Bruce Alan Sullenger

Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery

The main focus of my translational research laboratory is to develop RNA based therapeutic agents for the potential treatment of a range of diseases. To this end, we have and will continue to take advantage of the fact that RNA is not just a passive carrier of genetic instructions inside of cells during the conversion of information from DNA to RNA to protein. Rather, RNA is an extremely versatile biological macromolecule. Certian RNAs can bind to specific protiens with high affinities, while others can for catalytic centers and perform enzymatic reactions. These facets of RNA coupled with the ease with which RNA can be manipulated in vitro make it a very powerful and unique therapeutic agent whose potential is largely untapped. Durring our endeavors, we plan to work closely with the members of the Molecular Therapeutics program as well as other faculty at the Duke University Medical Center to expedite the development and testing of these therapeutics.

The specific aims of my laboratory are:

1. To isolate and characterize RNA and DNA aptamers which block therapeutically relavent proteins such as those involved in cardiovascular diseases and immune modulation.

2. To develop RNA-based tumor targeting strategies for delivering siRNAs and miRNAs to tumor cells.

3. To reprogram cells using mRNA delivery.

4. To explore novel methods to control inflammation.

Appointments and Affiliations

  • Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery
  • Professor in Surgery
  • Director of the Duke Center for Translational Research
  • Professor of Pharmacology and Cancer Biology
  • Professor of Neurosurgery
  • Professor of Cell Biology
  • Member of the Duke Cancer Institute

Contact Information

  • Office Location: 120 Serrano Way, Chapel Hill, NC 27517
  • Office Phone: (919) 451-8921
  • Email Address: bruce.sullenger@duke.edu

