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Bruce Sullenger

Professor and Director Duke Translational Research Institute
Research Interest: 
Molecular structure
Research Summary: 
Inventing and developing nucleic acid based therapies for the treatment of cardiovascular diseases and cancer.
Research Description: 

Dr. Sullenger has performed biochemical and translational research to develop nucleic acid-based therapeutics for more than two decades. During this time, the idea of employing nucleic acids as therapeutic agents has grown from little more than a concept to a clinical reality. Dr. Sullenger was one of the early pioneers in the field of nucleic acid therapeutics and continues to be recognized as a leader and innovator in this growing area of research.

Dr. Sullenger joined the faculty in the Departments of Surgery and Molecular Genetics and Microbiology at Duke in 1994 to explore the translational and clinical utility of RNA molecules. While at Duke he has developed an internationally recognized translational research program in RNA therapeutics. Dr. Sullenger is an inventor on numerous patents and is a scientific founder of three biotechnology companies that have raised well over $100 million to develop inventions that were created in his laboratory at Duke. For example, the Sullenger laboratory invented a novel and potentially safer strategy for anticoagulant therapy (Nature, 2002; Nature Biotechnology, 2004; Molecular Therapy, 2006; Nature Medicine, 2009). To translate this bench top discovery into a potentially useful therapeutic approach for treating cardiovascular disease patients, Dr. Sullenger founded a biotechnology company (Regado Biosciences Inc.) to raise the capital for the company to assemble the development expertise to move the novel therapeutic entity from his laboratory through IND enabling preclinical studies and into first in man clinical trials. The results from the first phase 1 study were published in 2006. Subsequently the therapeutic approach invented by Dr. Sullenger’s group has been evaluated in almost 1,000 patients in 90 medical centers around the world including a recent 650 patient phase 2b trial in the setting of Percutaneous Coronary Intervention (PCI). The results of this phase 2b study indicate that the drug-antidote invention made in the Sullenger lab may yield safer therapeutic agents for the millions of patients that require rapid anticoagulation each year and thereby improve patient outcomes for commonly performed medical procedures such as angioplasty and heart surgery. Recently the Sullenger laboratory demonstrated that RNA aptamers can be appended to siRNAs to selectively target them to cell surface receptors on prostate cancer cells (Nature Biotechnology, 2006). By delivering siRNAs specific for anti-apoptotic genes such as Plk1 the Sullenger group showed that this approach could be employed to selectively kill tumor cells in a murine xenograft model of prostate cancer. Currently, the Sullenger lab is continuing to explore the potential utility of such aptamer-siRNA chimeras and is focusing upon translating this research into a fist in man clinical study.
Dr. Sullenger was awarded the Joseph and Dorothy Beard Chair in Surgical Sciences in 2001 and he currently serves as Vice Chair for Research for the Department of Surgery at Duke. In 2004, Dr. Sullenger was awarded the Williams Faculty Research Prize and in 2006 and he was the recipient of the Duke Research Mentor of the Year in 2009. Dr. Sullenger was charged with the task of building the Duke Translational Research Institute in 2006 as was appointed its first Director that year, a position that he currently holds. He also currently serves a member of the Board of Directors of the Oligonucleotide Therapeutics Society. For his invention and work toward developing safer RNA-based therapeutic agents, Dr. Sullenger was the recipient of the Innovator/Researcher Health Care Hero Award in North Carolina in 2010.

Nucleic acid-binding polymers as anti-inflammatory agents.
Lee J, Sohn JW, Zhang Y, Leong KW, Pisetsky D, Sullenger BA.
Proc Natl Acad Sci U S A. 2011. 108:14055-60.

Development of universal antidotes to control aptamer activity.
Oney S, Lam RT, Bompiani KM, Blake CM, Quick G, Heidel JD, Liu JY, Mack BC, Davis ME, Leong KW, Sullenger BA.
Nat Med. 2009. 15:1224-8.

RNA aptamers as reversible antagonists of coagulation factor IXa.
Rusconi CP, Scardino E, Layzer J, Pitoc GA, Ortel TL, Monroe D, Sullenger BA.
Nature. 2002. 419:90-4.

Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras.
McNamara JO, Andrechek ER, Wang Y, Viles KD, Rempel RE, Gilboa E, Sullenger BA, Giangrande PH.
Nat Biotechnol. 2006. 24:1005-15.

Potent anticoagulant aptamer directed against factor IXa blocks macromolecular substrate interaction.
Sullenger B, Woodruff R, Monroe DM.
J Biol Chem. 2012. 287:12779-86.