Lipoadenofection-mediated gene delivery to the corneal endothelium: prospects for modulating graft rejection

Transplantation
C V Arancibia-CárcamoA J George

Abstract

Gene transfer to the corneal endothelium has potential for the prevention or reversal of corneal allograft rejection. Previous work has examined adenoviral vectors for gene transfer to endothelium. These have a number of theoretical and practical disadvantages, both for experimental and clinical applications. We have therefore used lipoadenofection, in which plasmid DNA is delivered using a combination of liposomes and adenovirus, to transfer marker genes to the cornea. Corneas were obtained from New Zealand White rabbits and cultured ex vivo using standard conditions. The corneas were transfected using either lipofection or lipoadenofection with plasmids encoding marker genes. The efficiency of gene transfer and the location and kinetics of gene expression were determined. We also investigated the delivery of a gene construct containing an inducible promoter that is activated by tumor necrosis factor (TNF), to determine whether expression of the relevant genes could be controlled by exogenous factors such as cytokines. This study shows that gene expression is limited to the endothelium and that expression is transient. Furthermore, we have shown that expression of a gene controlled by an inducible promoter only occurs when TNF...Continue Reading

References

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Citations

Feb 6, 2002·The Journal of Gene Medicine·Kathleen Blair-ParksDavid A Dean
May 12, 2005·Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft·S C BeutelspacherM O McClure
Jun 16, 2005·Progress in Retinal and Eye Research·Rajiv R MohanSteven E Wilson
Apr 30, 1999·Neuromuscular Disorders : NMD·J M Howell
Jul 11, 2003·Progress in Retinal and Eye Research·Nancy C Joyce
Nov 27, 2001·Clinical & Experimental Ophthalmology·S KlebeK A Williams
May 19, 2004·Nucleic Acids Research·Maria ManuntaAndrew J T George
Nov 4, 2000·Transplantation·W J KingA J George
Jan 8, 2005·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Jorge OrtizAbhinav Humar
Oct 13, 2000·American Journal of Respiratory and Critical Care Medicine·A J GeorgeD F Larkin
Jul 20, 2002·Clinical Pharmacokinetics·Fatemeh Akhlaghi, Andrew K Trull
May 19, 2006·Expert Opinion on Biological Therapy·P H TanA J T George
Jul 22, 2006·Expert Opinion on Biological Therapy·Peng H TanChristopher L H Chan
May 5, 2007·Expert Opinion on Biological Therapy·Stefanos TheoharisPeng H Tan
Jul 23, 2004·Expert Opinion on Biological Therapy·Keryn A WilliamsDouglas J Coster
Apr 15, 2003·The Journal of Gene Medicine·P H TanA J T George
Nov 25, 2003·Eye·A S Jun, D F P Larkin
Nov 8, 2005·The British Journal of Surgery·P H TanA J T George
Mar 23, 2001·Ocular Immunology and Inflammation·P F Torres, A Kijlstra
Mar 22, 2001·Transplantation·P H TanA J George
Jun 9, 2005·Experimental Eye Research·Sven Christoph BeutelspacherMyra O McClure

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