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.
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.
I. Introduction and Perspective.- 1 Antisense Methodology: An Assessment After 25 Years.- 2 Nucleic Acid Therapeutics: An Introduction.- II. Basic Methodology.- 3 Targeted Genome Modification Via Triple Helix Formation.- 4 Therapeutic Applications of Ribozymes.- 5 Use of Catalytic DNA in Target Validation and Therapeutics.- 6 Targeted Destruction of Small, Stable RNAs: Principles Applicable to Antisense Therapies.- 7 Mechanism of Action of Antisense RNA in Eukaryotic Cells.- III. Delivery.- 8 The Transport of Oligonucleotides Into Cells.- 9 Peptide-Mediated Delivery of Antisense Oligonucleotides and Related Material.- 10 Molecular Vectors for Gene Delivery to Cancer Cells.- IV. Targeting.- 11 Considerations on the Design of Antisense Oligonucleotides.- 12 Identification of Hybridization Accessible Sequence in Messenger RNA.- V. Clinical Targets.- 13 Nucleic Acids As Gene Targeting Therapeutics.- 14 LY900003 (Isis 3521) and G3139 (Genasense; Oblimersen): Phosphorothioate Antisense Oligonucleotides With Pleiotropic Mechanisms of Action.- 15 Antisense Protein Kinase A-RI? Restores Normal Signal Transduction Signatures to Inhibit Tumor Growth.
I. Introduction and Perspective.- 1 Antisense Methodology: An Assessment After 25 Years.- 2 Nucleic Acid Therapeutics: An Introduction.- II. Basic Methodology.- 3 Targeted Genome Modification Via Triple Helix Formation.- 4 Therapeutic Applications of Ribozymes.- 5 Use of Catalytic DNA in Target Validation and Therapeutics.- 6 Targeted Destruction of Small, Stable RNAs: Principles Applicable to Antisense Therapies.- 7 Mechanism of Action of Antisense RNA in Eukaryotic Cells.- III. Delivery.- 8 The Transport of Oligonucleotides Into Cells.- 9 Peptide-Mediated Delivery of Antisense Oligonucleotides and Related Material.- 10 Molecular Vectors for Gene Delivery to Cancer Cells.- IV. Targeting.- 11 Considerations on the Design of Antisense Oligonucleotides.- 12 Identification of Hybridization Accessible Sequence in Messenger RNA.- V. Clinical Targets.- 13 Nucleic Acids As Gene Targeting Therapeutics.- 14 LY900003 (Isis 3521) and G3139 (Genasense; Oblimersen): Phosphorothioate Antisense Oligonucleotides With Pleiotropic Mechanisms of Action.- 15 Antisense Protein Kinase A-RI? Restores Normal Signal Transduction Signatures to Inhibit Tumor Growth.
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