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Targeting of adenovirus gene transfer vectors via combined geneti-chemical modification of the minor capsid protein IX

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196 Seiten
 
Veröffentlichung
2008-08-18
DOI
10.18725/OPARU-1481

Dissertation

Autoren
Corjon, Stéphanie
Fakultäten
Medizinische Fakultät
Lizenz
Standard (Fassung vom 03.05.2003)
https://oparu.uni-ulm.de/xmlui/license_v1
Zusammenfassung
Adenovirus (Ad) vectors have been widely used for gene delivery in vitro and in vivo, including in clinical trials. Safety and efficiency of Ad-mediated gene delivery would be increased if Ad vectors could be redirected to specific cell types. The main direction of the work described in this thesis was to evaluate different targeting strategies based on the attachment of specific receptor ligands to different capsid proteins, however with a focus on the minor capsid protein IX (pIX). Recently, in this laboratory, a new geneti-chemical targeting strategy was developed that is based on the genetic introduction of cysteine residues bearing reactive thiol groups into solvent-accessible capsomeres of the virion and subsequent chemical coupling of ligands. This technology was used to attach high-affinity ligands to pIX. In this study, we demonstrated (i) that the Receptor-Associated Protein (RAP) as a ligand can mediate efficient targeting to its cognate receptor when displayed on pIX, (ii) that pIX modification for targeting purposes requires dissociation of vector particle-ligand-receptor complexes after cell entry, and (iii) that the size of a ligand attached to pIX can be a critical parameter for successful targeting, (iv) that this geneti-chemical platform can be used for particle imaging in live cells and (v) that improved liver gene transfer can be achieved with Ad vectors carrying RAP attached to pIX. These findings indicate that in vivo targeting of Ad vectors via attachment of ligands to pIX is feasible. Therefore, reduction of vector dose for in vivo gene delivery is possible, resulting in improved safety.
Erstellung / Fertigstellung
2008
Normierte Schlagwörter
Gen-Targeting [GND]
Gentransfer [GND]
Adenoviridae [MeSH]
Schlagwörter
Adenovirus vectors; Chemical modification; Gene delivery
DDC-Sachgruppe
DDC 610 / Medicine & health

Metadata
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Zitiervorlage

Corjon, Stéphanie (2008): Targeting of adenovirus gene transfer vectors via combined geneti-chemical modification of the minor capsid protein IX. Open Access Repositorium der Universität Ulm. Dissertation. http://dx.doi.org/10.18725/OPARU-1481

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