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| Status |
Public on Dec 28, 2023 |
| Title |
Coagulation Factor XIII-Binding Aptamers as Bivalent Ligands Targeting Fibrin and Activated Platelets in the Thrombus |
| Organism |
synthetic construct |
| Experiment type |
Other
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| Summary |
Thromboembolic diseases are commonly associated with thrombus-induced ischemia and tissue damage; identification of the location of the thrombus, or thrombus-targeting, may facilitate diagnosis and target therapy. We hypothesized that aptamers with high affinity and specificity for coagulation factor XIII (FXIII) can serve as thrombus-targeting probes. With systematic evolution of ligands by exponential enrichment technology and semi-activated FXIII (FXIII’) as the target, guanine-rich FXIII’-binding aptamers (FAs; 76 nt) were selected from a library of single-stranded DNA. Next generation sequencing identified FAs with the highest frequency; bio-layer interferometry revealed a dissociation constant (Kd) from 0.7 to 2.5 nM. Truncation with preservation of a conserved region based on entropy analysis resulted in three truncated FAs (FATs; 41-47 nt) that exhibited 4-fold signal in binding to activated vs. resting platelets, as determined by flowcytometry. In addition, FAT2 exhibited up to 4.2-fold binding of that from scrambled ssDNA to platelet/fibrin clot or whole blood clot in vitro, suggesting binding to both activated plateltes and fibrin. FAT2 also exhibited targeting effects in a microcirculatory thrombosis model in mice. Nevertheless, FATs induced no effect on blood coagulation, as determined by thromboelastometry. In conclusion, FXIII-binding aptamers are potentially amenable to thrombus targeting in theranostic application of thromboembolic diseases.
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| Overall design |
To development FXIII-targeting aptamer for thrombus imaging
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| Contributor(s) |
Cheng K, Tseng C, Tzeng Y, Fu W, Liu H, Chen G, Liao H, Ma Y |
| Citation missing |
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| Submission date |
Dec 28, 2020 |
| Last update date |
Dec 28, 2023 |
| Contact name |
Kai Wen Cheng |
| E-mail(s) |
kevin19921024@gmail.com
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| Organization name |
Chang Gung University
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| Department |
Physiology and Pharmacology
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| Lab |
Yunn Hwa Ma lab
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| Street address |
259 Wen-Hwa 1st Road, Kwei-Shan
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| City |
Taoyuan |
| ZIP/Postal code |
333 |
| Country |
Taiwan |
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| Platforms (1) |
| GPL19424 |
Illumina NextSeq 500 (synthetic construct) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA688234 |
| SRA |
SRP299475 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE163934_RAW.tar |
40.0 Kb |
(http)(custom) |
TAR (of XLSX) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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