Publications [#99845] of Bruce A Sullenger

Papers Published

1. CP Rusconi, JD Roberts, GA Pitoc, SM Nimjee, RR White, G Quick Jr, E Scardino, WP Fay, BA Sullenger, Antidote-mediated control of an anticoagulant aptamer in vivo., Nature biotechnology, vol. 22 no. 11 (November, 2004), pp. 1423-8, ISSN 1087-0156 [doi]
   (last updated on 2013/05/16)

   Abstract:
   Patient safety and treatment outcome could be improved if physicians could rapidly control the activity of therapeutic agents in their patients. Antidote control is the safest way to regulate drug activity, because unlike rapidly clearing drugs, control of the drug activity is independent of underlying patient physiology and co-morbidities. Until recently, however, there was no general method to discover antidote-controlled drugs. Here we demonstrate that the activity and side effects of a specific class of drugs, called aptamers, can be controlled by matched antidotes in vivo. The drug, an anticoagulant aptamer, systemically induces anticoagulation in pigs and inhibits thrombosis in murine models. The antidote rapidly reverses anticoagulation engendered by the drug, and prevents drug-induced bleeding in surgically challenged animals. These results demonstrate that rationally designed drug-antidote pairs can be generated to provide control over drug activities in animals.

   Keywords:
   Animals • Anticoagulants • Antidotes • Blood Coagulation • Blood Coagulation Tests • Carotid Artery Thrombosis • Drug Interactions • Drug Therapy, Combination • Hemorrhage • Mice • Oligonucleotides • Swine • Treatment Outcome • administration & dosage* • adverse effects* • chemically induced* • drug effects* • drug therapy • prevention & control*