Innate Immune Stimulation Using 3D Wireframe DNA Origami
Name
2022.07.08.499376v1.full.pdf
Description
Submitted version
Size
1.55 MB
Format
Adobe PDF
Checksum (MD5)
1fa73d310b44192e7d00d2bef3bd3ac7
Author(s)
Du, Rebecca R
Cedrone, Edward
Romanov, Anna
Falkovich, Reuven
Dobrovolskaia, Marina A
Bathe, Mark
Date Issued
December 27, 2022
Journal
ACS Nano
Publisher
American Chemical Society (ACS)
Citation
Du, Rebecca R, Cedrone, Edward, Romanov, Anna, Falkovich, Reuven, Dobrovolskaia, Marina A et al. 2022. "Innate Immune Stimulation Using 3D Wireframe DNA Origami." ACS Nano, 16 (12).
Version
Original manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1021/acsnano.2c06275