Education

  • Ph.D. Cornell University, 1990

In the News

Representative Publications

  • Buddai, Sai K., Juliana M. Layzer, Genmin Lu, Christopher P. Rusconi, Bruce A. Sullenger, Dougald M. Monroe, and Sriram Krishnaswamy. “An anticoagulant RNA aptamer that inhibits proteinase-cofactor interactions within prothrombinase.” J Biol Chem 285, no. 8 (February 19, 2010): 5212–23. https://doi.org/10.1074/jbc.M109.049833.
  • Wang, Jialiang, Timothy P. Wakeman, Justin D. Lathia, Anita B. Hjelmeland, Xiao-Fan Wang, Rebekah R. White, Jeremy N. Rich, and Bruce A. Sullenger. “Notch promotes radioresistance of glioma stem cells.” Stem Cells 28, no. 1 (January 2010): 17–28. https://doi.org/10.1002/stem.261.
  • Mi, Jing, Yingmiao Liu, Zahid N. Rabbani, Zhongguang Yang, Johannes H. Urban, Bruce A. Sullenger, and Bryan M. Clary. “In vivo selection of tumor-targeting RNA motifs.” Nat Chem Biol 6, no. 1 (January 2010): 22–24. https://doi.org/10.1038/nchembio.277.
  • Oney, Sabah, Ruby T. S. Lam, Kristin M. Bompiani, Charlene M. Blake, George Quick, Jeremy D. Heidel, Joanna Yi-Ching Liu, et al. “Development of universal antidotes to control aptamer activity.” Nat Med 15, no. 10 (October 2009): 1224–28. https://doi.org/10.1038/nm.1990.
  • Blake, Charlene M., Bruce A. Sullenger, Daniel A. Lawrence, and Yolanda M. Fortenberry. “Antimetastatic potential of PAI-1-specific RNA aptamers.” Oligonucleotides 19, no. 2 (June 2009): 117–28. https://doi.org/10.1089/oli.2008.0177.
  • Long, Stephen B., Meredith B. Long, Rebekah R. White, and Bruce A. Sullenger. “Crystal structure of an RNA aptamer bound to thrombin.” Rna 14, no. 12 (December 2008): 2504–12. https://doi.org/10.1261/rna.1239308.
  • Dollins, Claudia M., Smita Nair, David Boczkowski, Jaewoo Lee, Juliana M. Layzer, Eli Gilboa, and Bruce A. Sullenger. “Assembling OX40 aptamers on a molecular scaffold to create a receptor-activating aptamer.” Chem Biol 15, no. 7 (July 21, 2008): 675–82. https://doi.org/10.1016/j.chembiol.2008.05.016.
  • Giangrande, Paloma H., JianXin Zhang, Alice Tanner, Andrea D. Eckhart, Rachel E. Rempel, Eran R. Andrechek, Juliana M. Layzer, et al. “Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia.” Proc Natl Acad Sci U S A 104, no. 32 (August 7, 2007): 12988–93. https://doi.org/10.1073/pnas.0704754104.
  • Kierlin-Duncan, Monique N., and Bruce A. Sullenger. “Using 5'-PTMs to repair mutant beta-globin transcripts.” Rna 13, no. 8 (August 2007): 1317–27. https://doi.org/10.1261/rna.525607.
  • Nimjee, Shahid M., J. R. Keys, G. A. Pitoc, G. Quick, C. P. Rusconi, and Bruce A. Sullenger. “A novel antidote-controlled anticoagulant reduces thrombin generation and inflammation and improves cardiac function in cardiopulmonary bypass surgery.” Mol Ther 14, no. 3 (September 2006): 408–15. https://doi.org/10.1016/j.ymthe.2006.04.006.
  • McNamara, James O., Eran R. Andrechek, Yong Wang, Kristi D. Viles, Rachel E. Rempel, Eli Gilboa, Bruce A. Sullenger, and Paloma H. Giangrande. “Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras.” Nat Biotechnol 24, no. 8 (August 2006): 1005–15. https://doi.org/10.1038/nbt1223.
  • Jones, John Patrick, Monique N. Kierlin, Robert G. Coon, Jiri Perutka, Alan M. Lambowitz, and Bruce A. Sullenger. “Retargeting mobile group II introns to repair mutant genes.” Mol Ther 11, no. 5 (May 2005): 687–94. https://doi.org/10.1016/j.ymthe.2005.01.014.
  • Nimjee, Shahid M., Christopher P. Rusconi, and Bruce A. Sullenger. “Aptamers: an emerging class of therapeutics.” Annu Rev Med 56 (2005): 555–83. https://doi.org/10.1146/annurev.med.56.062904.144915.
  • Rusconi, Christopher P., Joseph D. Roberts, George A. Pitoc, Shahid M. Nimjee, Rebekah R. White, George Quick, Elizabeth Scardino, William P. Fay, and Bruce A. Sullenger. “Antidote-mediated control of an anticoagulant aptamer in vivo.” Nat Biotechnol 22, no. 11 (November 2004): 1423–28. https://doi.org/10.1038/nbt1023.
  • Layzer, Juliana M., Anton P. McCaffrey, Alice K. Tanner, Zan Huang, Mark A. Kay, and Bruce A. Sullenger. “In vivo activity of nuclease-resistant siRNAs.” Rna 10, no. 5 (May 2004): 766–71. https://doi.org/10.1261/rna.5239604.
