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Evolution of a highly functional circular DNA aptamer in serum
- Source :
- Nucleic Acids Research
- Publication Year :
- 2020
- Publisher :
- Oxford University Press, 2020.
-
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.
- Subjects :
- Guanine
AcademicSubjects/SCI00010
Aptamer
Plasma protein binding
Circular DNA
Biology
010402 general chemistry
G-quadruplex
01 natural sciences
03 medical and health sciences
chemistry.chemical_compound
Thrombin
Chemical Biology and Nucleic Acid Chemistry
Genetics
medicine
Humans
030304 developmental biology
0303 health sciences
Aptamers, Nucleotide
0104 chemical sciences
Dissociation constant
G-Quadruplexes
chemistry
Biophysics
DNA, Circular
DNA
medicine.drug
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 13624962 and 03051048
- Volume :
- 48
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....528e6d4a6586505782868240912d729e