Applied Antisense Oligonucleotide Technology

Applied Antisense Oligonucleotide Technology provides the basic concepts as well as the practical concerns associated with the use of antisense oligonucleotides to modify gene expression. Chapters include oligonucleotide chemistry, DNA triplex formation, delivery mechanisms, pharmocokinetics, toxicity, oligonucleotides.

Cy A. Stein is the editor of Applied Antisense Oligonucleotide Technology, published by Wiley. Arthur M. Krieg is the editor of Applied Antisense Oligonucleotide Technology, published by Wiley.

PREFACE

ix

(1)

CONTRIBUTORS

x

I CHEMISTRY, OLD AND NEW

1

(108)

1 OLIGONUCLEOSIDE METHYLPHOSPHONATES: SYNTHESIS AND PROPERTIES

3

(20)

Paul S. Miller

2 OLIGO(NUCLEOSIDE PHOSPHOROTHIOATE)S

23

(28)

Piotr Guga

Maria Koziolkiewicz

Andrzej Okruszek

Wojciech J. Stec

3 MODIFIED OLIGODEOXYNUCLEOTIDES AS ANTISENSE THERAPEUTICS

51

(22)

Peter H. Seeberger

Marvin H. Caruthers

4 NOVEL CHEMISTRY

73

(36)

Karl-Heinz Altmann

Bernard Cuenoud

Peter Von Matt

II OLIGONUCLEOTIDE INTERNALIZATION, MECHANISM OF ACTION, AND NON-SEQUENCE SPECIFICITY

109

(64)

5 CELLULAR UPTAKE AND BIODISTRIBUTION OF OLIGODEOXYNUCLEOTIDES

111

(18)

Basil Hanss

C.A. Stein

Paul E. Klotman

6 USE OF CATIONIC LIPID COMPLEXES FOR ANTISENSE OLIGONUCLEOTIDE DELIVERY

129

(18)

C. Frank Bennett

7 NONANTISENSE EFFECTS OF ANTISENSE OLIGONUCLEOTIDES

147

(14)

Leonard M. Neckers

Kanak Iyer

8 RIBONUCLEASE H-MEDIATED ANTISENSE EFFECTS OF OLIGONUCLEOTIDES AND CONTROLS FOR ANTISENSE EXPERIMENTS

161

(12)

David M. Tidd

III.A SEQUENCE-SPECIFIC INHIBITION OF GENE EXPRESSION

173

(124)

9 THE DEVELOPMENT OF C-5 PROPYNE OLIGONUCLEOTIDES AS INHIBITORS OF GENE FUNCTION

175

(18)

W. Michael Flanagan

Richard W. Wagner

10 THE USE OF ANTISENSE OLIGONUCLEOTIDES TO INHIBIT EXPRESSION OF ISOZYMES OF PROTEIN KINASE C

193

(14)

Nicholas M. Dean

Lemonidis, K.

McKay, R.

Miraglia, L.

Trent, K.

Pribble, J.P.

11 BCR-ABL AS A TARGET FOR ANTISENSE INTERVENTION

207

(24)

Stephen G. O'Brien

Toon F.C.M. Smetsers

12 THE NF-kB TRANSCRIPTION FACTOR

231

(14)

Ramaswamy Narayanan

13 DISRUPTION OF THE MAP KINASE SIGNALING PATHWAY USING ANTISENSE OLIGONUCLEOTIDE INHIBITORS TARGETED TO RAS AND RAF KINASE

245

(18)

Brett P. Monia

14 PROTEIN KINASE A-DIRECTED ANTISENSE BLOCKADE OF CANCER GROWTH: SINGLE GENE-BASED THERAPEUTIC APPROACH

263

(20)

Yoon S. Cho-Chung

15 USE OF ANTISENSE OLIGONUCLEOTIDES IN THE CENTRAL NERVOUS SYSTEM: WHY SUCH SUCCESS?

283

(14)

Margaret M. McCarthy

III.B APPLIED ANTISENSE OLIGONUCLEOTIDE THERAPEUTICS

297

(56)

16 PERTURBING HEMATOPOIETIC CELL GENE EXPRESSION WITH OLIGODEOXYNUCLEOTIDES: RESEARCH AND CLINICAL APPLICATIONS

299

(18)

Alan M. Gewirtz

Mariusz Z. Ratajczak

17 BCL2

317

(18)

Burkhard Jansen

Bob D. Brown

18 BIOLOGICAL ACTIVITY OF GUANOSINE QUARTET-FORMING OLIGONUCLEOTIDES

335

(18)

Robert F. Rando

Michael E. Hogan

IV OLIGONUCLEOTIDES AS ANTI-HIV AGENTS

353

(42)

19 PERSPECTIVES ON ANTISENSE TECHNOLOGY AGAINST HIV

355

(10)

Jay E. Gee

Amelie Benoit de Coignac

Ian Robbins

Bernard LeBleu

20 IN VIVO PHARMACOKINETICS OF OLIGONUCLEOTIDES

365

(22)

Sudhir Agrawal

21 EARLY CLINICAL TRIALS WITH GEM 91, A SYSTEMIC OLIGODEOXYNUCLEOTIDE

387

(8)

R. Russell Martin

V THERAPEUTIC OLIGONUCLEOTIDE DATA BASE: PHARMACOKINETICS, IMMUNE STIMULATION, AND USE AS ANTIRESTENOTIC AGENTS

395

(54)

22 ANTISENSE THERAPY TO INHIBIT ANGIOPLASTY RESTENOSIS

397

(10)

Leroy E. Rabbani

Weizheng Wang

23 PHARMACOKINETICS OF OLIGONUCLEOTIDES: A REVIEW OF CURRENT KNOWLEDGE AND ISSUES FOR THE FUTURE

407

(24)

Thomas L. Wallace

Paul A. Cossum

24 LEUKOCYTE STIMULATION BY OLIGODEOXYNUCLEOTIDES

431

(18)

Arthur M. Krieg

VI SELECTED OLIGODEOXYNUCLEOTIDE DEVELOPMENTAL TOPICS: SPLICING AND TRIPLEXES

449

(60)

25 MODIFICATION OF ALTERNATIVE SPLICING OF PRE-mRNA BY ANTISENSE OLIGONUCLEOTIDES

451

(20)

Ryszard Kole

26 GENE-TARGETED TRIPLE-HELIX-FORMING OLIGONUCLEOTIDES

471

(16)

Fedor Svinarchuk

Claude Malvy

27 TRIPLEX-FORMING OLIGONUCLEOTIDES FOR GENETIC MANIPULATION: AN ALTERNATIVE VIEW

487

(22)

A. Fawad Faruqi

Peter M. Glazer

VII A REVIEW OF RIBOZYME TECHNOLOGY

509

(18)

28 THERAPEUTIC RIBOZYMES: PRINCIPLES, APPLICATIONS, AND PROBLEMS

511

(16)

John J. Rossi

INDEX

527

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Applied Antisense Oligonucleotide Technology

Summary

Author Biography

Table of Contents

Supplemental Materials