Poly-Adenine-Based Spherical Nucleic Acids for Efficient Live-Cell MicroRNA Capture

Kai Jiao; Qinglong Yan; Linjie Guo; Zhibei Qu; Shuting Cao; Xiaoliang Chen; Qian Li; Ying Zhu; Jiang Li; Lihua Wang; Chunhai Fan; Fei Wang

doi:10.1002/anie.202017039

Poly-Adenine-Based Spherical Nucleic Acids for Efficient Live-Cell MicroRNA Capture

Angew Chem Int Ed Engl. 2021 Jun 21;60(26):14438-14445. doi: 10.1002/anie.202017039. Epub 2021 May 24.

Authors

Kai Jiao^{1

2}, Qinglong Yan^{1

2}, Linjie Guo^{1

2}, Zhibei Qu³, Shuting Cao^{1

2}, Xiaoliang Chen³, Qian Li³, Ying Zhu^{1

4}, Jiang Li^{1

3

4}, Lihua Wang⁴, Chunhai Fan^{3

5}, Fei Wang³

Affiliations

¹ Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.
² University of Chinese Academy of Sciences, Beijing, 100049, China.
³ School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
⁴ Bioimaging Center, Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, The Interdisciplinary Research Center, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China.
⁵ Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acids Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

PMID: 33851770
DOI: 10.1002/anie.202017039

Abstract

Direct delivery of exogenous non-coding nucleic acids into living cells has attracted intense interest in biological applications. However, the cell entry efficiency and target capture ability remain to be improved. Herein, we report a method for compartmenting the nucleic acids on the surface of poly-adenine-based spherical nucleic acids (polyA-SNAs) for efficient capture of oncogenic microRNAs (miRNAs) in living cells. We find that polyA-SNAs exhibit high cell entry efficiency, which is insensitive to the configuration of the anti-miRNA sequences. By programming the length of polyAs, we precisely engineered the spatial configuration of the anti-miRNA sequences in polyA-SNAs. Compartmentalized polyA-SNAs bind to miRNAs with improved capture ability as compared to densely compacted SNAs. We further demonstrate that polyA-SNAs serve as high-efficacy miRNA sponges for capturing oncogenic miRNAs both in living cells and in mice. The efficient inhibition of miRNAs results in significant suppression of tumor growth.

Keywords: RNA delivery; RNA recognition; microRNA; nanoparticles; spherical nucleic acids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

HEK293 Cells
Humans
MicroRNAs / chemistry
MicroRNAs / isolation & purification*
Nucleic Acids / chemistry*
Particle Size
Poly A / chemistry*

Substances

MicroRNAs
Nucleic Acids
polyadenine
Poly A