Using DNA to Cross Membrane Barriers

Professor Stefan Howorka, University College London. Part of the physical seminar series

Semifluid membranes enclose biological cells and drug delivery vehicles. Yet, crossing the barrier enables the essential transport of molecular cargo. My talk presents synthetic transport channels made from DNA. Nucleic acids are easier to engineer than proteins of biological channels(1). The artificial DNA channels are composed of interlinked duplexes; attached lipid anchors hold the negatively charged structures in the membrane(2,3,4). DNA channels open and close in response to physical voltage stimuli like natural templates(3,4,5). One DNA version mimics ligand-gated channels(3) to help release control of drugs or build cell-like networks.

The artificial pores can furthermore be programmed into cytotoxic agents to kill cancer cells via limited membrane-rupturing(6), or create porous bionanoreactors with enclosed enzymatic activity(7). Other rationally designed DNA nanostructures extend the functional range and can control, for example, bilayer shape(8). In summary, DNA can –with the help of chemical modifications and rational design- replicate biological functions to open up new applications in nanobiotechnology and synthetic biology.

(1) Nat. Nanotechnol. 2017 12 619;
(2) Nano Lett. 2013 13 2351; Angew. Chem. Int. Ed. 2013 52 12069; ACS Nano 2018 in press
(3) Nat. Nanotechnol. 2016 11 152;
(4) ACS Nano 2015 9 1117;
(5) ACS Nano 2015 9 11209; Nat. Commun. 2017 8 14784;
(6) Angew. Chem. Int. Ed. 2014 53 12466; Nat. Chem. 2014 7 17;
(7) Angew. Chem. Int. Ed. 2016 55 11106;
(8) Science 2016 352 890; Nat. Chem. 2017 9 611; Nat. Commun. 2018 9 in press;