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Prem Seth Adenoviruses: Basic Biology to Gene Therapy MEDICAL INTELLIGENCE UNIT 15 Prem Seth Adenoviruses: Basic Biology to Gene Therapy R.G. LANDES COMPANY MEDICAL INTELLIGENCE UNIT 15 Adenoviruses: Basic Biology to Gene Therapy Prem Seth, Ph.D. Human Gene Therapy Research Institute Des Moines, Iowa, U.S.A. and Medicine Branch National Cancer Institute National Institutes of Health Bethesda, Maryland, U.S.A. R.G. LANDES COMPANY AUSTIN, TEXAS U.S.A. MEDICAL INTELLIGENCE UNIT Adenoviruses: Basic Biology to Gene Therapy R.G. LANDES COMPANY Austin, Texas, U.S.A. Copyright ©1999 R.G. Landes Company All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Printed in the U.S.A. Please address all inquiries to the Publishers: R.G. Landes Company, 810 South Church Street, Georgetown, Texas, U.S.A. 78626 Phone: 512/ 863 7762; FAX: 512/ 863 0081 ISBN: 1-57059-584-4 While the authors, editors and publisher believe that drug selection and dosage and the specifica- tions and usage of equipment and devices, as set forth in this book, are in accord with current recommendations and practice at the time of publication, they make no warranty, expressed or implied, with respect to material described in this book. In view of the ongoing research, equipment development, changes in governmental regulations and the rapid accumulation of information relating to the biomedical sciences, the reader is urged to carefully review and evaluate the informa- tion provided herein. Library of Congress Cataloging-in-Publication Data Adenoviruses: basic biology to gene therapy / [edited by] Prem Seth. p. cm. -- (Medical intelligence unit) Includes bibliographical references and index ISBN 1-57059-584-4(alk. paper) 1. Adenoviruses. 2. Genetic vectors. 3. Gene therapy. I. Seth, Prem, II. Series. [DNLM: 1. Adenoviridae. 2. Gene Therapy -- methods. 3. Genetic Vectors. QW 165.5.A3 A2323 1999] QR396.A343 1999 579.2'443 -- dc21 DNLM/DLC 99-32566 for Library of Congress CIP PUBLISHER’S NOTE Landes Bioscience produces books in six Intelligence Unit series: Medical, Molecular Biology, Neuroscience, Tissue Engineering, Biotechnology and Environmental. The authors of our books are acknowledged leaders in their fields. Topics are unique; almost without exception, no similar books exist on these topics. Our goal is to publish books in important and rapidly changing areas of bioscience for sophisticated researchers and clinicians. To achieve this goal, we have accelerated our publishing program to conform to the fast pace at which information grows in bioscience. Most of our books are published within 90 to 120 days of receipt of the manuscript. We would like to thank our readers for their continuing interest and welcome any comments or suggestions they may have for future books. Michelle Wamsley Production Manager R.G. Landes Company CONTENTS Section I: Discovery and Structure of Adenoviruses 1. Discovery and Classification of Adenoviruses ........................................ 1 Harold S. Ginsberg Discovery of Adenoviruses ...................................................................... 1 Classification ............................................................................................ 2 2. Adenovirus Capsid Proteins ..................................................................... 5 John J. Rux and Roger M. Burnett Virion Architecture ................................................................................. 5 Major Coat Proteins ................................................................................ 7 Minor Coat Proteins.............................................................................. 14 Future Directions................................................................................... 15 3. Organization of the Adenoviral Genome............................................... 17 Jane Flint Organization of Coding Sequences ...................................................... 18 Other Important Features ..................................................................... 26 Sequences That Fulfill Multiple Functions .......................................... 27 Conclusion ............................................................................................. 27 Section II: Adenovirus Life Cycle 4. Entry of Adenovirus into Cells ............................................................... 31 Prem Seth Binding of Adenovirus to the Cell Receptor, and its Entry into the Endosomes ........................................................................... 31 Adenovirus-Mediated Lysis of Endosome Membrane: Role of Low pH and Penton Base ..................................................... 33 Vectorial Movement of the Adenovirus into the Nucleus .................. 33 Conclusion ............................................................................................. 35 5. Early Gene Expression ............................................................................ 39 Philip E. Branton Adenovirus Genes and Products........................................................... 39 Early Region 1A (E1A) .......................................................................... 40 Regulation of Gene Expression by E1A Products ................................ 42 Early Region 1B (E1B) ........................................................................... 46 Early Region 2 (E2)................................................................................ 50 VA RNA and Regulation of Protein Synthesis ..................................... 50 Early Region 3 (E3)................................................................................ 50 gp19K ..................................................................................................... 50 Early Region 4 (E4)................................................................................ 51 Adenoviruses and Adenoviral Products as Therapeutic Agents ......... 54 Conclusion ............................................................................................. 55 6. Adenovirus DNA Replication ................................................................. 59 Muralidhara Ramachandra and R. Padmanabhan Viral Genome and the Origin of DNA Replication ............................. 59 E2 Region and Its Regulation................................................................ 59 Viral Replication Proteins ..................................................................... 60 Cellular Factors Required for Replication............................................ 62 Initiation and Elongation of DNA Replication .................................... 63 Conclusion ............................................................................................. 65 7. Adenovirus Late Gene Expression .......................................................... 69 Julie Boyer and Gary Ketner Structure of the Late RNAs ................................................................... 69 Transcriptional Activation .................................................................... 72 Non-MLTU Late Proteins ..................................................................... 73 Regulation of Polyadenylation .............................................................. 73 Regulation of Splicing ........................................................................... 74 Nuclear Organization ............................................................................ 74 mRNA Export ........................................................................................ 75 Inhibition of Translation of Host mRNA ............................................ 76 Conclusion ............................................................................................. 76 8. Role of Endoprotease in Adenovirus Infection ..................................... 79 Joseph Weber 9. Adenovirus Assembly.............................................................................. 85 Susanne I. Schmid and Patrick Hearing Assembly Intermediates ........................................................................ 85 Incomplete Particles of Adenovirus ..................................................... 85 Polar Encapsidation of Adenovirus DNA ............................................ 86 Cis-acting Sequences Involved in Packaging Specificity ..................... 86 Trans-acting Components May Be Involved in Packaging ................. 88 Virus Release from Infected Cells ......................................................... 88 Section III: Adenoviral Vectors for Gene Therapy: Preclinical Research 10. Development of Adenoviral Vectors for Gene Therapy ....................... 91 Dai Katayose and Prem Seth Recombinant Adenoviral Vectors........................................................ 91 Adenovirally-Mediated Enhancement of DNA Delivery and the Concepts of Molecular Conjugates ..................................... 96 Conclusion ............................................................................................. 99 11. Adenoviral Vectors for Cancer Gene Therapy .................................... 103 Prem Seth, Yu Katayose, and Amol N.S. Rakkar Direct: Toxic Transgene Products ...................................................... 104 Indirect: Immunomodulation Through Recombinant Adenoviral Vectors .......................................................................... 111 Other Novel Strategies........................................................................
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