The potential for the development of therapeutic oligonucleotides into clinical medicines and their use as basic research tools are explored in this volume, which is the proceedings of the 7th NIH Symposium on Therapeutic Oligonucleotides. The focus is on antisense, RNAi, triple–helix, gene repair, DNA chips, and CpG immune modulatory oligonucleotides.
Specific chapters address designing better siRNAs, splice switching oligonucleotides, selective delivery of oligonucleotides, and medicinal drugs by receptor–mediated endocytosis, development of a function overriding siRNA silencing in mammalian cells, transcription factor decoys, and modified oligonucleotide hybridization and genetic insertion.
Introduction: Y S Cho–Chung, Alan M. Gewirtz, and Cy A. Stein.
Part I: Kill the Messenger: Gene Silencing by Nucleic Acid Molecules.
1. Knock–down of the Cytoprotective Gene, Clusterin, to Enhance Hormone and Chemosensitivity in Prostate and Other Cancers: Martin Gleave and Kim N. Chi.
2. Recognition of Chromosomal DNA in Human Cells by Peptide Nucleic Acids and Small Duplex RNAs: David R. Corey.
Part II: Antisense and siRNA: Chemistry, Sequence Specificity, and Target Validation.
3. Design and Development of Thermolytic DNA Oligonucleotide Prodrugs: Andrzej Grajkowski, Joao Pedras–Vasconcelos, Cristina Ausín, Daniela Verthelyi, and Serge L. Beaucage.
4. Rationally Targeted, Conformationally Constrained, Oxetane–Modified Oligonucleotides Demonstrate Efficient Gene–Silencing Activity in a Cellular System: J B Opalinska and A M Gewirtz.
Part III: Delivery Cellular and Phenotype Effect of Silencing Agents:.
5. In Vivo Potentialities Andrei Maksimenko, Valerie Polard, Marie Villemeur, Hind Elhamess, Patrick Couvreur, Jean–Remi Bertrand, Malam Aboubakar, Marina Gottikh, and Claude Malvy of EWS–Fli–1 Targeted Antisense Oligonucleotides–Nanospheres Complexes:.
6. Endo–Porter: A Novel Reagent for Safe, Effective Delivery of Substances into Cells: James E. Summerton.
7. Tumor Reversion: Protein Kinase A Isozyme Switching: Yoon S. Cho–Chung and Maria V. Nesterova.
Part IV: Immune Modulation of and Resistance to Silencing Agents.
8. Therapeutic Potential of Oligonucleotides Expressing Immunosuppressive TTAGGG Motifs: Dennis M. Klinman, Ihsan Gursel, Sven Klaschik, Li Dong, Debbie Currie, and Hidekazu Shirota.
9. Breaking Tolerance to Tumors with Dendritic Cell–Based Immunotherapy: Ines Mende and Edgar G. Engleman.
10. Development of Resistance to RNAi in Mammalian Cells: Zhi–Ming Zheng, Shuang Tang, and Mingfang Tao.
Part V: Transcription Silencing by Nucleic Acid Molecules.
11. The Development of Bioactive Triple Helix–Forming Oligonucleotides: Michael M. Seidman, Nitin Puri, Alokes Majumdar, Bernard Cuenoud, Paul S. Miller, and Rowshon Alam.
12. Transcription Factor Decoys: A New Model for Disease Intervention: Michael J. Mann.
13. DNA Damage Produced by 125I–Triplex–Forming Oligonucleotides as a Measure of Their Succesful Delivery into Cell Nuclei: Irina V. Panyutin, Olga A. Sedelnikova, William M. Bonner, Igor G. Panyutin, and Ronald D. Neumann.
14. Targeted Genome Modification via Triple Helix Formation: Jennifer M. Kalish and Peter M. Glazer.
Part VI: Functional Genomics Antisense/RNAi.
15. "Promoter Array" Studies Identify Cohorts of Genes Directly Regulated by Methylation, Copy Number Change, or Transcription Factor Binding in Human Cancer Cells: Yipeng Wang, Jun Hayakawa, Fred Long, Qiuju Yu, Ann H. Cho, Gaelle Rondeau, John Welsh, Shalu Mittal, Ian De Belle, Eileen Adamson, Michael Mcclelland, and Dan Mercola.
16. Application of Expression Genomics for Predicting Treatment Response in Cancer: Khew–Voon Chin, Leah Alabanza, Kazuyuki Fujii, Kazuya Kudoh, Tsunekazu Kita, Yoshihiro Kikuchi, Zachariah E. Selvanayagam, Yick Fu Wong, Yong Lin, and Wei Chung Shih.
17. Stability Regulation of mRNA and the Control of Gene Expression: Chris Cheadle, Jinshui Fan, Yoon S. Cho–Chung, Thomas Werner, Jill Ray, Lana Do, Myriam Gorospe, and Kevin G. Becker.
Part VII: Chemosensitivity Enhancement by Antisense and RNAi.
18. Novel MDM2 p53–Independent Functions Identified through RNA Silencing Technologies: Zhuo Zhang, Hui Wang, Mao Li, Elizabeth Rayburn, Sudhir Agrawal, and Ruiwen Zhang.
19. Application of XIAP Antisense to Cancer and Other Proliferative Disorders: Development of AEG35156/ GEM®640: Eric C. Lacasse, Ekambar R. Kandimalla, Peter Winocour, Tim Sullivan, Sudhir Agrawal, John W. Gillard, and Jon Durkin.
Part VIII: Nucleic Acid Therapeutics for Human Diseases.
20. Induction of Apoptosis by G3139 in Melanoma Cells: Luba Benimetskaya, Johnathan C. Lai, Anastasia Khvorova, Sijian Wu, Paul Miller, and C A Stein.
21. Zebularine: A Unique Molecule for an Epigenetically Based Strategy in Cancer Chemotherapy: Victor E. Marquez, James A. Kelley, Riad Agbaria, Tisipi Ben–Kasus, Jonathan C. Cheng, Christine B. Yoo, and Peter A. Jones.