Robertson, S., Parker, A. L., Clarke, C., Duffy, M. R., Alba, R., Nicklin, S. A. and Baker, A. H. (2016) 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. Journal of General Virology, 97(8), pp. 1911-1916. (doi: 10.1099/jgv.0.000505) (PMID:27189759) (PMCID:PMC5156330)
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Abstract
Recent studies have generated interest in the function of human adenovirus serotype 5 (HAdV-5) 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 fibre 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 neutralizing 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 HAdV-5-based vectors for human gene therapy and inform future vector development.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Duffy, Ms Margaret and Nicklin, Professor Stuart and Clarke, Dr Carolyn and Alba, Dr Raul and Baker, Professor Andrew and Robertson, Dr Stacy |
| Authors: | Robertson, S., Parker, A. L., Clarke, C., Duffy, M. R., Alba, R., Nicklin, S. A., and Baker, A. H. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Journal of General Virology |
| Publisher: | Society for General Microbiology |
| ISSN: | 0022-1317 |
| ISSN (Online): | 1465-2099 |
| Copyright Holders: | Copyright © 2016 The Authors |
| First Published: | First published in Journal of General Virology 97(8): 1911-1916 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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