FU Berlin Digitale Dissertation
Ulrike Siemetzki : Generation of a novel Doxycycline-controlled adenoviral vector-system for regulation of viral replication - new aspects in cancer gene therapy Entwicklung und Evaluierung eines Doxyzyklin-abhängigen adenoviralen Vektor-Replikations-Systems für den Einsatz in der Tumorgentherapie
|Abstract| |Table of Contents| |More Information|

Abstract Restricted replication competent adenoviral vectors (RRCA) for human cancer gene therapy have been investigated extensively for the last few years. Through their tumor selective induction of cell lysis and through the transduction of tumor tissue by viral replication they are very prospective for treating malignant alterations. Furthermore their ability for transcomplementation serves the possibility to elevate the expression level of a co-applicated replication deficient adenoviral vector at a therapeutic relevant intensity. So far there exist two strategies to target the viral replication to the tumor tissue: (i) deletions within the adenoviral E1 region, which hinder the replication in normal tissue and (ii) the use of tumor- or cell-specific promotors to control the E1A and/or the E1B region. Even though several in vitro studies demonstrated the selective vector replication as well as in vivo experiments exhibit a suppression of tumor growth, most of the investigators did not enter into the question after the replication of the RRCA in the surrounding tissue in vivo, so that this issue was leaved unanswered generally. Upon the relevance of RRCAs for the tumor gene therapy and the lacking knowledge about a system which makes the regulation of viral replication possible and which additionally prevent alterations in the surrounding tissue, this project yields to edit/process following issues: 1. the effective use of the positive features of already existing replication competent adenoviruses (RCA) in tumor gene therapy 2. the generation of a new vector system which makes the extern pharmacological regulation of adenoviral replication possible 3. investigations on the effectiveness of tumor cell lysis mediated by the new generated system 4. investigations on the protection against adenoviral replication in healthy cells through the tissue selective expression of the tetracycline-controlled transcriptional silencer (tTS)

Table of Contents Download the whole PhDthesis as a zip-tar file or as zip-File For download in PDF format click the chapter title Titelblatt, Inhaltsverzeichnis, Lebenslauf 1. Einleitung 2. Literaturýbersicht 3. Material und Methoden 4.1 Ergebnisse Teil 1 4.2 Ergebnisse Teil 2 5. Diskussion 6. Zusammenfassung / Summary 7. Anhang Literaturverzeichnis

More Information:
Online available:	http://www.diss.fu-berlin.de/2002/305/indexe.html
Language of PhDThesis:	german
Keywords:	Plasmid Vectors; Viral Replication; Cancer; Gene Therapy
DNB-Sachgruppe:	34 Veterinärmedizin
Date of disputation:	06-Dec-2002
PhDThesis from:	Fachbereich Veterinärmedizin, Freie Universität Berlin
First Referee:	Univ.-Prof. Dr. H. Ludwig
Second Referee:	Univ.-Prof. Dr. W. Poller
Third Referee:	Univ.-Prof. Dr. D. Ebner
Contact (Advisor):	ulisiemetzki@t-online.de
Date created:	12-Jan-2003
Date available:	17-Jan-2003

 

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