Synthetic Nucleic Acids as Inhibitors of Gene Expression: Mechanisms, Applications, and Therapeutic Implications

199 Pages·2004·3.49 MB·English

by  Levon Michael Khachigian (Editor)

Synthetic Nucleic
Acids as Inhibitors of
Gene Expression
Mechanisms, Applications, and
Therapeutic Implications

Synthetic Nucleic
Acids as Inhibitors of
Gene Expression
Mechanisms, Applications, and
Therapeutic Implications
Levon Michael Khachigian
Edited by
CRC PR ESS
Boca Raton London New York Washington, D.C.
Library of Congress Cataloging-in-Publication Data
Synthesis nucleic acids as inhibitors of gene expression: mechanisms, applications, and
therapeutic implications / edited by Levon Khachigian.
p. cm.
Includes bibliographical references and index.
ISBN 0-8493-3025-4 (alk. paper)
1. Catalytic RNA. 2. Repressors, Genetic. 3. Genetic regulation. I. Khachigian, Levon.
QP623.5.C36S966 2004
572.8—dc22
2004054474
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Preface
In the postgenomic era, we have at our fingertips complete genome sequences and
huge numbers of predicted gene sequences from a multitude of complex organisms.
There remains, however, the critical need to understand the functions of these gene
products to delineate the precise roles of these genes in complex biological milieu.
Synthetic nucleic acids are at the cutting-edge of molecular strategies that target
genes of interest in a specific and cost-effective manner. These agents are now being
used as new and exciting gene-silencing agents in vitro, in animal models of disease,
and in humans.
This book brings together timely authoritative, in-depth reviews by renowned
international leaders in the fields of ribozymes, RNA interference, DNAzymes and
oligonucleotide decoys, with emphasis on biochemistry and translational research.
No other book draws together these topics.
Sections by Nobura Fukuda (Chapter 1) and Mehdi Nosrati et al. (Chapter 2)
on ribozymes include an in-depth discussion of ribozyme subtypes (hammerhead,
chimeric, minizymes, maxizymes, zinzymes, group I introns), structure-functional
aspects including modifications, cellular delivery and therapeutic applications in
diseases such as cancer and cardiovascular disease.
McManus and Harfe’s (Chapter 3) section on RNA interference provides a
historical and mechanistic account of small interfering RNAs and microRNAs as
suppressors of gene expression.
Contributions by Steve Santoro (Chapter 4), Gail Mitchell Emilsson and Ron
Breaker (Chapter 5), Masaki Warashina et al. (Chapter 6), Akhil Banerjea et al.
(Chapter 7), Michael Eisbacher and Lun-Quan Sun (Chapter 8), and Levon Khachi-
gian (Chapter 9) provide a comprehensive discussion on DNAzymes, their various
subtypes, modifications, selection strategies, kinetics and biochemistry, cellular
delivery, applications in target validation, and diagnostic and therapeutic applications
in a diverse array of pathologies.
Finally, Ryuichi Morishita et al. (Chapter 10) discuss the mechanisms and
multiple therapeutic applications of double-stranded oligonucleotide decoys as non-
catalytic nucleic acid strategies specifically targeting transcription factors.
I am confident this book will serve as a valuable practical and informative
resource to basic and applied academic and industrial scientists alike.
Levon Khachigian
Sydney, Australia

About the Editor
Professor Levon Michael Khachigian (BSc[Hons], PhD,
DSc) is a Principal Research Fellow of the National Health
and Medical Research Council of Australia and Head of the
Transcription and Gene Targeting Laboratory at The Centre
for Vascular Research, University of New South Wales and
Prince of Wales Hospital, Sydney.
His research, encompassed in over 100 journal articles and
book chapters, has greatly increased our understanding of the
fundamental transcriptional mechanisms that lead to the inap-
propriate expression of harmful genes in cells of the artery wall. It has also led to
his generation of novel DNA-based drugs that block arterial renarrowing after
balloon angioplasty in a variety of experimental models. More recently, he has been
unravelling the mechanisms behind tumor growth control and other neovascular
pathologies by inhibiting angiogenesis.
Professor Khachigian has been a major contributor to the broader workings of
science on matters of policy, advocacy, consultancy, peer-review, mentorship, and
societal service. For example, he is National Executive Director and President-Elect
of the Australian Society for Medical Research and former President of the Australian
Vascular Biology Society. He has served on numerous grant review, fellowship, and
policy formulation panels for the National Health and Medical Research Council of
Australia and the National Heart Foundation of Australia. He sits on the Editorial
Boards of five international journals.
Professor Khachigian has won many highly competitive awards for innovative
research including recently the Commonwealth Health Minister’s Award for Excel-
lence in Health and Medical Research, the Gottschalk Award from the Australian
Academy of Science, Eureka Prize for Scientific Research from the Australian
Museum, RT Hall Prize from the Cardiac Society of Australian and New Zealand,
AMGEN Medical Researcher Award, Eppendorf Award for the Young Australian
Researcher, Quantum Scientific Research Award, Young Tall Poppy Award, and
numerous named research awards for research excellence from the Heart Foundation
of Australia.
Professor Khachigian received his BSc with first class honors in biochemistry
and a PhD in cell and molecular biology from the University of New South Wales,
then studied transcriptional control in the Department of Pathology, Brigham and
Women’s Hospital, Harvard Medical School. In 2004, he was awarded a DSc in
vascular pathobiology and translational research from the University of New South
Wales.

Contributors
Akhil C. Banerjea, Ph.D. Ritu Goila, Ph.D.
Laboratory of Virology, National Laboratory of Virology, National
Institute of Immunology Institute of Immunology
New Delhi, India New Delhi, India
Ronald R. Breaker, Ph.D. Brian D. Harfe, Ph.D.
Department of Molecular, Cellular and Department of Molecular Genetics and
Developmental Biology, Yale Microbiology, University of Florida
University College of Medicine
New Haven, Connecticut Gainesville, Florida
Samitabh Chakraborti, Ph.D. Takeshi Imanishi, M.D.
Laboratory of Virology, National Graduate School of Pharmaceutical
Institute of Immunology Sciences, Osaka University
New Delhi, India Osaka, Japan
Bipin C. Dash, Ph.D. Mohammed Kashani-Sabet, M.D.
Laboratory of Virology, National Cancer Center and Department of
Institute of Immunology Dermatology, University of
New Delhi, India California–San Francisco
San Francisco, California
Michael Eisbacher, Ph.D.
Levon M. Khachigian, Ph.D., D.Sc.
Johnson & Johnson Research Pty. Ltd.
Centre for Vascular Research,
Sydney, Australia
University of New South Wales
Department of Haematology, Prince of
Gail Mitchell Emilsson, Ph.D.
Wales Hospital
Department of Molecular, Cellular and
Sydney, Australia
Developmental Biology, Yale
University
Tomoko Kuwabara, M.D.
New Haven, Connecticut
Gene Discovery Research Center,
National Institute of Advanced
Noboru Fukuda, M.D., Ph.D.
Industrial Science and Technology
Second Department of Internal
(AIST)
Medicine, and Division of Cell
Higashi, Japan
Regeneration and Transplantation
Advanced Medical Research Centre
Michael T. McManus, Ph.D.
Nihon University School of Medicine
Massachusetts Institute of Technology
Tokyo, Japan
Cambridge, Massachusetts