Edited by C. A. Stein and Arthur M. Krieg
The past fifteen years have seen major developments in the field of antisense oligonucleotide therapeutics. Antisense technology now yields large amounts of data in clinical trials and shows tremendous potential for therapeutic use in conditions ranging from cancers to infectious diseases. This volume features articles by scientists and academics at the leading edge of antisense research, presenting for the first time an overview of this dynamic, rapidly growing field.
Applied Antisense Oligonucleotide Technology offers a balanced discussion of theory and application, with an emphasis on the practical aspects associated with the use of antisense oligonucleotides to modify gene expression. This book describes critical areas of research and includes results of clinical studies and strategies for use of various agents. It also covers topics of general interest such as pharmacokinetics, toxicity considerations, and the non–antisense effects of oligonucleotides.
Complete with real–world examples and over one hundred illustrations, Applied Antisense Oligonucleotide Technology is presented in seven major parts:
∗ Oligonucleotide chemistry
∗ The mechanism of action and non–sequence specificity in oligodeoxynucleotide therapeutics
∗ Sequence–specific inhibition of gene expression and applied antisense oligonucleotide therapeutics
∗ Oligodeoxynucleotides as anti–HIV agents
∗ Therapeutic oligonucleotide data base, including pharmacokinetics, immune stimulation agents, and the use of oligonucleotides as antirestenotic agents
∗ Splicing and DNA triplex formation
∗ A review of the basic concepts in ribozyme technology
Applied Antisense Oligonucleotide Technology is an essential reference for researchers in biotechnology, genetics, and molecular biology. Easy to read and thoughtfully compiled by the co–editors of the journal Antisense Research and Development, this work is also accessible to researchers and academics in other areas, and anyone interested in pursuing this cutting–edge technology.
Oligonucleoside Methylphosphonates: Synthesis and Properties (P. Miller).
Oligo(Nucleoside Phosphorothioate)s (P. Guga, et al.).
Modified Oligodeoxynucleotides as Antisense Therapeutics (P. Seeberger & M. Caruthers).
Novel Chemistry (K. Altmann, et al.).
OLIGONUCLEOTIDE INTERNALIZATION, MECHANISM OF ACTION, AND NON–SEQUENCE SPECIFICITY.
Cellular Uptake and Biodistribution of Oligodeoxynucleotides (B. Hanss, et al.).
Use of Cationic Lipid Complexes for Antisense Oligonucleotide Delivery (C. Bennett).
Nonantisense Effects of Antisense Oligonucleotides (L. Neckers & K. Iyer).
Ribonuclease H–Mediated Antisense Effects of Oligonucleotides and Controls for Antisense Experiments (D. Tidd).
SEQUENCE–SPECIFIC INHIBITION OF GENE EXPRESSION.
The Development of C–5 Propyne Oligonucleotides as Inhibitors of Gene Function (W. Flanagan & R. Wagner).
The Use of Antisense Oligonucleotides to Inhibit Expression of Isozymes of Protein Kinase C (N. Dean, et al.).
BCR–ABL as a Target for Antisense Intervention (S. O′Brien & T. Smetsers).
The NF–kB Transcription Factor (R. Narayanan).
Disruption of the Map Kinase Signaling Pathway Using Antisense Oligonucleotide Inhibitors Targeted to RAS and RAF Kinase (B. Monia).
Protein Kinase A–Directed Antisense Blockade of Cancer Growth: Single Gene–Based Therapeutic Approach (Y. Cho–Chung).
Use of Antisense Oligonucleotides in the Central Nervous System: Why Such Success?
APPLIED ANTISENSE OLIGONUCLEOTIDE THERAPEUTICS.
Perturbing Hematopoietic Cell Gene Expression with Oligodeoxynucleotides: Research and Clinical Applications (A. Gewirtz & M. Ratajczak).
BCL2 (B. Jansen & B. Brown).
Biological Activity of Guanosine Quartet–Forming Oligonucleotides (R. Rando & M. Hogan).
OLIGONUCLEOTIDES AS ANTI–HIV AGENTS.
Perspectives on Antisense Technology Against HIV (J. Gee, et al.).
In Vivo Pharmacokinetics of Oligonucleotides (S. Agrawal).
Early Clinical Trails with Gem 91, A Systemic Oligodeoxynucleotide (R. Martin).
THERAPEUTIC OLIGONUCLEOTIDE DATA BASE: PHARMACOKINETICS, IMMUNE STIMULATION, AND USE AS ANTIRESTENOTIC AGENTS.
Antisense Therapy to Inhibit Angioplasty Restenosis (L. Rabbani & W. Wang).
Pharmacokinetics of Oligonucleotides: A Review of Current Knowledge and Issues for the Future (T. Wallace & P. Cossum).
Leukocyte Stimulation by Oligodeoxynucleotides (A. Krieg).
SELECTED OLIGODEOXYNUCLEOTIDE DEVELOPMENTAL TOPICS: SPLICING AND TRIPLEXES.
Modification of Alternative Splicing of Pre–mRNA by Antisense Oligonucleotides (R. Kole).
Gene–Targeted Triple–Helix–Forming Oligonucleotides (F. Svinarchuk & C. Malvy).
Triplex–Forming Oligonucleotides for Genetic Manipulation: An Alternative View (A. Faruqi & P. Glazer).
A REVIEW OF RIBOZYME TECHNOLOGY.
Therapeutic Ribozymes: Principles, Applications, and Problems (J. Rossi).