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AuthorCorjon, Stéphaniedc.contributor.author
Date of accession2016-03-14T15:22:32Zdc.date.accessioned
Available in OPARU since2016-03-14T15:22:32Zdc.date.available
Year of creation2008dc.date.created
AbstractAdenovirus (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.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (Fassung vom 03.05.2003)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v1dc.rights.uri
KeywordAdenovirus vectorsdc.subject
KeywordChemical modificationdc.subject
KeywordGene deliverydc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHAdenoviridaedc.subject.mesh
TitleTargeting of adenovirus gene transfer vectors via combined geneti-chemical modification of the minor capsid protein IXdc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-1481dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-65186dc.identifier.urn
GNDGen-Targetingdc.subject.gnd
GNDGentransferdc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
Date of activation2008-08-18T09:24:44Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionZ: J-H 11.966; W: W-H 11.450uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS ID6518uulm.vtsID
CategoryPublikationenuulm.category
Bibliographyuulmuulm.bibliographie


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