  • Byun, Jonghoe, Ning Lan, Meredith Long, and Bruce A. Sullenger. “Efficient and specific repair of sickle beta-globin RNA by trans-splicing ribozymes.” Rna 9, no. 10 (October 2003): 1254–63. https://doi.org/10.1261/rna.5450203.
  • White, Rebekah R., Siqing Shan, Christopher P. Rusconi, Geetha Shetty, Mark W. Dewhirst, Christopher D. Kontos, and Bruce A. Sullenger. “Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2.” Proc Natl Acad Sci U S A 100, no. 9 (April 29, 2003): 5028–33. https://doi.org/10.1073/pnas.0831159100.
  • Rogers, Christopher S., Carlos G. Vanoye, Bruce A. Sullenger, and Alfred L. George. “Functional repair of a mutant chloride channel using a trans-splicing ribozyme.” J Clin Invest 110, no. 12 (December 2002): 1783–89. https://doi.org/10.1172/JCI16481.
  • Rusconi, Christopher P., Elizabeth Scardino, Juliana Layzer, George A. Pitoc, Thomas L. Ortel, Dougald Monroe, and Bruce A. Sullenger. “RNA aptamers as reversible antagonists of coagulation factor IXa.” Nature 419, no. 6902 (September 5, 2002): 90–94. https://doi.org/10.1038/nature00963.
  • Sullenger, Bruce A., and Eli Gilboa. “Emerging clinical applications of RNA.” Nature 418, no. 6894 (July 11, 2002): 252–58. https://doi.org/10.1038/418252a.
  • Martell, Robert E., Joseph R. Nevins, and Bruce A. Sullenger. “Optimizing aptamer activity for gene therapy applications using expression cassette SELEX.” Mol Ther 6, no. 1 (July 2002): 30–34. https://doi.org/10.1006/mthe.2002.0624.
  • Watanabe, T., and B. A. Sullenger. “RNA repair: a novel approach to gene therapy.” Adv Drug Deliv Rev 44, no. 2–3 (November 15, 2000): 109–18. https://doi.org/10.1016/s0169-409x(00)00089-2.
  • Rusconi, C. P., A. Yeh, H. K. Lyerly, J. H. Lawson, and B. A. Sullenger. “Blocking the initiation of coagulation by RNA aptamers to factor VIIa.” Thromb Haemost 84, no. 5 (November 2000): 841–48.
  • Sullenger, B. A. “Series introduction: emerging clinical applications of nucleic acids.” J Clin Invest 106, no. 8 (October 2000): 921–22. https://doi.org/10.1172/JCI11343.
  • White, R. R., B. A. Sullenger, and C. P. Rusconi. “Developing aptamers into therapeutics.” J Clin Invest 106, no. 8 (October 2000): 929–34. https://doi.org/10.1172/JCI11325.
  • Lan, N., B. L. Rooney, S. W. Lee, R. P. Howrey, C. A. Smith, and B. A. Sullenger. “Enhancing RNA repair efficiency by combining trans-splicing ribozymes that recognize different accessible sites on a target RNA.” Mol Ther 2, no. 3 (September 2000): 245–55. https://doi.org/10.1006/mthe.2000.0125.
  • Watanabe, T., and B. A. Sullenger. “Induction of wild-type p53 activity in human cancer cells by ribozymes that repair mutant p53 transcripts.” Proc Natl Acad Sci U S A 97, no. 15 (July 18, 2000): 8490–94. https://doi.org/10.1073/pnas.150104097.
  • Long, M. B., and B. A. Sullenger. “Evaluating group I intron catalytic efficiency in mammalian cells.” Mol Cell Biol 19, no. 10 (October 1999): 6479–87. https://doi.org/10.1128/MCB.19.10.6479.
  • Sullenger, B. A. “RNA repair as a novel approach to genetic therapy.” Gene Ther 6, no. 4 (April 1999): 461–62. https://doi.org/10.1038/sj.gt.3300903.
  • Zarrinkar, P. P., and B. A. Sullenger. “Optimizing the substrate specificity of a group I intron ribozyme.” Biochemistry 38, no. 11 (March 16, 1999): 3426–32. https://doi.org/10.1021/bi982688m.
  • Zarrinkar, P. P., and B. A. Sullenger. “Probing the interplay between the two steps of group I intron splicing: competition of exogenous guanosine with omega G.” Biochemistry 37, no. 51 (December 22, 1998): 18056–63. https://doi.org/10.1021/bi982193x.
  • Lan, N., R. P. Howrey, S. W. Lee, C. A. Smith, and B. A. Sullenger. “Ribozyme-mediated repair of sickle beta-globin mRNAs in erythrocyte precursors.” Science 280, no. 5369 (June 5, 1998): 1593–96. https://doi.org/10.1126/science.280.5369.1593.
  • Jones, J. T., and B. A. Sullenger. “Evaluating and enhancing ribozyme reaction efficiency in mammalian cells.” Nat Biotechnol 15, no. 9 (September 1997): 902–5. https://doi.org/10.1038/nbt0997-902.
