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Innate Immune Stimulation Using 3D Wireframe DNA Origami

  1. Author:
    Du, Rebecca R
    Cedrone,Edward
    Romanov, Anna [ORCID]
    Falkovich, Reuven
    Dobrovolskaia,Marina [ORCID]
    Bathe, Mark [ORCID]

  2. Author Address

    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States., Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, United States., Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.,
    1. Year: 2022
    2. Date: Dec 02
    3. Epub Date: 2022 12 02
  2. Journal: ACS Nano
  4. Type of Article: Article
  1. Abstract:

    Three-dimensional wireframe DNA origami have programmable structural and sequence features that render them potentially suitable for prophylactic and therapeutic applications. However, their innate immunological properties, which stem from parameters including geometric shape and cytosine-phosphate-guanine dinucleotide (CpG) content, remain largely unknown. Here, we investigate the immunostimulatory properties of 3D wireframe DNA origami on the TLR9 pathway using both reporter cell lines and primary immune cells. Our results suggest that bare 3D polyhedral wireframe DNA origami induce minimal TLR9 activation despite the presence of numerous internal CpG dinucleotides. However, when displaying multivalent CpG-containing ssDNA oligos, wireframe DNA origami induce robust TLR9 pathway activation, along with enhancement of downstream immune response as evidenced by increases in Type I and Type III interferon (IFN) production in peripheral blood mononuclear cells. Further, we find that CpG copy number and spatial organization each contribute to the magnitude of TLR9 signaling and that NANP-attached CpGs do not require phosphorothioate stabilization to elicit signaling. These results suggest key design parameters for wireframe DNA origami that can be programmed to modulate immune pathway activation controllably for prophylactic and therapeutic applications.

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External Sources

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  2. DOI: 10.1021/acsnano.2c06275
  3. PMID: 36459697

Library Notes

  1. Fiscal Year: FY2022-2023
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