Retargeting FX binding-ablated HAdV-5 to vascular cells by inclusion of the RGD-4C peptide in hexon hypervariable region 7 and the HI loop

Stacy Robertson, Alan L Parker, Carolyn Clarke, Margeret R Duffy, Raul Alba, Stuart A Nicklin, Andrew H Baker

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies have generated interest into the function of human adenovirus serotype 5 (HAd-V5) hexon: factor X (FX)-binding and subsequent hepatocyte transduction and interaction with the immune system. Here, we retargeted adenovirus serotype 5 vectors, ablated for FX interaction, by replacing amino acids in hexon HVR7 with RGD-4C or inserting the peptide into the fiber HI loop. These genetic modifications in the capsid were compatible with virus assembly, and could efficiently retarget transduction of the vector via the αvβ3/5 integrin-mediated pathway, but did not alter immune recognition by pre-existing human neutralising anti-HAdV-5 antibodies or by natural antibodies in mouse serum. Thus, FX-binding ablated HAdV-5 can be retargeted but remain sensitive to immune-mediated attack. These findings further refine HAd-V5 based vectors for human gene therapy and inform future vector development.

Original languageEnglish
JournalJournal of General Virology
Early online date16 May 2016
DOIs
Publication statusE-pub ahead of print - 16 May 2016

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