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Designing DNA nanodevices for compatibility with the immune system of higher organisms

Abstract

DNA is proving to be a powerful scaffold to construct molecularly precise designer DNA devices. Recent trends reveal their ever-increasing deployment within living systems as delivery devices that not only probe but also program and re-program a cell, or even whole organisms. Given that DNA is highly immunogenic, we outline the molecular, cellular and organismal response pathways that designer nucleic acid nanodevices are likely to elicit in living systems. We address safety issues applicable when such designer DNA nanodevices interact with the immune system. In light of this, we discuss possible molecular programming strategies that could be integrated with such designer nucleic acid scaffolds to either evade or stimulate the host response with a view to optimizing and widening their applications in higher organisms.

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Figure 1: DNA and its various nanostructured forms.
Figure 2: Natural mechanisms to detect and dispose of foreign DNA by host cells.
Figure 3: Targeting and delivery of DNA nanostructures in vivo.
Figure 4: Strategies to tune stability of designer DNA nanodevices to tailor host immune responses.

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Acknowledgements

A.R.S. acknowledges funds from the Royal Society (RG130811), the Wellcome Trust and Imperial College London start-up funds. Y.K. acknowledges the Wellcome-Trust DBT India Alliance (500095/Z/09/Z), HFSP Organisation (RGP0029/2014) and the University of Chicago start-up funds. The authors are grateful to A. Turberfield and J. Bath for high-resolution versions of Fig. 4(i). We appreciate feedback from numerous colleagues, and sincerely apologize to those authors whose work could not be included due to space limitations. In memory of our inspirational colleague, the late Professor Obaid Siddiqi.

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Correspondence to Avinash R. Shenoy or Yamuna Krishnan.

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Surana, S., Shenoy, A. & Krishnan, Y. Designing DNA nanodevices for compatibility with the immune system of higher organisms. Nature Nanotech 10, 741–747 (2015). https://doi.org/10.1038/nnano.2015.180

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