Coagulation factor X mediates adenovirus type 5 liver gene transfer in non-human primates (Microcebus murinus)

Alba, R., Bradshaw, A.C. , Mestre-Francés, N., Verdier, J.-M., Henaff, D. and Baker, A.H. (2012) Coagulation factor X mediates adenovirus type 5 liver gene transfer in non-human primates (Microcebus murinus). Gene Therapy, 19(1), pp. 109-113. (doi: 10.1038/gt.2011.87)

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Publisher's URL: http://dx.doi.org/10.1038/gt.2011.87

Abstract

Coagulation factor X (FX)-binding ablated adenovirus type 5 (Ad5) vectors have been genetically engineered to ablate the interaction with FX, resulting in substantially reduced hepatocyte transduction following intravenous administration in rodents. Here, we quantify viral genomes and gene transfer mediated by Ad5 and FX-binding-ablated Ad5 vectors in non-human primates. Ad5 vectors accumulated in and mediated gene transfer predominantly to the liver, whereas FX-binding-ablated vectors primarily targeted the spleen but showed negligible liver gene transfer. In addition, we show that Ad5 binding to hepatocytes may be due to the presence of heparan sulfate proteoglycans (HSPGs) on the cell membrane. Therefore, the Ad5-FX-HSPG pathway mediating liver gene transfer in rodents is also the mechanism underlying Ad5 hepatocyte transduction in Microcebus murinus. Gene Therapy (2012) 19, 109-113; doi:10.1038/gt.2011.87; published online 16 June 2011

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew and Alba, Dr Raul and Bradshaw, Dr Angela
Authors: Alba, R., Bradshaw, A.C., Mestre-Francés, N., Verdier, J.-M., Henaff, D., and Baker, A.H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Gene Therapy
Publisher:Nature Publishing Group
ISSN:0969-7128
ISSN (Online):1476-5462
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
519431Interrogation and manipulation of miRNA in acute vascular injuryAndrew BakerBritish Heart Foundation (BHF)RG/09/005/27915RI CARDIOVASCULAR & MEDICAL SCIENCES