AI Article Synopsis
- Clustering of type II TNF receptors (TNFRs) is crucial for their activation, but existing drugs do not effectively trigger signaling.
- Strategies like using multivalent streptavidin or dextran scaffolds aim to cluster TNFRs, but they lack control over the arrangement and number of ligands, limiting activation.
- DNA origami nanostructures provide precise control over the spatial organization and valency of molecules, enabling the design of enhanced TNF-related apoptosis-inducing ligand (SC-TRAIL) complexes that improve cell killing in Jurkat cells, with potential applications for decorating DNA origami with various biomolecules.
Article 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.
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| http://dx.doi.org/10.1007/978-1-0716-3834-7_4 | DOI Listing |
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