E-selectin is a viable route of infection for polymer-coated adenovirus retargeting in TNF-α-activated human umbilical vein endothelial cells.
BACKGROUND: E-selectin is an attractive endothelial cell surface marker in inflammation and cancer. PURPOSE: We sought to investigate retargeting of adenovirus via E-selectin as a viable pathway of infection in tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelial cells (HUVECs)...
| Main Authors: | , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1797085795266330624 |
|---|---|
| author | Bachtarzi, H Stevenson, M Subr, V Seymour, L Fisher, K |
| author_facet | Bachtarzi, H Stevenson, M Subr, V Seymour, L Fisher, K |
| author_sort | Bachtarzi, H |
| collection | OXFORD |
| description | BACKGROUND: E-selectin is an attractive endothelial cell surface marker in inflammation and cancer. PURPOSE: We sought to investigate retargeting of adenovirus via E-selectin as a viable pathway of infection in tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelial cells (HUVECs). METHODS: E1, E3-deleted Ad5 expressing cytomegalovirus immediate-early (CMV IE) promoter-driven luciferase (Adluc) was coated with an amino-reactive multivalent hydrophilic polymer based on poly [N-(2-hydroxypropyl) methacrylamide] to generate pHPMA-adenovirus (pcAdluc). This was then retargeted by covalent attachment of a mouse antihuman E-selectin monoclonal antibody (MHES mAb), purified from the H18/7 hybridoma cell line (MHESpcAdluc). RESULTS: MHESpcAdluc was efficiently taken up into HUVECs, generating a high level of transduction in TNF-α-treated E-selectin positive cells but not in untreated receptor-negative cells. Specific retargeting of MHESpcAdluc was demonstrated through reduced transduction of stimulated HUVEC when incubated in the presence of free E-selectin antibodies. DISCUSSION AND CONCLUSION: Our results suggest that E-selectin could be a valuable target for gene transfer strategies internalizing polymer-coated modified adenovirus particles through a viable receptor-mediated endocytosis pathway, generating adequate levels of transgene expression per virus genome copy without compromising the specific activity of the parental virus. |
| first_indexed | 2024-03-07T02:13:02Z |
| format | Journal article |
| id | oxford-uuid:a14ecb07-c86b-49ff-8e12-410cbc8480ff |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:13:02Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:a14ecb07-c86b-49ff-8e12-410cbc8480ff2022-03-27T02:12:11ZE-selectin is a viable route of infection for polymer-coated adenovirus retargeting in TNF-α-activated human umbilical vein endothelial cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a14ecb07-c86b-49ff-8e12-410cbc8480ffEnglishSymplectic Elements at Oxford2011Bachtarzi, HStevenson, MSubr, VSeymour, LFisher, KBACKGROUND: E-selectin is an attractive endothelial cell surface marker in inflammation and cancer. PURPOSE: We sought to investigate retargeting of adenovirus via E-selectin as a viable pathway of infection in tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelial cells (HUVECs). METHODS: E1, E3-deleted Ad5 expressing cytomegalovirus immediate-early (CMV IE) promoter-driven luciferase (Adluc) was coated with an amino-reactive multivalent hydrophilic polymer based on poly [N-(2-hydroxypropyl) methacrylamide] to generate pHPMA-adenovirus (pcAdluc). This was then retargeted by covalent attachment of a mouse antihuman E-selectin monoclonal antibody (MHES mAb), purified from the H18/7 hybridoma cell line (MHESpcAdluc). RESULTS: MHESpcAdluc was efficiently taken up into HUVECs, generating a high level of transduction in TNF-α-treated E-selectin positive cells but not in untreated receptor-negative cells. Specific retargeting of MHESpcAdluc was demonstrated through reduced transduction of stimulated HUVEC when incubated in the presence of free E-selectin antibodies. DISCUSSION AND CONCLUSION: Our results suggest that E-selectin could be a valuable target for gene transfer strategies internalizing polymer-coated modified adenovirus particles through a viable receptor-mediated endocytosis pathway, generating adequate levels of transgene expression per virus genome copy without compromising the specific activity of the parental virus. |
| spellingShingle | Bachtarzi, H Stevenson, M Subr, V Seymour, L Fisher, K E-selectin is a viable route of infection for polymer-coated adenovirus retargeting in TNF-α-activated human umbilical vein endothelial cells. |
| title | E-selectin is a viable route of infection for polymer-coated adenovirus retargeting in TNF-α-activated human umbilical vein endothelial cells. |
| title_full | E-selectin is a viable route of infection for polymer-coated adenovirus retargeting in TNF-α-activated human umbilical vein endothelial cells. |
| title_fullStr | E-selectin is a viable route of infection for polymer-coated adenovirus retargeting in TNF-α-activated human umbilical vein endothelial cells. |
| title_full_unstemmed | E-selectin is a viable route of infection for polymer-coated adenovirus retargeting in TNF-α-activated human umbilical vein endothelial cells. |
| title_short | E-selectin is a viable route of infection for polymer-coated adenovirus retargeting in TNF-α-activated human umbilical vein endothelial cells. |
| title_sort | e selectin is a viable route of infection for polymer coated adenovirus retargeting in tnf α activated human umbilical vein endothelial cells |
| work_keys_str_mv | AT bachtarzih eselectinisaviablerouteofinfectionforpolymercoatedadenovirusretargetingintnfaactivatedhumanumbilicalveinendothelialcells AT stevensonm eselectinisaviablerouteofinfectionforpolymercoatedadenovirusretargetingintnfaactivatedhumanumbilicalveinendothelialcells AT subrv eselectinisaviablerouteofinfectionforpolymercoatedadenovirusretargetingintnfaactivatedhumanumbilicalveinendothelialcells AT seymourl eselectinisaviablerouteofinfectionforpolymercoatedadenovirusretargetingintnfaactivatedhumanumbilicalveinendothelialcells AT fisherk eselectinisaviablerouteofinfectionforpolymercoatedadenovirusretargetingintnfaactivatedhumanumbilicalveinendothelialcells |