Lentivirus-mediated gene transfer to the rat, ovine and human cornea

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dc.contributor.authorParker, D.
dc.contributor.authorKaufmann, C.
dc.contributor.authorBrereton, H.
dc.contributor.authorAnson, D.
dc.contributor.authorFrancis-Staite, L.
dc.contributor.authorJessup, C.
dc.contributor.authorMarshall, K.
dc.contributor.authorTan, C.
dc.contributor.authorKoldej, R.
dc.contributor.authorCoster, D.
dc.contributor.authorWilliams, K.
dc.date.issued2007
dc.description© 2007 Nature Publishing Group. All rights reserved.
dc.description.abstractGene therapy of the cornea shows promise for modulating corneal transplant rejection but the most appropriate vector for gene transfer has yet to be determined. We investigated a lentiviral vector (LV) for its ability to transduce corneal endothelium. A lentivector expressing enhanced yellow fluorescent protein (eYFP) under the control of the Simian virus type 40 early promoter (LV-SV40-eYFP) transduced 80-90% of rat, ovine and human corneal endothelial cells as detected by fluorescence microscopy. The kinetics of gene expression varied among species, with ovine corneal endothelium showing a relative delay in detectable reporter gene expression compared with the rat or human corneal endothelium. Vectors containing the myeloproliferative sarcoma virus promoter or the phosphoglycerate kinase promoter were not significantly more effective than LV-SV40-eYFP. The stability of eYFP expression in rat and ovine corneas following ex vivo transduction of the donor cornea was assessed following orthotopic corneal transplantation. Following transduction ex vivo, eYFP expression was maintained in corneal endothelial cells for at least 28 days after corneal transplantation in the sheep and >60 days in the rat. Thus, rat, ovine and human corneal endothelial cells were efficiently transduced by the LV, and gene expression appeared stable over weeks in vivo.
dc.description.statementofresponsibilityD.G.A. Parker, C. Kaufmann, H.M. Brereton, D.S. Anson, L. Francis-Staite, C.F. Jessup, K. Marshall, C. Tan, R. Koldej, D.J. Coster and K.A. Williams
dc.identifier.citationGene Therapy, 2007; 14(9):760-767
dc.identifier.doi10.1038/sj.gt.3302921
dc.identifier.issn0969-7128
dc.identifier.issn1476-5462
dc.identifier.orcidJessup, C. [0000-0003-1184-6653]
dc.identifier.urihttp://hdl.handle.net/2440/57396
dc.language.isoen
dc.publisherNature Publishing Group
dc.source.urihttps://doi.org/10.1038/sj.gt.3302921
dc.subjectcorneal transplantation
dc.subjectcorneal endothelium
dc.subjectlentiviral vector
dc.titleLentivirus-mediated gene transfer to the rat, ovine and human cornea
dc.typeJournal article
pubs.publication-statusPublished

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