{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T02:17:48Z","timestamp":1778897868371,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,22]],"date-time":"2023-01-22T00:00:00Z","timestamp":1674345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["108307"],"award-info":[{"award-number":["108307"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["Physician-Scientist fellowship"],"award-info":[{"award-number":["Physician-Scientist fellowship"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["Mildred-Scheel fellowship"],"award-info":[{"award-number":["Mildred-Scheel fellowship"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Faculty, Heidelberg University","award":["108307"],"award-info":[{"award-number":["108307"]}]},{"name":"Medical Faculty, Heidelberg University","award":["Physician-Scientist fellowship"],"award-info":[{"award-number":["Physician-Scientist fellowship"]}]},{"name":"Medical Faculty, Heidelberg University","award":["Mildred-Scheel fellowship"],"award-info":[{"award-number":["Mildred-Scheel fellowship"]}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["108307"],"award-info":[{"award-number":["108307"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["Physician-Scientist fellowship"],"award-info":[{"award-number":["Physician-Scientist fellowship"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["Mildred-Scheel fellowship"],"award-info":[{"award-number":["Mildred-Scheel fellowship"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Virotherapy is a promising, novel form of cancer immunotherapy currently being investigated in pre-clinical and clinical settings. While generally well-tolerated, the anti-tumor potency of oncolytic virus-based monotherapies needs to be improved further. One of the major factors limiting the replication efficiency of oncolytic viruses are the antiviral defense pathways activated by tumor cells. In this study, we have designed and validated a universal expression cassette for artificial microRNAs that can now be adapted to suppress genes of interest, including potential resistance factors. Transcripts are encoded as a primary microRNA for processing via the predominantly nuclear RNase III Drosha. We have engineered an oncolytic measles virus encoding this universal expression cassette for artificial microRNAs. Virally encoded microRNA was expressed in the range of endogenous microRNA transcripts and successfully mediated target protein suppression. However, absolute expression levels of mature microRNAs were limited when delivered by an oncolytic measles virus. We demonstrate that measles virus, in contrast to other cytosolic viruses, does not induce translocation of Drosha from the nucleus into the cytoplasm, potentially resulting in a limited processing efficiency of virus-derived, cytosolically delivered artificial microRNAs. To our knowledge, this is the first report demonstrating functional expression of microRNA from oncolytic measles viruses potentially enabling future targeted knockdown, for instance of antiviral factors specifically in tumor cells.<\/jats:p>","DOI":"10.3390\/v15020308","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T03:26:41Z","timestamp":1674444401000},"page":"308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Oncolytic Measles Virus Encoding MicroRNA for Targeted RNA Interference"],"prefix":"10.3390","volume":"15","author":[{"given":"Sophie C.","family":"Anker","sequence":"first","affiliation":[{"name":"Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"},{"name":"Department of Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Im Neuenheimer Feld 671, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie G.","family":"Szczeponik","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"},{"name":"Medical School, Heidelberg University, Im Neuenheimer Feld 672, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Dessila","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Dittus","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"},{"name":"Faculty of Biosciences, Heidelberg University, Im Neuenheimer Feld 234, 69120 Heidelberg, Germany"},{"name":"Department of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6032-8786","authenticated-orcid":false,"given":"Christine E.","family":"Engeland","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"},{"name":"Department of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany"},{"name":"Center for Biomedical Research and Education (ZBAF), Institute of Virology and Microbiology, Faculty of Health, School of Medicine, Witten\/Herdecke University, Stockumer Stra\u00dfe 10, 58453 Witten, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Ungerechts","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"},{"name":"Department of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany"},{"name":"Cancer Therapeutics Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8773-1169","authenticated-orcid":false,"given":"Mathias F.","family":"Leber","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"},{"name":"Department of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/sj.mt.6300108","article-title":"History of oncolytic viruses: Genesis to genetic engineering","volume":"15","author":"Kelly","year":"2007","journal-title":"Mol. 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