{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:41:01Z","timestamp":1780393261736,"version":"3.54.1"},"reference-count":209,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["15\/26580-9"],"award-info":[{"award-number":["15\/26580-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Recent preclinical and clinical studies have used viral vectors in gene therapy research, especially nonreplicating adenovirus encoding strategic therapeutic genes for cancer treatment. Adenoviruses were the first DNA viruses to go into therapeutic development, mainly due to well-known biological features: stability in vivo, ease of manufacture, and efficient gene delivery to dividing and nondividing cells. However, there are some limitations for gene therapy using adenoviral vectors, such as nonspecific transduction of normal cells and liver sequestration and neutralization by antibodies, especially when administered systemically. On the other hand, adenoviral vectors are amenable to strategies for the modification of their biological structures, including genetic manipulation of viral proteins, pseudotyping, and conjugation with polymers or biological membranes. Such modifications provide greater specificity to the target cell and better safety in systemic administration; thus, a reduction of antiviral host responses would favor the use of adenoviral vectors in cancer immunotherapy. In this review, we describe the structural and molecular features of nonreplicating adenoviral vectors, the current limitations to their use, and strategies to modify adenoviral tropism, highlighting the approaches that may allow for the systemic administration of gene therapy.<\/jats:p>","DOI":"10.3390\/cancers13081863","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T04:21:08Z","timestamp":1618374068000},"page":"1863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Nonreplicating Adenoviral Vectors: Improving Tropism and Delivery of Cancer Gene Therapy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4735-6971","authenticated-orcid":false,"given":"Nayara Gusm\u00e3o","family":"Tessarollo","sequence":"first","affiliation":[{"name":"Viral Vector Laboratory, Center for Translational Investigation in Oncology, Cancer Institute of S\u00e3o Paulo\/LIM24, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0025-7167","authenticated-orcid":false,"given":"Ana Carolina M.","family":"Domingues","sequence":"additional","affiliation":[{"name":"Viral Vector Laboratory, Center for Translational Investigation in Oncology, Cancer Institute of S\u00e3o Paulo\/LIM24, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7261-451X","authenticated-orcid":false,"given":"Fernanda","family":"Antunes","sequence":"additional","affiliation":[{"name":"Viral Vector Laboratory, Center for Translational Investigation in Oncology, Cancer Institute of S\u00e3o Paulo\/LIM24, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Carlos dos Santos da","family":"Luz","sequence":"additional","affiliation":[{"name":"Viral Vector Laboratory, Center for Translational Investigation in Oncology, Cancer Institute of S\u00e3o Paulo\/LIM24, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otavio Augusto","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Viral Vector Laboratory, Center for Translational Investigation in Oncology, Cancer Institute of S\u00e3o Paulo\/LIM24, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto Luiz Dutra","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"Viral Vector Laboratory, Center for Translational Investigation in Oncology, Cancer Institute of S\u00e3o Paulo\/LIM24, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4113-9450","authenticated-orcid":false,"given":"Bryan E.","family":"Strauss","sequence":"additional","affiliation":[{"name":"Viral Vector Laboratory, Center for Translational Investigation in Oncology, Cancer Institute of S\u00e3o Paulo\/LIM24, University of S\u00e3o Paulo School of Medicine, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e3015","DOI":"10.1002\/jgm.3015","article-title":"Gene therapy clinical trials worldwide to 2017: An update","volume":"20","author":"Ginn","year":"2018","journal-title":"J. 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