{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:58:46Z","timestamp":1780333126463,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,8]],"date-time":"2021-05-08T00:00:00Z","timestamp":1620432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cancer Research UK","award":["C7838\/A25173"],"award-info":[{"award-number":["C7838\/A25173"]}]},{"name":"Cancer Research UK","award":["C52915\/A29104"],"award-info":[{"award-number":["C52915\/A29104"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>We previously developed a refined, tumor-selective adenovirus, Ad5NULL-A20, harboring tropism ablating mutations in each major capsid protein, to ablate all native means of infection. We incorporated a 20-mer peptide (A20) in the fiber knob for selective infection via \u03b1v\u03b26 integrin, a marker of aggressive epithelial cancers. Methods: To ascertain the selectivity of Ad5NULL-A20 for \u03b1v\u03b26-positive tumor cell lines of pancreatic and breast cancer origin, we performed reporter gene and cell viability assays. Biodistribution of viral vectors in mice harboring xenografts with low, medium, and high \u03b1v\u03b26 levels was quantified by qPCR for viral genomes 48 h post intravenous administration. Results: Ad5NULL-A20 vector transduced cells in an \u03b1v\u03b26-selective manner, whilst cell killing mediated by oncolytic Ad5NULL-A20 was \u03b1v\u03b26-selective. Biodistribution analysis following intravenous administration into mice bearing breast cancer xenografts demonstrated that Ad5NULL-A20 resulted in significantly reduced liver accumulation coupled with increased tumor accumulation compared to Ad5 in all three models, with tumor-to-liver ratios improved as a function of \u03b1v\u03b26 expression. Conclusions: Ad5NULL-A20-based virotherapies efficiently target \u03b1v\u03b26-integrin-positive tumors following intravenous administration, validating the potential of Ad5NULL-A20 for systemic applications, enabling tumor-selective overexpression of virally encoded therapeutic transgenes.<\/jats:p>","DOI":"10.3390\/v13050864","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T02:54:58Z","timestamp":1620615298000},"page":"864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Efficient Intravenous Tumor Targeting Using the \u03b1v\u03b26 Integrin-Selective Precision Virotherapy Ad5NULL-A20"],"prefix":"10.3390","volume":"13","author":[{"given":"James A.","family":"Davies","sequence":"first","affiliation":[{"name":"Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth","family":"Marlow","sequence":"additional","affiliation":[{"name":"Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanni K.","family":"Uusi-Kerttula","sequence":"additional","affiliation":[{"name":"Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Seaton","sequence":"additional","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Piggott","sequence":"additional","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luned M.","family":"Badder","sequence":"additional","affiliation":[{"name":"Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W. E.","family":"Clarkson","sequence":"additional","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Chester","sequence":"additional","affiliation":[{"name":"Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK"},{"name":"Velindre Cancer Centre, Cardiff CF14 2TL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9302-1761","authenticated-orcid":false,"given":"Alan L.","family":"Parker","sequence":"additional","affiliation":[{"name":"Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s40425-016-0158-5","article-title":"Into the clinic: Talimogene laherparepvec (T-VEC), a first-in-class intratumoral oncolytic viral therapy","volume":"4","author":"Rehman","year":"2016","journal-title":"J. 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