Nucleic Acid Therapeutics in Cancer

217 Pages·2004·5.462 MB·English

by  Fritz Eckstein PhD (auth.), Alan M. Gewirtz MD (eds.)

NUCLEIC ACID THERAPEUTICS IN CANCER
CANCER DRUG DISCOVERY
AND DEVELOPMENT
BEVERLY A. TEICHER, SERIES EDITOR
Proteasome Inhibitors in Cancer Therapy, Tumor Targeting in Cancer Therapy, edited
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Nucleic Acid Therapeutics in Cancer, edited Hormone Therapy in Breast and Prostate
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Promising Cancer Chemopreventive Tumor Models in Cancer Research, edited by
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Platinum-Based Drugs in Cancer Therapy,
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Handbook of Anticancer Pharmacokinetics edited by Lloyd R. Kelland and Nicholas
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NUCLEICACID
THERAPEUTICS IN CANCER
Edited by
ArAN M.
GEWIRTZ, MD
Department ofI nternal Medicine,
University ofP ennsylvania School ofM edicine,
Philadelphia, PA
*-
Springer Science+Business
7 ~ Media, LLC
ISBN 978-1-4684-9858-5 ISBN 978-1-59259-777-2 (eBook)
DOI 10.1007/978-1-59259-777-2
© 2004 Springer Seienee+Business Media New York
Originally published by Humana Press Ine. in 2004
Softeover reprint ofthe hardeover lst edition 2004
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Library of Congress Cataloging-in-Publieation Data
Nucleic acid therapeutics in cancer / edited by Alan M. Gewirtz.
p. ; em. -- (Cancer drug discovery and development)
Papers from a conference held Apr. 2000 in Bryn Mawr, Pa.
Includes bibliographical references and index.
1. Antisense nucleic acids--Therapeutie use. 2. Cancer--Chemotherapy.
[DNLM: 1. Neoplasms--therapy--Congresses.2. Gene
Therapy--methods--Congresses. 3. Nucleic Aeids--therapeutie
use--Congresses. QZ 267 N9638 2004] 1. Gewirtz, A. M. (Alan M.) II.
Series.
RC271.A69N83 2004
616.99'4061--dc22
2003025020
PREFACE
There is no impossibility that cannot be overcome.
-From Fateless by Imre Kertesz, Nobel Laureate in Literature, 2002
The development of simple, reliable tools for modifying gene expression "on
demand" has stoked the fires of the revolutionary advances being made, on
almost a daily basis, in cell and molecular biology. Similar advances are being
made in understanding the molecular pathogenesis of many diseases that effect
humankind. Not surprisingly, the wish to exploit these advances for the treat
ment of disease has grown in parallel.
My interest in molecular medicines led me into the field of nucleic acid thera
peutics some 15 years ago. Like any developing science, it has had its highs and
lows but overall, the movement has been inexorably in a positive direction. In
order to spur such progress on, I applied to the Leukemia and Lymphoma Society
of America for funds to sponsor a small, and highly focused workshop on basic
aspects related to the development of RNA-targeted therapeutics. Monies to
supplement the meeting were provided by the Doris Duke Charitable Foundation
and the Cancer Center at the University of Pennsylvania. This volume, Nucleic
Acid Therapeutics in Cancer, largely results from that meeting, which was held
in April of 2000 in Bryn Mawr, Pennsylvania.
This volume is small, as was the meeting, but all of the important issues, at
least as I view them, are covered in a succinct and highly readable form. These
include chapters on RNA biology and the underpinnings of what we now know
as RNA interference, oligodeoxynucleotide delivery into cells, strategies for
targeting these molecules to accessible regions with the mRNA, and some
examples of how these compounds are being used clinically. As such, the col
lected works should be of use to those who would like an introduction to this
field, and present state of the art.
