Thrombosis is a major cause of critical cardiovascular disorders such as heart attacks and strokes, leading to severe and often fatal outcomes. Current treatments primarily involve aggressive antithrombotic medications that require high systemic concentrations and carry a high risk of bleeding, often being fatal. This side effect limits the usage of antithrombotic drugs as preventative medication, especially in patients at higher risk bleeding. Our team has previously engineered a novel antibody, scFvAP that selectively targets activated platelets and prevents clot formation. We have shown that scFvAP inhibits thrombosis and provides cardioprotection after a heart attack, without increasing the risk of bleeding. Therefore, scFvAP is a safe prophylactic option. However, its small size leads to rapid clearance from the body, necessitating frequent administrations every 4 h, complicating clinical use. To overcome this limitation, we propose an innovative mRNA-therapeutic approach using lipid-based nanoparticles (LNPs) enhancing the delivery and expression of scFvAP. This strategy aims to extend the therapeutic efficacy and reduce dosing frequency. Our preliminary experiments have shown that encapsulating mRNA within LNPs improves mRNA stability and enhances transfection efficiency by over a week. In this proposal, we plan to further evaluate the expression, efficacy, longevity, and safety of this system in vivo. We anticipate that a single injection of scFvAP mRNA-LNPs could sustain therapeutic levels of the antibody for an extended period, potentially opening up novel preventive treatment for thrombosis thereby preventing venous thrombosis, pulmonary embolism, heart attacks, and strokes. By reducing the need for frequent doses and continuous monitoring, our approach could decrease healthcare burdens of patients at high risk of thrombosis, and emerge as a feasible option for broad clinical application. Additionally, the underlying principles of this mRNA and LNP methodology could be adapted to treat a wider array of medical conditions, significantly broadening its impact across various fields of medicine.
Last updated31 October 2025