Gene Therapy for Renal Diseases and Transplantation

Transcription

1 Gene Therapy for Renal Diseases and Transplantation

2 Contributions to Nephrology Vol. 159 Series Editor Claudio Ronco Vicenza

3 Gene Therapy for Renal Diseases and Transplantation Volume Editors Ariela Benigni Bergamo Giuseppe Remuzzi Bergamo 15 figures, 4 in color, and 6 tables, 2008 Basel Freiburg Paris London New York Bangalore Bangkok Shanghai Singapore Tokyo Sydney

4 Contributions to Nephrology (Founded 1975 by Geoffrey M. Berlyne) Ariela Benigni Giuseppe Remuzzi Department of Molecular Medicine Mario Negri Institute Mario Negri Institute for Pharmacological Research for Pharmacological Research Via Gavazzeni, 11 Via Gavazzeni, 11 IT Bergamo (Italy) IT Bergamo (Italy) Library of Congress Cataloging-in-Publication Data Gene therapy for renal diseases and transplantation / volume editors, Ariela Benigni, Giuseppe Remuzzi. p. ; cm. (Contributions to nephrology, ISSN ; v. 159) Includes bibliographical references and indexes. ISBN (hard cover : alk. paper) 1. Kidneys Diseases Gene therapy. 2. Kidneys Transplantation Genetic aspects. 3. Graft rejection Prevention. 4. Gene therapy. I. Benigni, Ariela. II. Remuzzi, Giuseppe. III. Series. [DNLM: 1. Kidney Diseases therapy. 2. Gene Therapy. 3. Graft Rejection therapy. 4. Kidney Transplantation. W1 CO778UN v / WJ 300 G ] RC903.G dc Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents and Index Medicus. Disclaimer. The statements, options and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Copyright 2008 by S. Karger AG, P.O. Box, CH 4009 Basel (Switzerland) Printed in Switzerland on acid-free and non-aging paper (ISO 9706) by Reinhardt Druck, Basel ISSN ISBN

5 Contents VII Preface Benigni, A.; Remuzzi, G. (Bergamo) 1 Renal Diseases as Targets of Gene Therapy Phillips, B.; Giannoukakis, N.; Trucco, M. (Pittsburgh, Pa.) 13 Nonviral Gene Delivery Akita, H.; Harashima, H. (Sapporo/Saitama) 30 Retrovirus Vectors Lech, P.; Somia, N.V. (Minneapolis, Minn.) 47 Adenovirus Vectors for Renal-Targeted Gene Delivery Appledorn, D.M.; Seregin, S.; Amalfitano, A. (East Lansing, Mich.) 63 Adeno-Associated Virus Vectors: Versatile Tools for in vivo Gene Transfer Zentilin, L.; Giacca, M. (Trieste) 78 RNA Interference in Research and Therapy of Renal Diseases Rácz, Z.; Hamar, P. (Budapest) 96 Gene Therapy for Acute Renal Failure Torras, J.; Cruzado, J.M.; Herrero-Fresneda, I.; Grinyo, J.M. (Barcelona) 109 Chronic Deteriorating Renal Function and Renal Fibrosis Isaka, Y.; Takahara, S.; Imai, E. (Suita) V

6 122 Allograft Rejection: Acute and Chronic Studies Tomasoni, S.; Remuzzi, G.; Benigni, A. (Bergamo) 135 Gene Therapy for Renal Cancer Haviv, Y.S. (Jerusalem); Curiel, D.T. (Birmingham, Ala.) 151 HIV-Associated Nephropathy Wyatt, C.M.; Rosenstiel, P.E.; Klotman, P.E. (New York, N.Y.) 162 Author Index 163 Subject Index Contents VI

7 Preface Gene therapy holds promise for treatment of renal pathologies and for preventing renal allograft rejection. Initially conceived as a strategy to correct inherited genetic disorders, in the last decade gene therapy has been successfully applied to ameliorate the renal function compromised by progressive renal diseases and to prevent kidney allograft rejection in experimental animals. The success of transferring a gene into target renal cells essentially depends on the delivery system used. In the present book, a group of world experts in the field have provided new insights into viral and nonviral systems currently used to perform gene delivery. A chapter has been dedicated to the new field of RNA interference (RNAi). The potential of RNAi in research and therapeutics has been honoured by awarding the 2006 Nobel Prize in Medicine to Craig C. Mello and Andrew Z. Fire. Despite several obstacles still to overcome, RNAi-mediated gene transfer has already reached the clinics especially to treat age-related macular degeneration, preeclampsia and chronic myeloid leukemia. Renal ischemiareperfusion injury, which is the leading cause of acute renal failure after surgery, trauma and transplantation could be a possible area of application. Thanks to the progressive understanding of the cellular and molecular mechanisms, gene therapy might represent in the near future a new strategy to target molecules involved in tissue damage and in inflammation processes at the basis of ARF. Progressive renal diseases are characterized by chronic deterioration of the renal function and by renal fibrosis. Experimental glomerulonephritis and interstitial fibrosis have been successfully treated by gene transfer. However, before entering into the clinic, studies in larger animals are needed. Transplantation is the therapy of choice for many end-stage organ failure. Recipients of an organ VII

8 transplant take immunosuppressive drugs all their lives which exposes them to a great risk of developing opportunistic infections and cancer. Furthermore, current antirejection drugs are still inadequate to protect the graft from developing chronic rejection. Transfer of genes whose protein products have immunomodulatory properties proved to be beneficial in treating acute and chronic graft rejection. These studies represent the proof of principle that gene therapy may become a reality in clinical transplantation after demonstrating its efficacy in larger animals. Treatment of renal cancer and HIV-associated nephropathy could also benefit from a gene therapy strategy targeted to destroy cancer or infected cells. These aspects will be also discussed in the book. Ariela Benigni Giuseppe Remuzzi Preface VIII