Design and Synthesis of DNA Origami Nanostructures to Control TNF Receptor Activation

Göktuğ Aba, Ferenc A Scheeren, Thomas H Sharp*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter in a book

1 Citation (Scopus)

Abstract

Clustering of type II tumor necrosis factor (TNF) receptors (TNFRs) is essential for their activation, yet currently available drugs fail to activate signaling. Some strategies aim to cluster TNFR by using multivalent streptavidin or scaffolds based on dextran or graphene. However, these strategies do not allow for control of the valency or spatial organization of the ligands, and consequently control of the TNFR activation is not optimal. DNA origami nanostructures allow nanometer-precise control of the spatial organization of molecules and complexes, with defined spacing, number and valency. Here, we demonstrate the design and characterization of a DNA origami nanostructure that can be decorated with engineered single-chain TNF-related apoptosis-inducing ligand (SC-TRAIL) complexes, which show increased cell killing compared to SC-TRAIL alone on Jurkat cells. The information in this chapter can be used as a basis to decorate DNA origami nanostructures with various proteins, complexes, or other biomolecules.

Original languageEnglish
Title of host publicationImaging Cell Signalling
PublisherHumana Press
Pages35-53
Number of pages19
ISBN (Electronic)9781071638347
ISBN (Print)9781071638330
DOIs
Publication statusPublished - 7 May 2024

Publication series

NameMethods in Molecular Biology
Volume2800
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature 2024.

Keywords

  • Nanostructures/chemistry
  • Humans
  • Jurkat Cells
  • DNA/chemistry
  • TNF-Related Apoptosis-Inducing Ligand/chemistry
  • Receptors, Tumor Necrosis Factor/metabolism
  • Nanotechnology/methods
  • Nucleic Acid Conformation

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