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

Göktuğ Aba, Ferenc A Scheeren, Thomas H Sharp

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

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
Pages35-53
Number of pages19
Volume2800
DOIs
Publication statusPublished - 7 May 2024

Publication series

NameMethods in molecular biology (Clifton, N.J.)
PublisherHumana Press
ISSN (Print)1064-3745

Bibliographical note

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

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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