It is my sincere belief that development of effectively targeted, and efficiently
delivered, nucleic acid molecules will lead to important advances in the diagno
sis and treatment of human malignancies. As was true for the field of monoclonal
antibody-based therapies, where hype was followed by disappointment and then
finally genuine triumph of the concept, I believe that breakthroughs in the area
of nucleic acid-mediated gene silencing will shortly be forthcoming and will
more than justify the time and resources expended in developing the therapeutic
use of these molecules.
Alan M. Gewirtz, MD
v
CONTENTS
Preface ............................................................................................................... v
Contributors ...................................................................................................... ix
Part I. Introduction and Perspective
1 Antisense Methodology: An Assessment After 25 Years ........................ 3
Fritz Eckstein
2 Nucleic Acid Therapeutics: An Introduction ........................................ 15
Alan M. Gewirtz
Part II. Basic Methodology
3 Targeted Genome Modification Via Triple Helix Formation .............. 27
Faye A. Rogers and Peter M. Glazer
4 Therapeutic Applications of Ribozymes ............................................... 45
John J. Rossi
5 Use of Catalytic DNA in Target Validation and Therapeutics ............ 65
Lun-Quan Sun
6 Targeted Destruction of Small, Stable RNAs:
Principles Applicable to Antisense Therapies .................................. 81
David A. Dunbar and Susan J. Baserga
7 Mechanism of Action of Antisense RNA in Eukaryotic Cells ............. 89
Zuo Zhang and Gordon G. Carmichael
Part III. Delivery
8 The Transport of Oligonucleotides Into Cells .................................... 107
R.L.Juliano
9 Peptide-Mediated Delivery of Antisense Oligonucleotides
and Related Material ........................................................................ 115
Eric Vives, Jean Philippe Richard, and Bernard Lebleu
10 Molecular Vectors for Gene Delivery to Cancer Cells ...................... 129
Guy Zuber, Jean-Serge Remy, Patrick Erbacher,
Pascale Belguise, and Jean-Paul Behr
Part IV. Targeting
11 Considerations on the Design of Antisense Oligonucleotides ........... 143
Rosel Kretschmer-Kazemi Far, Jens M. Warnecke,
and Georg Sczakiel
vii
viii Contents
12 Identification of Hybridization Accessible Sequence
in Messenger RNA ........................................................................... 155
Lida K. Gifford, Ponzy Lu, and Alan M. Gewirtz
Part V. Clinical Targets
13 Nucleic Acids As Gene Targeting Therapeutics ............................... 167
Joanna B. Opalinska and Susan E. Shetzline
14 L Y900003 (Isis 3521) and G3139 (Genasense; Oblimersen):
Phosphorothioate Antisense Oligonucleotides With Pleiotropic
Mechanisms of Action ...................................................................... 177
C. A. Stein, Nathalie Dias, Luba Benimetskaya, Jan S. Jepsen,
Johnathan C. H. Lai, and Anthony J. Raffo
15 Antisense Protein Kinase A-RIa Restores Normal Signal
Transduction Signatures to Inhibit Tumor Growth ......................... 199
Yoon S. Cho-Chung
Index .............................................................................................................. 213
CONTRIBUTORS
SUSAN J. BASERGA, MD, PhD • Departments of Molecular Biophysics
and Biochemistry, and Therapeutic Radiology and Genetics, Yale School
of Medicine, New Haven, CT
JEAN-PAUL BEHR, PhD • Laboratoire de Chimie Genetique Associe CNRS,
