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University of Groningen Exogenous and endogenous gene regulation for specific and efficient cancer gene therapy Gommans, Willemijn Maria IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2006 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Gommans, W. M. (2006). Exogenous and endogenous gene regulation for specific and efficient cancer gene therapy s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 06-03-2018

Exogenous and endogenous gene regulation for specific and efficient cancer gene therapy Willemijn Gommans

Cover: Electron microscopy picture of adenoviruses. This picture was taken by Dr. J.M. Gommans nearly 35 years ago and modified by Mr. J.F. Laumans. ISBN printed version: 90-367-800-2 ISBN electronic version: 90-367-2801-0 2006 by W.M. Gommans All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means without permission of the author and the publisher holding the copyright of the published articles Page and cover design: Joel Laumans, Robert and Willemijn Gommans-Laumans Printed by: Gildeprint Drukkerijen te Enschede

RIJKSUNIVERSITEIT GRONINGEN Exogenous and endogenous gene regulation for specific and efficient cancer gene therapy Proefschrift ter verkrijging van het doctoraat in de Wiskunde en Natuurwetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op vrijdag 22 december 2006 om 16.15 uur door Willemijn Maria Gommans geboren op 26 augustus 1979 te Elst

Promotor: Copromotor: Prof. dr. H.J. Haisma Dr. M.G. Rots Beoordelingscommissie: Prof. dr. R.C. Hoeben Prof. dr. L.F.M.H. de Leij Dr. D.J. Segal

Paranimfen: Dorenda Oosterhuis Leonie Los The work presented in this thesis was performed at the department of Therapeutic Gene Modulation (University of Groningen, The Netherlands), which is part of the research school GUIDE. The printing of this thesis was financially supported by grants of: - Rijksuniversiteit Groningen - Groningen University Institute for Drug Exploration (GUIDE) - Harlan Nederland B.V. - Synvolux Therapeutics

Table of contents Chapter 1 General introduction and scope of this thesis 9 Chapter 2 Adenoviral gene therapy 21 Gommans et al, Encyclopedia of Diagnostic Genomics and Proteomics, 2005 Chapter 3 The carcinoma-specific Epithelial Glycoprotein-2 promoter 29 controls efficient and selective gene expression in an adenoviral context Gommans et al, Cancer Gene Ther. (2006) 13(2):150-8 Chapter 4 Highly efficient and carcinoma-specific adenoviral 47 replication restricted by the EGP-2 promoter Gommans et al, J Control Release, in press Chapter 5 Towards a double controlled conditionally replicative 67 adenovirus for potent and specific melanoma cell kill Chapter 6 Engineering zinc finger protein transcription factors: 75 The therapeutic relevance of switching endogenous gene expression on or off at command Gommans et al, J Mol Biol. (2005) 354(3):507-19 Chapter 7 Engineering zinc finger protein transcription factors 99 to down-regulate the epithelial glycoprotein-2 promoter as a novel anti-cancer treatment Gommans et al, Mol Carcinog., in press Chapter 8 Summary and general discussion 117 & Future perspectives and conclusion Chapter 9 Samenvatting 133 Gommans et al, Tijdschrift kanker. 2006: 30(4):26-29 Appendix: List of abbreviations Selected color figures Dankwoord Curriculum vitae