RNA aptamers for thrombi imaging
Thrombosis (blood clots within blood vessels) is a major underlying factor in many cardiovascular diseases and a major source for complications following hospital stays and surgeries. Venous thrombosis occurs in approximately 1 per 1000 annually in adult populations. Deep vein thrombosis has over 200,000 US cases a year, while pulmonary embolism occurs in more than 200,000 US cases per year. The ability to quickly detect and monitor thrombi (blood clot) formation could improve diagnosis and treatment of clotting-related diseases, as the responsiveness of the blood clots to treatment decreases with age of the clot.
Molecular imaging is currently used to detect and monitor blood clots. Current techniques use ultrasound or peptides, small molecules or nanoparticles that target either coagulation components of the blood clots or enzymatic activity that is upregulated during clot formation. These methods require knowing where the clot might be, and may only provide indirect evidence of a clot, such as vessel wall thickening, or obstruction of blood flow. There is an unmet need for image techniques targeting specific components of blood clots as well as reversible imaging techniques that allow medical professionals to distinguish between types and age of the blood clots, which is relevant for the treatment and detection of blood clots.
This invention uses aptamers (oligonucleotide sequences) to image clots. The strength of using aptamers to image blood clots is that they can be generated against any target molecule, by screening large libraries of aptamers for binding to the target. This allows for customization to specific proteins present in the blood clot. This specificity allows for rapid detection and treatment of the blood clots. Aptamer imaging may also be used to detect the role of new proteins that play a role in blood clots, which may be used to identify new targets for blood clot treatment and therapy. Because all oligonucleotide sequences have a complementing sequence, these aptamers are reversible; their function can be rapidly reversed or neutralized. This allows for monitoring of the progression of blood clots, and for distinguishing between clots.
- This technology allows for the generation of aptamers that bind to specific components on the blood clot, such as thrombin.
- These aptamers are reversible, allowing for sequential and progressive monitoring of clot formation.
- Has the potential to be used as a diagnostic tool for blood clots as well as other thrombogenic diseases such as cancer.
- This tool may further advance our understanding of the role of thrombin in vivo as well as identify new genes for potential targets in blood clot therapies