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Generation and characterization of aptamers targeting factor XIa
R S Woodruff1, I Ivanov2, I M Verhamme2
1Department of Surgery, Duke University Medical Center, Durham, NC, United States; University Program in Genetics and Genomics, Duke University, Durham, NC, United States.
Thrombosis Research
|June 24, 2017
Summary
RNA aptamers were developed to inhibit factor XIa (FXIa), a key target for preventing blood clots. These aptamers show potential as novel therapeutic inhibitors for thrombotic disorders.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Factor XIa (FXIa) is a plasma protease of significant interest for developing antithrombotic therapies.
- Targeting FXIa offers a potential strategy for managing thrombotic disorders.
Purpose of the Study:
- To isolate and characterize RNA aptamers that inhibit the catalytic activity of FXIa.
- To explore the potential of aptamers as novel therapeutic agents against FXIa.
Main Methods:
- Employed systematic evolution of ligands by exponential enrichment (SELEX), a directed evolution technique.
- Utilized a solution-based approach to identify RNA aptamers targeting the FXIa catalytic domain.
Main Results:
- Identified two RNA aptamers, 11.16 and 12.7, that bind to specific sites on the FXIa catalytic domain.
- Demonstrated that these aptamers act as non-competitive inhibitors of FXIa activity, including its role in factor IX activation.
- Aptamer 12.7 significantly extended plasma clotting time (aPTT), indicating anticoagulant properties.
Conclusions:
- Systematic evolution of ligands by exponential enrichment (SELEX) is effective for generating novel FXIa inhibitors.
- RNA aptamers can effectively bind to distinct sites on FXIa and inhibit its activity.
- These aptamer-based inhibitors show promise for therapeutic development in treating thrombotic conditions.
