Sprecher
Beschreibung
Antigen-triggered Activation of a DNA Origami Nanopore
D. Putz and H. Dietz
Laboratory for Biomolecular Nanotechnology, School of Natural Sciences, Technical University of Munich, Germany
Email: dominik.putz@tum.de
Fabricating nanostructures capable of reacting to physiological stimuli by dynamic reconfiguration is of great interest when considering new diagnostics and therapeutics. We envision designing nanopores made of DNA, transitioning between an inactive and active state in response to the presence of specific antigens. To this end, we use programmable triangular building blocks constructed from DNA, assembling with high yield into shell objects composed of 20 individual triangles [1]. The triangles are extended by a potential pore-forming moiety and display membrane anchoring units. When assembled into the DNA origami shell, the pore protrusions point into the shell’s interior and are, therefore, hidden, meaning that the nanopores are inactive. IgG antibodies are used as structural elements to kinetically trap the DNA origami shell in a metastable state to control the nanopore's activity and trigger the shell system's disassembly once the corresponding antigen is present [2]. The soluble antigens displace the IgGs from the shells and cause disassembly into the individual monomers, thereby transferring the nanopores into an active state. We have designed and produced triangular building blocks equipped with a potential pore-forming moiety and characterized the structures using negative-stain transmission electron microscopy and cryo-electron microscopy. We demonstrate the disassembly of DNA origami shells only in the presence of the corresponding antigen, which would activate the individual nanopores. We aim to investigate the pore-forming capability of the individual triangles in dye influx/efflux studies on vesicles.
References:
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C. Sigl, E. M. Willner, W. Engelen, et al., Programmable icosahedral shell system for virus trapping, Nat. Mater., 2021, 20, 1281-1289.
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W. Engelen, C. Sigl, K. Kadletz, E. M. Willner, H. Dietz, Antigen-Triggered Logic-Gating of DNA Nanodevices, J. Am. Chem. Soc., 2021, 143, 21630-21636.