Therapeutic and Diagnostic Applications of Rapidly Reversible Aptamers
Bruce Sullenger, Ruwan Gunaratne, James Frederiksen, Kady-Ann Steen-Burrell, Bethany Gray
Duke Translational Research Institute, Department of Surgery, Duke University, Durham, North Carolina, USA
Clinical evaluation of our factor IXa aptamer in two thousand patients undergoing angioplasty has demonstrated that aptamers can rapidly and potently inhibit their target proteins in patients and that antidote molecules can rapidly reverse such activity in the minute time frame. These observations suggest that aptamers may represent very useful molecules to control or monitor biochemical processes in humans in real time. To begin to explore this potential further, we have started to evaluate the utility of antidote-mediated control of aptamers for a variety of other therapeutic and diagnostic applications. We will describe our recent progress developing a rapidly controllable factor Xa anticoagulant aptamer to effectively and reversible control blood coagulation during cardiopulmonary bypass surgery, a rapidly reversible thrombin aptamer for imaging blood clots in real time and rapidly reversible tumor targeting aptamer-chemotherapeutic drug conjugates to limit side effects of chemotherapeutic agents. Collectively these preclinical studies lead us to believe that rapidly controllable aptamers represent valuable therapeutic and diagnostic agents to monitor and control biological processes in real time.