Stanley T. Crooke

Sudhir Agrawal

Antisense Research and Application

Extensively revised and updated, Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition reflects the logarithmic progress made in the past four years of oligonucleotide-based therapies, and, in particular, antisense therapeutics and research. Interpreting lessons learned from the clinical trials of first generation drugs, the book evaluates the technology as a whole and offers new directions and avenues of research and development. Divided into five parts, the book begins with a thorough introduction to the mechanism of antisense drug action including the RNase H mechanism, small RNA silencing pathways, and the potential therapeutics of splice switching oligonucleotides. Leading researchers demonstrate the basics of oligonucleotide therapeutics in part two by delineating medicinal chemistry, pharmacokinetics, and delivery routes such as liposomal formulations for nucleic acid delivery. Part three details hybridization based drugs and considers the dramatic advances represented by 2’ methoxyethyl chimeric antisense inhibitors and duplex RNA drugs. Other chemical classes of drugs and mechanisms of action are described in part four with further discussions on improving the second generation antisense drugs. The final part delves deeply into therapeutic applications. Contributing authors examine the potential of antisense drugs for the alleviation of cardiovascular diseases, metabolic diseases, inflammatory diseases, cancer, neurological disorders, and immune modulation. Presenting a highly detailed, lucid discussion of the remarkable advances in the field, Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition provides the platform for researchers to continue to aggressively pursue the great opportunity represented by this exciting technology.

Principles, Strategies, and Applications, Second Edition

Antisense Drug Technology

George Poste

Dopamine, in addition to its importance as a precursor of norepinephrine, is now known to be an important neurotransmitter in regulating functional activities in a number of major organ systems, including the central ner vous system. the cardiovascular system, the kidney, and the gut. Recent advances in our understanding of the functional role of dopamine, its mechanism of action and the pharmacology of dopaminergic agents have occurred on a broad front. The last few years have witnessed significant progress in the identification and classification of central and peripheral dopamine receptors and the factors that affect their responsiveness to inhibitory and stimulatory ligands. These advances have been paralleled by new insights into the contribution of alterations in dopaminergic reg ulation in causing disease and the utility of dopamine agonists and an tagonists as therapeutic modalities. This volume, the first in a series of publications arising from the annual Smith Kline and French Research Symposium on New Horizons in Therapeutics, provides a comprehensive survey of current research on peripheral dopamine receptors and the physiologic and therapeutic con sequences of stimulating pre-and postsynaptic dopamine receptors. Research in dopamine pharmacology mirrors the remarkable ad vances that are occurring in the field of pharmacology at large as a con sequence of the involvement of an ever-larger number of scientific dis ciplines in the study of drug action.

Dopamine Receptor Agonists

This state-of-the-art reference provides comprehensive coverage of the development of antisense oligonucleotides to inhibit cancer cells as well as those involved in infectious, inflammatory, and immune-mediated diseases-highlighting new tools and technologies in medicinal chemistry, RNA biochemistry, and molecular and cellular biology to produce new therapeutic compounds. Presents previously unpublished data on the use of antisense technology to dissect pharmacological processes and confirm the roles of various genes! Showcasing the benefits of antisense drug use, including reduced toxicity and earlier disease detection, Antisense Drug Technology discusses novel formulations of antisense drugs practical methods to design effective isotype selective inhibitors molecular mechanisms of antisense drugs mRNA as a current biological template modern postreceptor binding mechanisms and more! With contributions by over 60 seasoned experts in the field and containing more than 3000 helpful references, tables, drawings, and photographs, Antisense Drug Technology is an illuminating source for organic, medicinal, and pharmaceutical chemists; biochemists; geneticists; hematologists; oncologists; molecular and cell biologists; virologists; immunologists; and medical school and graduate students in these disciplines.

Principles: Strategies, and Applications

It is less than 80 years since John Newport Langley first proposed the role of "receptive substances" as the site of drug action from his obser vations on the effects of nicotine and curare at the myoneural junction. The many advances in our understanding of receptor biology that have occurred during the intervening period mirror the extraordinary growth of knowledge in the biological sciences and in cell and molecular biology in particular. Receptor biology, in common with many other topics in contemporary biology, is on the threshold of a transition from being a descriptive, phenomenological discipline to one in which underlying mechanisms and regulatory principles can be defined with increasing pre cision. This change, together with the evolution of powerful analytical techniques and timely convergence of ideas from a number of previously separate fields of inquiry, is generating an increasingly unified theoretical and experimental framework for the study of receptor function. These themes, and the mood of anticipation that a real understanding of receptor function in health and disease is emerging, are reflected in in this volume, which summarizes the proceedings of the Sec the papers ond Smith Kline & French Research Symposium on New Horizons in Therapeutics held in Philadelphia in 1984.

Mechanisms of Receptor Regulation

Antisense technology may result in dramatic changes in the therapy of many diseases and may provide tools to dissect pharmacological processes and to confirm the roles of various genes. In this volume, progress in the understanding of antisense technology and its use in creating new drugs is discussed. Potential caveats, pitfalls and limitations of the technology are also presented. In the next few years the pace at which new molecular targets will be identified will increase exponentially as the sequencing of the human genome and of other genomes proceeds.

Bernard Lebleu

Antisense Research and Applications is a comprehensive review of oligonucleotide research covering molecular biological advances in this field, the current status of antisense drug research, and strategies for future research and therapeutic applications. In bringing together the latest research from an array of authoritative scientists, Antisense Research and Applications provides an integrated conceptual basis for considering oligonucleotide therapeutics. Topics covered in the 32 chapters of this book include nucleic acid structure and function, antisense RNA, medicinal chemistry of oligonucleotides, analogs, pharmacokinetics and toxicology, and activities of current antisense drugs. This volume addresses advances in a broad range of disciplines and is an excellent resource for basic researchers and applied investigators in pharmaceutical laboratories and in such fields as biochemistry and molecular biology.

Stanley T. Crooke

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