularly powerful materials with which to probe or programme immune cells. In this Perspective, we discuss the potential of designer nucleic acid assemblies to control and modulate the immune response for biomedical applications.

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Fig. 1: Synthetic nucleic acid technologies for quantitative immunology.
Fig. 2: Strategies for immunomodulation.
Fig. 3: Established receptors and cytokine targets for immunomodulation.
Fig. 4: Hybrid strategies for immunomodulation.
Fig. 5: Synthetic RNA circuits in immune cells.

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Acknowledgements

The authors thank J. Kuriyan (University of California, Berkeley) and V. Kumar (The University of Chicago) for comments and suggestions. This work was supported by a research grant from the University of Pennsylvania Orphan Disease Center in partnership with the Andrew Coppola Foundation, the University of Chicago Women’s Board; a Pilot and Feasibility award from National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Center grant no. P30DK42086 to the University of Chicago Digestive Diseases Research Core Center; the Chicago Biomedical Consortium, with support from the Searle Funds at The Chicago Community Trust, C-084; and University of Chicago start-up funds to Y.K. Y.K. is a Brain Research Foundation Fellow. Our sincere apologies to those colleagues whose work could not be included owing to space limitations.

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M.S.J., A.T.V. and Y.K. developed the concepts and framework of the review and translated these into figures and text.

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Correspondence to Yamuna Krishnan.

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Jani, M.S., Veetil, A.T. & Krishnan, Y. Precision immunomodulation with synthetic nucleic acid technologies. Nat Rev Mater 4, 451–458 (2019). https://doi.org/10.1038/s41578-019-0105-4

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