Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/7487
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dc.contributor.authorAnson, D.en
dc.contributor.authorFuller, M.en
dc.date.issued2003en
dc.identifier.citationJournal of Gene Medicine, 2003; 5(10):829-838en
dc.identifier.issn1099-498Xen
dc.identifier.issn1521-2254en
dc.identifier.urihttp://hdl.handle.net/2440/7487-
dc.description.abstractHIV-1 provides an attractive option as the basis for gene transfer vectors due to its ability to stably transduce non-cycling cell populations. In order to fully utilise the promise of HIV-1 as a vector it is important that the effects of viral cis sequence elements on vector function are carefully delineated.In this study we have systematically evaluated the effect of various cis elements from the HIV-1 YU-2 genome that have been implicated as either affecting vector performance, or HIV-1 replication, on the efficiency of vector production (titre and infectivity). As a measure of the relative safety of vectors their propensity to inadvertently transfer the gagpol gene to transduced cells was assessed.Sequences that were found to increase vector titre were from the 5' end of the gag gene, from the 5' and 3' ends of the env gene, from immediately upstream of the polypurine tract, and the central polypurine tract. The substitution of the HIV-1 RRE with heterologous RNA transport elements, or the deletion of the RRE, resulted in greatly reduced vector titres. RNA analysis suggested that the role of the Rev/RRE system extends beyond simply acting as an RNA nuclear export signal. The relative safety of different vector designs was compared and an optimal construct selected.Based on our results we have constructed a vector that is both more efficient, and has better safety characteristics, than the widely used pHR' HIV-1 vector construct.en
dc.language.isoenen
dc.publisherJohn Wiley & Sons Ltden
dc.subjectNIH 3T3 Cells; Animals; Mice; HIV-1; Gene Transfer Techniques; Mutagenesis; Genes, rev; Genes, env; Genes, gag; Genetic Vectors; Plasmids; Genetic Therapyen
dc.titleRational development of a HIV-1 gene therapy vectoren
dc.typeJournal articleen
dc.identifier.rmid0020030948en
dc.identifier.doi10.1002/jgm.415en
dc.identifier.pubid58505-
pubs.library.collectionPaediatrics publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
Appears in Collections:Paediatrics publications

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