Part I. Introduction and Perspectiven n Antisense Methodology: An Assessment After 25 Yearsn Fritz Ecksteinn n Nucleic Acid Therapeutics: An Introductionn Alan M. Gewirtzn n Part II. Basic Methodologyn n Targeted Genome Modification Via Triple Helix Formationn Faye A. Rogers and Peter M. Glazern n Therapeutic Applications of Ribozymesn John J. Rossin n Use of Catalytic DNA in Target Validation and Therapeuticsn Lun-Quan Sunn n Targeted Destruction of Small, Stable RNAs: Principles Applicable to Antisense Therapiesn David A. Dunbar and Susan J. Basergan n Mechanism of Action of Antisense RNA in Eukaryotic Cellsn Zuo Zhang and Gordon G. Carmichaeln n Part III. Deliveryn n The Transport of Oligonucleotides Into Cellsn R. L. Julianon n Peptide-Mediated Delivery of Antisense Oligonucleotides and Related Materialn Eric Vivès, Jean Philippe Richard, and Bernard Lebleun n Molecular Vectors for Gene Delivery to Cancer Cellsn Guy Zuber, Jean-Serge Remy, Patrick Erbacher, Pascale Belguise, and Jean-Paul Behrn n Part IV. Targetingn n Considerations on the Design of Antisense Oligonucleotidesn Rosel Kretschmer-Kazemi Far, Jens M. Warnecke, and Georg Sczakieln n Identification of Hybridization Accessible Sequence in Messenger RNAn Lida K. Gifford, Ponzy Lu, and Alan M. Gewirtzn n Part V. Clinical Targetsn n Nucleic Acids As Gene Targeting Therapeuticsn Joanna B. Opalinska and Susan E. Shetzlinen n LY900003 (Isis 3521) and G3139 (Genasense; Oblimersen): Phosphorothioate Antisense Oligonucleotides With Pleiotropic Mechanisms of Actionn C. A. Stein, Nathalie Dias, Luba Benimetskaya, Jan S. Jepsen, Johnathan C. H. Lai, and Anthony J. Raffon n Antisense Protein Kinase A-RIa Restores Normal Signal Transduction Signatures to Inhibit Tumor Growthn Yoon S.Cho-Chungn n Index
A cutting-edge review of the important issues underlying the therapeutic use of nucleic acid-mediated gene silencing. Topics range from basic methodology and delivery to targeting and clinical targets. The authors thoroughly explain the latest developments in RNA biology, as well as the underpinnings of RNA interference, oligodeoxynucleotide delivery into cells, and strategies for targeting these molecules to accessible regions within the mRNA. They also provide some examples of how these new therapeutic compounds are being used clinically.