Scientists have developed a new method to control blood clotting during medical procedures safely. Blood thinners, which prevent dangerous clots, can be tricky because stopping them quickly and safely can be difficult. A cross-departmental team of researchers includes Professor Thom LaBean and Dr. Abhichart Krissanaprasit focuses on a special type of blood thinner called HEX01, which is made from a unique structure of RNA (a molecule similar to DNA). What makes this discovery exciting is a fast-acting antidote called HEX02, which can immediately stop the effects of HEX01.
In lab tests, HEX01 was found to be very effective at preventing blood clots both in test tubes and in living organisms. The new antidote, HEX02, was able to reverse the blood-thinning effect in less than 30 seconds when tested in human plasma. When used in a mouse model, the antidote worked effectively to stop bleeding after a liver injury.
Researchers also studied how HEX01 moves through the body, finding that it mainly gathers in the liver with smaller amounts in the kidneys. Importantly, the study showed that HEX01 and HEX02 did not harm cells or cause unwanted reactions in the body, making them safe in early tests.
This new blood thinner and its antidote could lead to better and safer ways to manage blood clotting during surgeries or other medical procedures. While more research is needed, the early results are promising for future drug development.
Note to Editors: The study abstract follows.
“A functional RNA-origami as direct thrombin inhibitor with fast-acting and specific single-molecule reversal agents in vivo model”
Authors: Abhichart Krissanaprasit, Thomas H. LaBean and Katherine Meinhold, North Carolina State University Materials Science and Engineering; Emily Mihalko, Aryssa Simpson, Jennifer Sollinger, Sanika Pandit and Ashley C. Brown, North Carolina State University Joint Department of Biomedical Engineering; Daniel M. Dupont and Jørgen Kjems, Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus University, Denmark
Published: July 3, Molecular Therapy
Abstract: Injectable anticoagulants are widely used in medical procedures to prevent unwanted blood clotting. However, many lack safe, effective reversal agents. Here, we present new data on a previously described RNA origami-based, direct thrombin inhibitor (HEX01). We describe a new, fast-acting, specific, single-molecule reversal agent (antidote) and present in vivo data for the first time, including efficacy, reversibility, preliminary safety, and initial biodistribution studies. HEX01 contains multiple thrombin-binding aptamers appended on an RNA origami. It exhibits excellent anticoagulation activity in vitro and in vivo. The new single-molecule, DNA antidote (HEX02) reverses anticoagulation activity of HEX01 in human plasma within 30 s in vitro and functions effectively in a murine liver laceration model. Biodistribution studies of HEX01 in whole mice using ex vivo imaging show accumulation mainly in the liver over 24 h and with 10-fold lower concentrations in the kidneys. Additionally, we show that the HEX01/HEX02 system is non-cytotoxic to epithelial cell lines and non-hemolytic in vitro. Furthermore, we found no serum cytokine response to HEX01/HEX02 in a murine model. HEX01 and HEX02 represent a safe and effective coagulation control system with a fast-acting, specific reversal agent showing promise for potential drug development.