Evolution of a highly functional circular DNA aptamer in serum

Yu Mao, Jimmy Gu, Dingran Chang, Lei Wang, Lili Yao, Qihui Ma, Zhaofeng Luo, Hao Qu, Yingfu Li*, Lei Zheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Circular DNA aptamers are powerful candidates for therapeutic applications given their dramatically enhanced biostability. Herein we report the first effort to evolve circular DNA aptamers that bind a human protein directly in serum, a complex biofluid. Targeting human thrombin, this strategy has led to the discovery of a circular aptamer, named CTBA4T-B1, that exhibits very high binding affinity (with a dissociation constant of 19 pM), excellent anticoagulation activity (with the half maximal inhibitory concentration of 90 pM) and high stability (with a half-life of 8 h) in human serum, highlighting the advantage of performing aptamer selection directly in the environment where the application is intended. CTBA4T-B1 is predicted to adopt a unique structural fold with a central two-tiered guanine quadruplex capped by two long stem-loops. This structural arrangement differs from all known thrombin binding linear DNA aptamers, demonstrating the added advantage of evolving aptamers fromcircular DNA libraries. The method described here permits the derivation of circular DNA aptamers directly in biological fluids and could potentially be adapted to generate other types of aptamers for therapeutic applications.

Original languageEnglish (US)
Pages (from-to)10680-10690
Number of pages11
JournalNucleic acids research
Volume48
Issue number19
DOIs
StatePublished - 2020

ASJC Scopus subject areas

  • Genetics

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