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A Biomimetic DNA‐Based Membrane Gate for Protein‐Controlled Transport of Cytotoxic Drugs

Lanphere, C; Arnott, PM; Jones, SF; Korlova, K; Howorka, S; (2021) A Biomimetic DNA‐Based Membrane Gate for Protein‐Controlled Transport of Cytotoxic Drugs. Angewandte Chemie , 133 (4) pp. 1931-1936. 10.1002/ange.202011583. Green open access

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Abstract

Chemistry is ideally placed to replicate biomolecular structures with tuneable building materials. Of particular interest are molecular nanopores, which transport cargo across membranes, as in DNA sequencing. Advanced nanopores control transport in response to triggers, but this cannot be easily replicated with biogenic proteins. Here we use DNA nanotechnology to build a synthetic molecular gate that opens in response to a specific protein. The gate self-assembles from six DNA strands to form a bilayer-spanning pore, and a lid strand comprising a protein-binding DNA aptamer to block the channel entrance. Addition of the trigger protein, thrombin, selectively opens the gate and enables a 330-fold increase inw the transport rate of small-molecule cargo. The molecular gate incorporates in delivery vesicles to controllably release enclosed cytotoxic drugs and kill eukaryotic cells. The generically designed gate may be applied in biomedicine, biosensing or for building synthetic cells.

Type: Article
Title: A Biomimetic DNA‐Based Membrane Gate for Protein‐Controlled Transport of Cytotoxic Drugs
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/ange.202011583
Publisher version: https://doi.org/10.1002/ange.202011583
Language: English
Additional information: © 2020 The Authors. Published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: aptamers, biosensors, DNA structures, membrane, nanopores
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10116141
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