{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:30:25Z","timestamp":1788975025931,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004807","name":"California Department of Fish and Game","doi-asserted-by":"publisher","award":["EH 192\/5\u20101 (AE)"],"award-info":[{"award-number":["EH 192\/5\u20101 (AE)"]}],"id":[{"id":"10.13039\/100004807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Adenoviral vectors are among the most frequently used vectors for gene therapy and cancer treatment. Most vectors are derived from human adenovirus (Ad) serotype 5 despite limited applicability caused by pre\u2010existing immunity and unfavorable liver tropism, whereas the other more than 100 known human serotypes remain largely unused. Here, we screened a library of human Ad types and identified Ad4 as a promising candidate vector.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Reporter\u2010gene\u2010expressing viruses representative of the natural human Ad diversity were used to transduce an array of muscle cell lines and two\u2010 or three\u2010dimensional tumor cultures. The time\u2010course of transgene expression was monitored by fluorescence or luminescence measurements. To generate replication\u2010deficient Ad4 vector genomes, successive homologous recombination was applied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ad4, 17 and 50 transduced human cardiomyocytes more efficiently than Ad5, whereas Ad37 was found to be superior in rhabdomyocytes. Despite its moderate transduction efficiency, Ad4 showed efficient and long\u2010lasting gene expression in papillomavirus (HPV) positive tumor organoids. Therefore, we aimed to harness the potential of Ad4 for improved muscle transduction or oncolytic virotherapy of HPV\u2010positive tumors. We deleted the E1 and E3 transcription units to produce first generation Ad vectors for gene therapy. The E1\u2010 and E1\/E3\u2010deleted vectors were replication\u2010competent in HEK293 cells stably expressing E1 but not in the other cell lines tested. Furthermore, we show that the Ad5 E1 transcription unit can complement the replication of E1\u2010deleted Ad4 vectors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our Ad4\u2010based gene therapy vector platform contributes to the development of improved Ad vectors based on non\u2010canonical serotypes for a broad range of applications.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3576","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T01:00:32Z","timestamp":1692061232000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Development of oncolytic and gene therapy vectors based on adenovirus serotype 4 as an alternative to adenovirus serotype 5"],"prefix":"10.1002","volume":"26","author":[{"given":"Erwan","family":"Sallard","sequence":"first","affiliation":[{"name":"Virology and Microbiology, Center for Biomedical Education and Research (ZBAF), 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