Aptamer-targeted siRNA to Inhibit Nonsense Mediated Decay
Eli Gilboa and Fernando Pastor
Problem
Metastatic disease is often undetectable and/or inaccessible and is the primary cause of death among cancer patients. The approach described by this discovery accesses disseminated disease, is clinically feasible from the standpoint of cost, regulatory approval process, and complexity of treatment. Furthermore, the therapy should be broadly useful for all types of cancer and cancer patients.
Solution
An aptamers targeted small interference ribonucleic acid (siRNA) molecule that is capable of inhibiting nonsense mediated decay
Competitive Advantage
Novel method to treat metastatic disease.
Applications
Treatment of a variety of cancers
Patent Status
U.S. Provisional Patent Application. No. 61/219,502 entitled APTAMER-TARGETED SIRNA TO INHIBIT NONSENSE MEDIATED DECAY filed June 23, 2009
Licensing Opportunity
The University of Miami is seeking collaborative research and licensing options
About the Inventors
Dr. Eli Gilboa Ph.D., is the Director of the Dodson Interdisciplinary Immunotherapy Institute and Co-director of the Tumor Immunobiology & Immunotherapy Program at University of Miami Miller School of Medicine. Dr. Gilboa is one of the nations preeminent translational researchers bridging basic biomedical science and clinical research. Dr. Gilboa was one of the early pioneers of the fledgling field of gene therapy and played a key role at the dawn of this new era, developing the first generation of retroviral vectors used in the first human gene therapy trial by Dr. Rosenberg, Anderson and their colleagues. In a seminal study heralding the application of short RNA molecules (aptamers) for human therapy, he introduced the concept of RNA decoys to render cells resistant to HIV infection. Dr. Gilboa was also one of the early pioneers in the fields of cancer gene therapy demonstrating the potential of gene modified tumor cells as cancer vaccines. His current program is devoted to the development of multi-pronged strategies to engender protective immunity in the setting of cancer and infectious disease, developing potent vaccination strategies, manipulating immunomodulatory pathways, and targeting immune evasion mechanisms.
Dr. Gilboa received his Ph.D. in molecular biology at the Weizmann Institute, Rehovot, Israel, was an assistant professor in the Department of Molecular Biology at Princeton University, USA, from 1980-1986, and served as an associate member of the Memorial Sloan-Kettering Institute for Cancer Research Molecular Biology Program from 1986-1993. In 1993 Dr. Gilboa joined Duke University Medical Center as the Joseph and Dorothy Beard Professor of Experimental Surgery and Immunology and Director of the Center for Genetic and Cellular Therapies overseeing the development and clinical implementation of novel gene- and cell-based therapies. In September 2006 Dr. Gilboa joined the Sylvester Comprehensive Cancer Center and the Department of Microbiology & Immunology, Miller School of Medicine, University of Miami
Dr. Pastor has a PhD in immunology and is doing his postdoctoral training with Dr. Gilboa
Selected References
1. McNamara, J. O., D. Kolonias, F. Pastor, R.S. Mittler, L. Chen, P.H. Giangrande, B. Sullenger and E. Gilboa. Costimulation of CD8+ T cells and inhibition of tumor growth with multivalent 4-1BB binding aptamers. J. Clin. Invest., 118:376-386, 2008.
2. Gilboa, E. DC-based cancer vaccines. J Clin Invest 117:1195-1203,2007.
3. Nair, S., D. Boczkowski, M. Fassnacht, D. Pisetsky, and E. Gilboa.. Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity. Cancer Res 67:371-380, 2007
4. McNamara, J.O., 2nd, E.R. Andrechek, Y. Wang, K.D. Viles, R.E. Rempel, E. Gilboa, B.A. Sullenger, and P.H. Giangrande. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol 24:1005-1015, 2006.
5. Dannull, J., Z. Su, D. Rizzieri, B.K. Yang, D. Coleman, D. Yancey, A. Zhang, P. Dahm, N. Chao, E. Gilboa, and J. Vieweg. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest. 115:3623-3633, 2005
6. Gilboa, E. The promise of cancer vaccines. Nat Rev Cancer 4:401-411, 2004.
7. Gilboa, E., and J. Vieweg. Cancer immunotherapy with mRNA-transfected dendritic cells. Immunol Rev 199:251-263, 2004.
8. Santulli-Marotto, S., S.K. Nair, C. Rusconi, B. Sullenger, and E. Gilboa. Multivalent RNA aptamers that inhibit CTLA-4 and enhance tumor immunity. Cancer Res 63:7483-7489. 2003
9. Nair, S., D. Boczkowski, B. Moeller, M. Dewhirst, J. Vieweg, and E. Gilboa. Synergy between tumor immunotherapy and antiangiogenic therapy. Blood 102:964-971. 2003
10. Nair, S.K., A. Heiser, D. Boczkowski, A. Majumdar, M. Naoe, J.S. Lebkowski, J. Viweg, and E. Gilboa. Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells. Nature Medicine 6:1011-1017. 2000
