{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:54:41Z","timestamp":1783652081108,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["643130"],"award-info":[{"award-number":["643130"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oncolytic adenoviruses are in development as immunotherapeutic agents for solid tumors. Their efficacy is in part dependent on their ability to replicate in tumors. It is, however, difficult to obtain evidence for intratumoral oncolytic adenovirus replication if direct access to the tumor is not possible. Detection of systemic adenovirus DNA, which is sometimes used as a proxy, has limited value because it does not distinguish between the product of intratumoral replication and injected virus that did not replicate. Therefore, we investigated if detection of virus-associated RNA (VA RNA) by RT-qPCR on liquid biopsies could be used as an alternative. We found that VA RNA is expressed in adenovirus-infected cells in a replication-dependent manner and is secreted by these cells in association with extracellular vesicles. This allowed VA RNA detection in the peripheral blood of a preclinical in vivo model carrying adenovirus-injected human tumors and on liquid biopsies from a human clinical trial. Our results confirm that VA RNA detection in liquid biopsies can be used for minimally invasive assessment of oncolytic adenovirus replication in solid tumors in vivo.<\/jats:p>","DOI":"10.3390\/ijms25126551","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T08:52:10Z","timestamp":1718355130000},"page":"6551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Quantitative Virus-Associated RNA Detection to Monitor Oncolytic Adenovirus Replication"],"prefix":"10.3390","volume":"25","author":[{"given":"Tereza","family":"Brachtlova","sequence":"first","affiliation":[{"name":"Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"ORCA Therapeutics BV, 5223 DE \u2018s-Hertogenbosch, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Cancer Immunology, Amsterdam Institute for Infection and Immunity, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center Amsterdam, 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":"Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"Sluiter","sequence":"additional","affiliation":[{"name":"Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"von Meijenfeldt","sequence":"additional","affiliation":[{"name":"Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Witte","sequence":"additional","affiliation":[{"name":"Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5527-6827","authenticated-orcid":false,"given":"Sanne","family":"Massaar","sequence":"additional","affiliation":[{"name":"Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"van den Oever","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Erasmus MC, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"de Vrij","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Erasmus MC, 3015 GD Rotterdam, The Netherlands"},{"name":"ExoVectory BV, Biopartner 2 Building, 2333 CH Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor W.","family":"van Beusechem","sequence":"additional","affiliation":[{"name":"Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"ORCA Therapeutics BV, 5223 DE \u2018s-Hertogenbosch, The Netherlands"},{"name":"Cancer Biology and Immunology, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Cancer Immunology, Amsterdam Institute for Infection and Immunity, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mantwill, K., Klein, F.G., Wang, D., Hindupur, S.V., Ehrenfeld, M., Holm, P.S., and Nawroth, R. 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