  • Lee, S. W., and B. A. Sullenger. “Isolation of a nuclease-resistant decoy RNA that can protect human acetylcholine receptors from myasthenic antibodies.” Nat Biotechnol 15, no. 1 (January 1997): 41–45. https://doi.org/10.1038/nbt0197-41.
  • Jones, J. T., S. W. Lee, and B. A. Sullenger. “Trans-splicing reactions by ribozymes.” Methods Mol Biol 74 (1997): 341–48. https://doi.org/10.1385/0-89603-389-9:341.
  • Ishizaki, J., J. R. Nevins, and B. A. Sullenger. “Inhibition of cell proliferation by an RNA ligand that selectively blocks E2F function.” Nat Med 2, no. 12 (December 1996): 1386–89. https://doi.org/10.1038/nm1296-1386.
  • Sullenger, B. A. “Ribozyme-mediated repair of RNAs encoding mutant tumor suppressors.” Cytokines Mol Ther 2, no. 3 (September 1996): 201–5.
  • Lee, S. W., and B. A. Sullenger. “Isolation of a nuclease-resistant decoy RNA that selectively blocks autoantibody binding to insulin receptors on human lymphocytes.” J Exp Med 184, no. 2 (August 1, 1996): 315–24. https://doi.org/10.1084/jem.184.2.315.
  • Jones, J. T., S. W. Lee, and B. A. Sullenger. “Tagging ribozyme reaction sites to follow trans-splicing in mammalian cells.” Nat Med 2, no. 6 (June 1996): 643–48. https://doi.org/10.1038/nm0696-643.
  • Sullenger, B. A. “Revising messages traveling along the cellular information superhighway.” Chem Biol 2, no. 5 (May 1995): 249–53. https://doi.org/10.1016/1074-5521(95)90043-8.
  • Doudna, J. A., T. R. Cech, and B. A. Sullenger. “Selection of an RNA molecule that mimics a major autoantigenic epitope of human insulin receptor.” Proc Natl Acad Sci U S A 92, no. 6 (March 14, 1995): 2355–59. https://doi.org/10.1073/pnas.92.6.2355.
  • Sullenger, B. A. “Colocalizing ribozymes with substrate RNAs to increase their efficacy as gene inhibitors.” Appl Biochem Biotechnol 54, no. 1–3 (1995): 57–61. https://doi.org/10.1007/BF02787911.
  • Smith, C., and B. A. Sullenger. “AIDS and HIV infection.” Mol Cell Biol Hum Dis Ser 5 (1995): 195–236. https://doi.org/10.1007/978-94-011-0547-7_11.
  • Campbell, T. B., and B. A. Sullenger. “Alternative approaches for the application of ribozymes as gene therapies for retroviral infections.” Adv Pharmacol 33 (1995): 143–78. https://doi.org/10.1016/s1054-3589(08)60668-7.
  • Sullenger, B. A., and T. R. Cech. “Ribozyme-mediated repair of defective mRNA by targeted, trans-splicing.” Nature 371, no. 6498 (October 1994): 619–22. https://doi.org/10.1038/371619a0.
  • Sullenger, B. A., and T. R. Cech. “Tethering ribozymes to a retroviral packaging signal for destruction of viral RNA.” Science 262, no. 5139 (December 3, 1993): 1566–69. https://doi.org/10.1126/science.8248806.
  • Lee, T. C., B. A. Sullenger, H. F. Gallardo, G. E. Ungers, and E. Gilboa. “Overexpression of RRE-derived sequences inhibits HIV-1 replication in CEM cells.” New Biol 4, no. 1 (January 1992): 66–74.
  • Sullenger, B. A., H. F. Gallardo, G. E. Ungers, and E. Gilboa. “Analysis of trans-acting response decoy RNA-mediated inhibition of human immunodeficiency virus type 1 transactivation.” J Virol 65, no. 12 (December 1991): 6811–16. https://doi.org/10.1128/JVI.65.12.6811-6816.1991.
  • Sullenger, B. A., T. C. Lee, C. A. Smith, G. E. Ungers, and E. Gilboa. “Expression of chimeric tRNA-driven antisense transcripts renders NIH 3T3 cells highly resistant to Moloney murine leukemia virus replication.” Mol Cell Biol 10, no. 12 (December 1990): 6512–23. https://doi.org/10.1128/mcb.10.12.6512-6523.1990.
  • Sullenger, B. A., H. F. Gallardo, G. E. Ungers, and E. Gilboa. “Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication.” Cell 63, no. 3 (November 1990): 601–8. https://doi.org/10.1016/0092-8674(90)90455-n.
  • Hantzopoulos, P. A., B. A. Sullenger, G. Ungers, and E. Gilboa. “Improved gene expression upon transfer of the adenosine deaminase minigene outside the transcriptional unit of a retroviral vector.” Proc Natl Acad Sci U S A 86, no. 10 (May 1989): 3519–23. https://doi.org/10.1073/pnas.86.10.3519.