{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:24:48Z","timestamp":1787167488474,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:00:00Z","timestamp":1670284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003958","name":"Technology Foundation STW","doi-asserted-by":"publisher","award":["07710"],"award-info":[{"award-number":["07710"]}],"id":[{"id":"10.13039\/501100003958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oncolytic adenoviruses are promising new anticancer agents. To realize their full anticancer potential, they are being engineered to express therapeutic payloads. Tumor suppressor p53 function contributes to oncolytic adenovirus activity. Many cancer cells carry an intact TP53 gene but express p53 inhibitors that compromise p53 function. Therefore, we hypothesized that oncolytic adenoviruses could be made more effective by suppressing p53 inhibitors in selected cancer cells. To investigate this concept, we attenuated the expression of the established p53 inhibitor synoviolin (SYVN1) in A549 lung cancer cells by RNA interference. Silencing SYVN1 inhibited p53 degradation, thereby increasing p53 activity, and promoted adenovirus-induced A549 cell death. Based on these observations, we constructed a new oncolytic adenovirus that expresses a short hairpin RNA against SYVN1. This virus killed A549 cells more effectively in vitro and inhibited A549 xenograft tumor growth in vivo. Surprisingly, increased susceptibility to adenovirus-mediated cell killing by SYVN1 silencing was also observed in A549 TP53 knockout cells. Hence, while the mechanism of SYVN1-mediated inhibition of adenovirus replication is not fully understood, our results clearly show that RNA interference technology can be exploited to design more potent oncolytic adenoviruses.<\/jats:p>","DOI":"10.3390\/ijms232315430","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T01:47:46Z","timestamp":1670377666000},"page":"15430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of a Novel Oncolytic Adenovirus Silencing SYVN1"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4575-2874","authenticated-orcid":false,"given":"Christie","family":"Vermeulen","sequence":"first","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam, Medical Oncology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza","family":"Brachtlova","sequence":"additional","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam, Medical Oncology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"ORCA Therapeutics BV, Onderwijsboulevard 225, 5223 DE \u2018s Hertogenbosch, The Netherlands"},{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The Netherlands"},{"name":"Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki","family":"Tol","sequence":"additional","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam, Medical Oncology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3821-9927","authenticated-orcid":false,"given":"Ida H.","family":"van der Meulen-Muileman","sequence":"additional","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam, Medical Oncology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmina","family":"Hodzic","sequence":"additional","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam, Medical Oncology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri J.","family":"van de Vrugt","sequence":"additional","affiliation":[{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The Netherlands"},{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam, Human Genetics, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor W.","family":"van Beusechem","sequence":"additional","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam, Medical Oncology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"ORCA Therapeutics BV, Onderwijsboulevard 225, 5223 DE \u2018s Hertogenbosch, The Netherlands"},{"name":"Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The Netherlands"},{"name":"Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chaurasiya, S., Fong, Y., and Warner, S.G. 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