Perspectives in Antisense Science - Böcker

When first introduced, antisense oligonucleotides were hailed as the long awaited magic bullet that would provide an unprecedented level of specificity in controlling gene expression. Following this initial enthusiasm, antisense oligonucleotides have been maligned as nonspecific, toxic, and essentially useless. However, application of antisense oligonucleotide technology in the nervous system stands apart from the use of this technique in peripheral systems, largely because of its enormous success. The source of this success remains a matter of some controversy. This text addresses the origins of that controversy and determines whether the nervous system is a privileged site for antisense oligonucleotide action an d not subject to the same vagaries and pitfalls as non-neuronal systems. It contains chapters by experts in the field that focus on the use of this technique in a variety of behavioural systems, as well as rapid and nonspecific effects and the uptake and metabolism of antisense oligonucleotides by the nervous system.

Considers the different aspects of the design and improvement of triple helix forming oligonucleotides, these molecules and their structural analysis, as well as their applications, with special emphasis on the attempts to obtain biological effects of these potentially important tools. What emerges is that the research is encouraging, and that these molecules are already useful in some biotechnology applications. Sequence-specific DNA binding ligands, amongst which triple helix forming oligonucleotides are the most efficient as yet, represent promising tools in a number of fields. One of their most promising applications is as antiviral tools: they can specifically target a viral gene, even if it is integrated into the host genome, and be used to specifically inactivate the viral gene or even destroy the cells harboring this gene. However, from science fiction to science there remains a gap; and we are at the moment on the threshold of this fascinating field.

Restenosis, the proliferation of smooth muscle cells (SMC) that line blood vessels, often follows angioplasty. Despite advances in cardiology, restenosis continues to affect up to 40% of the over 500,000 patients who undergo angioplasty each year. Applications of Antisense Therapies to Restenosis is the first volume to address the potential of using antisense therapies to inhibit the restenosis that occurs after percutaneous transluminal angioplasty and coronary stenting. The work critically examines the application of various antisense therapies for inhibiting restenosis.

In the late-90s, antisense methodology has moved from in vitro studies to in vivo studies and first human trials. While the basic concept of antisense technology is simple, the methodological problems associated with its use are numerous and complex. Antisense-based methods have proven to be a field of research where careful attention to experimental protocols and appropriate controls is necessary. This book emphasizes the application of antisense oligonucleotides, and is a guide for the identification of antisense and non-antisense effects in different experimental settings. The work is organized into three sections, antisense application in vitro, antisense application in vivo (animal models) and finally, clinical antisense studies. Where at all possible, the methods are described in sufficient detail to allow reproduction of a given experiment. It should be of interest to researchers in immunology, cancer research, pharmacology and internal medicine; and physicians conducting clinical studies in these fields.

When first introduced, antisense oligonucleotides were hailed as the long awaited magic bullet that would provide an unprecedented level of specificity in controlling gene expression. Following this initial enthusiasm, antisense oligonucleotides have been maligned as nonspecific, toxic, and essentially useless. However, application of antisense oligonucleotide technology in the nervous system stands apart from the use of this technique in peripheral systems, largely because of its enormous success. The source of this success remains a matter of some controversy.Modulating Gene Expression by Antisense Oligonucleotides to Understand Neural Functioning addresses the origins of that controversy and determines whether the nervous system is a privileged site for antisense oligonucleotide action and not subject to the same vagaries and pitfalls as non-neuronal systems. Modulating Gene Expression by Antisense Oligonucleotides to Understand Neural Functioning contains chapters by experts in the field that focus on the use of this technique in a variety of behavioral systems, as well as rapid and nonspecific effects and the uptake and metabolism of antisense oligonucleotides by the nervous system. Modulating Gene Expression by Antisense Oligonucleotides to Understand Neural Functioning features: experts in the field reporting on the use of antisense oligonucleotide technology in a variety of behavioral systems, including pain control, circadian rhythms, ingestion and control of water balance, and reproductive behaviors; the novel use of plasmids to express antisense RNA in the nervous system; the biodistribution and metabolism of antisense oligonucleotides in the nervous system; rapid and unusual effects; and non-specific effects.

In the past few years, antisense methodology has moved from in vitro studies to in vivo studies and first human trials. The work is organized into three sections: antisense application in vitro, antisense application in vivo (animal models) and finally, clinical antisense studies.

Sequence-specific DNA binding ligands, amongst which triple helix forming oligonucleotides are the most efficient as yet, represent promising tools in a number of fields. One of their most promising applications is as antiviral tools: they can specifically target a viral gene, even if it is integrated into the host genome, and be used to specifically inactivate the viral gene or even destroy the cells harboring this gene. However, from science fiction to science there remains a gap; and we are at the moment on the threshold of this fascinating field. Triple Helix Forming Oligonucleotides considers the different aspects of the design and improvement, current or future, of these molecules and their structural analysis, as well as their applications, with special emphasis on the attempts to obtain biological effects of these potentially important tools. What emerges is that the current state of the research is encouraging, and that these molecules are already useful in some biotechnology applications.