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Genetically Encoded, Functional Single-Strand RNA Origami: Anticoagulant.
Abhichart Krissanaprasit1, Carson Key1, Michael Fergione1
1Department of Materials Science and Engineering, College of Engineering, North Carolina State University, Raleigh, NC, 27695, USA.
Advanced Materials (Deerfield Beach, Fla.)
|April 12, 2019
Summary
New RNA origami structures with multiple aptamers show significantly improved anticoagulant activity, potentially overcoming limitations of earlier nucleic acid anticoagulants for clinical use.
Area of Science:
- Biochemistry
- Molecular Biology
- Biotechnology
Background:
- Nucleic acid aptamers targeting thrombin exhibit anticoagulant properties.
- Clinical application is hindered by rapid renal clearance and short half-life.
Purpose of the Study:
- To develop novel RNA origami constructs with enhanced anticoagulant activity.
- To address limitations of existing nucleic acid anticoagulants for therapeutic use.
Main Methods:
- Designing and producing RNA origami molecules with multiple thrombin-binding aptamers via in vitro transcription.
- Incorporating 2'-fluoro-modified nucleotides to enhance nuclease resistance and stability.
- Evaluating thrombin binding, stability in plasma and RNase A, and anticoagulant activity.
Main Results:
- RNA origami demonstrated significantly improved anticoagulant activity (sevenfold greater than free aptamer).
- Constructs showed high stability in human plasma and against RNase A, outperforming DNA.
- Anticoagulant effect was reversible with DNA antidotes and stable for over 3 months.
Conclusions:
- RNA origami technology offers a promising platform for developing effective and stable nucleic acid anticoagulants.
- These constructs represent a potential advancement for safer anticoagulation therapies, including surgical applications.
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