Faculte de Pharmacie, Universite Louis Pasteur de Strasbourg, Illkirch,
France
PASCALE BELGUISE, PhD • Laboratoire de Chimie Genetique Associe CNRS,
Faculte de Pharmacie, Universite Louis Pasteur de Strasbourg, Illkirch,
France
LUBA BENIMETSKA Y A, PhD • Department of Medicine, Albert Einstein College
of Medicine, Bronx, NY
GORDON G. CARMICHAEL, PhD • Department of Genetics and Developmental
Biology, University of Connecticut Health Center, Farmington, CT
YOON S. CHO-CHUNG, MD, PhD • Cellular Biochemistry Section, National
Cancer Institute, Bethesda, MD
NATHALIE DIAS, PhD • American Language Program, College of Physicians
and Surgeons, Columbia University, New York, NY
DAVID A. DUNBAR, PhD· Science Department, Cabrini College, Radnor, PA
FRITZ ECKSTEIN, PhD • Max-Planck-Institute for Experimental Medicine,
Gottingen, Germany
PATRICK ERBACHER, PhD· Laboratoire de Chimie Genetique Associe CNRS,
Faculte de Pharmacie, Universite Louis Pasteur de Strasbourg, Illkirch,
France
ALAN M. GEWIRTZ, MD· Department of Internal Medicine, University
of Pennsylvania School of Medicine, Philadelphia PA
LIDA K. GIFFORD, PhD • Department of Chemistry, University of Pennsylvania,
Philadelphia PA
PETER M. GLAZER, MD, PhD· Departments of Therapeutic Radiology
and Genetics, Yale University School of Medicine, New Haven, CT
JAN S. JEPSEN, BS • Danish Cancer Society, Copenhagen, Denmark
R. L. JULIANO, PhD • Department of Pharmacology, School of Medicine,
University of North Carolina, Chapel Hill, NC
ix
x Contributors
ROSEL KRETSCHMER-KAZEMI FAR, PhD· Institute for Molecular Medicine,
University of Lubeck, Lubeck, Germany
JOHNATHAN C. H. LAI, BS • Department of Biomedical Engineering, College
of Physicians and Surgeons, Columbia University, New York, NY
BERNARD LEBLEU, PhD • UMR5I24 CNRS, Institut de Genetique Moleculaire,
Universite de Montpellier II, Montpellier, France
PONZY Lu, PhD • Department of Chemistry, University of Pennsylvania,
Philadelphia PA
JOANNA B. OPALINSKA, MD • Department of Hematology, Pommeranian
Academy of Medicine, Szcecin, Poland
ANTHONY J. RAFFO, PhD • Department of Medicine, College of Physicians
and Surgeons, Columbia University, New York, NY
JEAN-SERGE REMY, PhD • Laboratoire de Chimie Genetique Associe CNRS,
Faculte de Pharmacie, Universite Louis Pasteur de Strasbourg, Illkirch,
France
JEAN PHILIPPE RICHARD, MSC • UMR5I24 CNRS, Institut de Genetique
Moleculaire, Universite de Montpellier II, Montpellier, France
FAYE A. ROGERS, PhD· Departments of Therapeutic Radiology and Genetics,
Yale University School of Medicine, New Haven, CT
JOHN J. ROSSI, PhD • Division of Molecular Biology, Beckman Research
Institute of the City of Hope, Duarte, CA
GEORG SCZAKIEL, PhD • Institute for Molecular Medicine, University
of Lubeck, Lubeck, Germany
SUSAN E. SHETZLINE, PhD • Department of Medicine, University
of Pennsylvania School of Medicine, Philadelphia, PA
C. A. STEIN, MD, PhD • Department of Medical Oncology/Medicine,
Albert Einstein College of Medicine, Bronx, NY
LUN-QUAN SUN, PhD • Johnson & Johnson Research Laboratories, Sydney,
Australia
ERIC VIVES, PhD • UMR5I24 CNRS, Institut de Genetique Moleculaire,
Universite de Montpellier II, Montpellier, France
JENS M. WARNECKE, PhD • Institute for Molecular Medicine, University
of Lubeck, Lubeck, Germany
ZUO ZHANG, PhD • Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
GUY ZUBER, PhD • Laboratoire de Chimie Genetique Associe CNRS,
Faculte de Pharmacie, Universite Louis Pasteur de Strasbourg, Illkirch,
France
I
INTRODUCTION AND PERSPECTIVE