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A Biomimetic DNA‐Based Membrane Gate for Protein‐Controlled Transport of Cytotoxic Drugs
Author(s) -
Lanphere Conor,
Arnott Patrick M.,
Jones Sioned Fôn,
Korlova Katarina,
Howorka Stefan
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202011583
Subject(s) - nanopore , aptamer , dna , nanotechnology , biophysics , dna nanotechnology , membrane , synthetic biology , biosensor , chemistry , nanobiotechnology , materials science , biology , computational biology , biochemistry , nanoparticle , microbiology and biotechnology
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.