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Designing a Bio-responsive Robot from DNA Origami
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Innate Immune Stimulation Using 3D Wireframe DNA Origami.

Rebecca R Du1, Edward Cedrone2, Anna Romanov1,3

  • 1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts02139, United States.

ACS Nano
|December 2, 2022
PubMed
Summary
This summary is machine-generated.

Three-dimensional DNA origami can be designed to control immune responses. Modifying their structure with specific DNA sequences activates immune pathways, offering potential for new therapies.

Keywords:
3D wireframe DNA origamiCpGTLR9immunomodulationimmunostimulationmultivalency

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Area of Science:

  • Nanotechnology
  • Immunology
  • Biochemistry

Background:

  • Three-dimensional (3D) wireframe DNA origami possess programmable features for potential prophylactic and therapeutic uses.
  • The immunological properties of 3D DNA origami, influenced by shape and CpG content, are not well understood.

Purpose of the Study:

  • To investigate the immunostimulatory properties of 3D wireframe DNA origami on the Toll-like receptor 9 (TLR9) pathway.
  • To identify design parameters for modulating immune activation in DNA origami for therapeutic applications.

Main Methods:

  • Utilized reporter cell lines and primary immune cells to assess TLR9 pathway activation by 3D wireframe DNA origami.
  • Examined the impact of CpG dinucleotide content, multivalent display, and spatial organization on immune response.
  • Measured Type I and Type III interferon production in peripheral blood mononuclear cells.

Main Results:

  • Bare 3D polyhedral wireframe DNA origami induced minimal TLR9 activation, even with internal CpG dinucleotides.
  • Displaying multivalent CpG-containing single-stranded DNA (ssDNA) oligos on DNA origami triggered robust TLR9 activation.
  • CpG copy number and spatial arrangement significantly influenced TLR9 signaling magnitude.
  • CpGs attached to NANP did not require phosphorothioate stabilization for signaling.

Conclusions:

  • 3D wireframe DNA origami can be designed to controllably modulate immune pathway activation.
  • Strategic display of CpG motifs is crucial for potent TLR9 activation via DNA origami.
  • These findings provide key design principles for developing immune-modulating DNA origami therapeutics.