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We take a look back at the key studies of adenovirus structure and biophysical properties, which revealed the mechanisms of adenovirus association with antibody, cell receptor, and immune molecules that regulate infection. In addition, we discuss the critical contribution of studies of adenovirus gene expression to elucidation of fundamental reactions in pre\u2010<jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> processing and its regulation. Other pioneering studies furnished the first examples of protein\u2010primed initiation of <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> synthesis and viral small <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s. As a nonenveloped virus, adenoviruses have furnished insights into the modes of virus attachment, entry, and penetration of host cells, and we discuss the diversity of cell receptors that support these processes, as well as membrane penetration. As a result of these extensive studies, adenovirus vectors were among the first to be developed for therapeutic applications. We highlight some of the early (unsuccessful) trials and the lessons learned from them.<\/jats:p>","DOI":"10.1002\/1873-3468.13700","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T12:49:22Z","timestamp":1574945362000},"page":"3395-3418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Lessons learned from adenovirus (1970\u20132019)"],"prefix":"10.1002","volume":"593","author":[{"given":"Glen","family":"Nemerow","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbial Science The Scripps Research Institute La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Flint","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Princeton University NJ 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