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 from circular 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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Mao Y,Gu J,Chang D,Wang L,Yao L,Ma Q,Luo Z,Qu H,Li Y,Zheng Ldoi
10.1093/nar/gkaa800subject
Has Abstractpub_date
2020-11-04 00:00:00pages
10680-10690issue
19eissn
0305-1048issn
1362-4962pii
5918318journal_volume
48pub_type
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