{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:30:36Z","timestamp":1771597836825,"version":"3.50.1"},"reference-count":18,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T00:00:00Z","timestamp":1576540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008425","name":"Conseller\u00eda de Cultura, Educaci\u00f3n e Ordenaci\u00f3n Universitaria, Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431C 2018\/28"],"award-info":[{"award-number":["ED431C 2018\/28"]}],"id":[{"id":"10.13039\/501100008425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017266","name":"Gobierno de Navarra","doi-asserted-by":"publisher","award":["Ref.: 0011-1383-2018-000011 PT038 and 0011-1383-2019-000006 PT013 (XANTOGEN)."],"award-info":[{"award-number":["Ref.: 0011-1383-2018-000011 PT038 and 0011-1383-2019-000006 PT013 (XANTOGEN)."]}],"id":[{"id":"10.13039\/501100017266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Viral vector use is wide-spread in the field of gene therapy, with new clinical trials starting every year for different human pathologies and a growing number of agents being approved by regulatory agencies. However, preclinical testing is long and expensive, especially during the early stages of development. Nowadays, the model organism par excellence is the mouse (Mus musculus), and there are few investigations in which alternative models are used. Here, we assess the possibility of using zebrafish (Danio rerio) as an in vivo model for adenoviral vectors. We describe how E1\/E3-deleted adenoviral vectors achieve efficient transduction when they are administered to zebrafish embryos via intracranial injection. In addition, helper-dependent (high-capacity) adenoviral vectors allow sustained transgene expression in this organism. Taking into account the wide repertoire of genetically modified zebrafish lines, the ethical aspects, and the affordability of this model, we conclude that zebrafish could be an efficient alternative for the early-stage preclinical evaluation of adenoviral vectors.<\/jats:p>","DOI":"10.3390\/genes10121053","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T05:25:53Z","timestamp":1576819553000},"page":"1053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Danio Rerio as Model Organism for Adenoviral Vector Evaluation"],"prefix":"10.3390","volume":"10","author":[{"given":"Paola","family":"Gul\u00edas","sequence":"first","affiliation":[{"name":"Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8365-7125","authenticated-orcid":false,"given":"Jorge","family":"Guerra-Varela","sequence":"additional","affiliation":[{"name":"Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Gonzalez-Aparicio","sequence":"additional","affiliation":[{"name":"Gene Therapy and Regulation of Gene Expression Program, CIMA, FIMA, University of Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, IDISNA, Pamplona, 31009 Navarra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Ricobaraza","sequence":"additional","affiliation":[{"name":"Gene Therapy and Regulation of Gene Expression Program, CIMA, FIMA, University of Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, IDISNA, Pamplona, 31009 Navarra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Africa","family":"Vales","sequence":"additional","affiliation":[{"name":"Gene Therapy and Regulation of Gene Expression Program, CIMA, FIMA, University of Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, IDISNA, Pamplona, 31009 Navarra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1600-4562","authenticated-orcid":false,"given":"Gloria","family":"Gonzalez-Aseguinolaza","sequence":"additional","affiliation":[{"name":"Gene Therapy and Regulation of Gene Expression Program, CIMA, FIMA, University of Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, IDISNA, Pamplona, 31009 Navarra, Spain"},{"name":"Vivet Therapeutics SAS, 75008 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rub\u00e9n","family":"Hernandez-Alcoceba","sequence":"additional","affiliation":[{"name":"Gene Therapy and Regulation of Gene Expression Program, CIMA, FIMA, University of Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, IDISNA, Pamplona, 31009 Navarra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7927-5303","authenticated-orcid":false,"given":"Laura","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, L., Li, F., Dang, L., Liang, C., He, B., and Liu, J. (2016). In vivo delivery systems for therapeutic genome editing. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050626"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lundstrom, K. (2018). Viral vectors in gene therapy. Diseases, 6.","DOI":"10.3390\/diseases6020042"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1089\/hum.2013.2527","article-title":"Adenovirus: The first effective in vivo gene delivery vector","volume":"25","author":"Crustal","year":"2014","journal-title":"Hum. Gene. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/mt.2011.243","article-title":"Immune-mediated loss of transgene expression from virally transduced brain cells is irreversible, mediated by IFN\u03b3, perforin, and TNF\u03b1, and due to the elimination of transduced cells","volume":"20","author":"Zirger","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"370","DOI":"10.2174\/156652321305131212125338","article-title":"Helper dependent adenovirus vectors: Progress and future prospects","volume":"13","author":"Cots","year":"2013","journal-title":"Curr. Gene Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1038\/sj.mt.6300305","article-title":"One-year expression from high-capacity adenoviral vectors in the brains of animals with pre-existing anti-adenoviral immunity: Clinical implications","volume":"15","author":"Barcia","year":"2007","journal-title":"Mol. Gene Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1089\/hum.2013.071","article-title":"Transgene expression up to 7 years in nonhuman primates following hepatic transduction with helper-dependent adenoviral vectors","volume":"24","author":"Ng","year":"2013","journal-title":"Hum. Gene Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/ilar.53.2.161","article-title":"Zebrafish breeding in the laboratory environment","volume":"53","author":"Nasiadka","year":"2012","journal-title":"ILAR J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0959-437X(00)00074-5","article-title":"Zebrafish: A model system for the study of human diseases","volume":"10","author":"Dooley","year":"2000","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.tcb.2013.09.009","article-title":"Of fish and men: Using zebrafish to fight human diseases","volume":"23","author":"Albain","year":"2013","journal-title":"Trends. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature12111","article-title":"The zebrafish reference genome sequence and its relationship to the human genome","volume":"496","author":"Howe","year":"2013","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12236","DOI":"10.1128\/JVI.01205-06","article-title":"Effect of adenovirus-mediated RNA interference on endogenous microRNAs in a mouse model of multidrug resistance protein 2 gene silencing","volume":"80","author":"Narvaiza","year":"2006","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/gt.2011.58","article-title":"Self-inactivating helper virus for the production of high-capacity adenoviral vectors","volume":"18","author":"Mauleon","year":"2011","journal-title":"Gene Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12302-014-0032-3","article-title":"Microinjection into zebrafish embryos (Danio rerio)\u2014A useful tool in aquatic toxicity testing?","volume":"26","author":"Schubert","year":"2014","journal-title":"Environ. Sci. Eur."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/1074-7613(94)90074-4","article-title":"MHC class I-cestricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses","volume":"1","author":"Yang","year":"1994","journal-title":"Immunity"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0145-305X(03)00103-4","article-title":"Development and maturation of the immune system in zebrafish, Danio rerio: A gene expression profiling, in situ hybridization and immunological study","volume":"28","author":"Lam","year":"2004","journal-title":"Dev. Comp. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.trsl.2015.12.007","article-title":"Novel immunologic tolerance of human cancer cell xenotransplants in zebrafish","volume":"170","author":"Zhang","year":"2016","journal-title":"Transl. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1002\/dvdy.22113","article-title":"Normal table of post-embryonic zebrafish development: Staging by externally visible anatomy of the living fish","volume":"238","author":"Parichy","year":"2009","journal-title":"Dev. 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