Issue 38, 2020

A bipedal DNA nanowalker fueled by catalytic assembly for imaging of base-excision repairing in living cells

Abstract

DNA nanowalkers moving progressively along a prescribed DNA track are useful tools in biosensing, molecular theranostics and biosynthesis. However, stochastic DNA nanowalkers that can perform in living cells have been largely unexplored. We report the development of a novel stochastic bipedal DNA walker that, for the first time, realizes direct intracellular base excision repair (BER) fluorescence activation imaging. In our design, the bipedal walker DNA was generated by BER-related human apurinic/apyrimidinic endonuclease 1 (APE1)-mediated cleavage of DNA sequences at an abasic site in the intracellular environment, and it autonomously travelled on spherical nucleic acid (SNA) surfaces via catalyzed hairpin assembly (CHA). Our nanomachine outperforms the conventional single leg-based DNA walker with an improved sensitivity, kinetics and walking steps. Moreover, in contrast to the single leg-based DNA walker, the bipedal DNA walker is capable of monitoring the fluorescence signal of reduced APE1 activity, thus indicating amplified intracellular imaging. This bipedal DNA-propelled DNA walker presents a simple and modular amplification mechanism for intracellular biomarkers of interest, providing an invaluable platform for low-abundance biomarker discovery leading to the accurate identification and effective treatment of cancers.

Graphical abstract: A bipedal DNA nanowalker fueled by catalytic assembly for imaging of base-excision repairing in living cells

Supplementary files

Article information

Article type
Edge Article
Submitted
04 7 2020
Accepted
13 8 2020
First published
14 8 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2020,11, 10361-10366

A bipedal DNA nanowalker fueled by catalytic assembly for imaging of base-excision repairing in living cells

M. Lv, J. Liu, R. Yu and J. Jiang, Chem. Sci., 2020, 11, 10361 DOI: 10.1039/D0SC03698F

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