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.
journal_name
Gene Therjournal_title
Gene therapyauthors
Alba R,Bradshaw AC,Mestre-Francés N,Verdier JM,Henaff D,Baker AHdoi
10.1038/gt.2011.87subject
Has Abstractpub_date
2012-01-01 00:00:00pages
109-13issue
1eissn
0969-7128issn
1476-5462pii
gt201187journal_volume
19pub_type
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