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Adenovirus Serotype 5 Variants Defective in Early Genes: Selective Replication in p53-Deficient Human Tumor Cells
Site-directed mutagenesis was used to construct human adenovirus serotype 5 (Ad5) variants defective in E1A or E1B. Mutant Adel3 with deletion from E1A was markedly attenuated in permissive cell cultures regardless of the p53 status, and replicated efficiently only in cells of the complementing 293...
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Published in: | Molecular biology (New York) 2003-09, Vol.37 (5), p.739-745 |
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creator | Kachko, A V Svyatchenko, V A Ternovoi, V A Kiselev, N N Sorokin, A V Kiselev, S L Georgiev, G P Netesov, S V |
description | Site-directed mutagenesis was used to construct human adenovirus serotype 5 (Ad5) variants defective in E1A or E1B. Mutant Adel3 with deletion from E1A was markedly attenuated in permissive cell cultures regardless of the p53 status, and replicated efficiently only in cells of the complementing 293 line. Mutant Adel2 with deletion from E1B55K infected the 293 line cells and p53-deficient human tumor cells (A431, SW480, HEp2) with efficiencies similar to those of Ad5, whereas its replication in normal p53-positive cells was substantially limited. Thus, Adel2 proved to be capable of selective infection and lysis of p53-deficient human tumor cells in vitro. On intratumor injection, Adel2 dramatically suppressed the growth of human epidermoid carcinoma (A431) in nude mice. Adel2 is thus a promising model for designing therapeutic agents against p53-deficient human tumors.[PUBLICATION ABSTRACT] |
doi_str_mv | 10.1023/A:1026093112245 |
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Mutant Adel3 with deletion from E1A was markedly attenuated in permissive cell cultures regardless of the p53 status, and replicated efficiently only in cells of the complementing 293 line. Mutant Adel2 with deletion from E1B55K infected the 293 line cells and p53-deficient human tumor cells (A431, SW480, HEp2) with efficiencies similar to those of Ad5, whereas its replication in normal p53-positive cells was substantially limited. Thus, Adel2 proved to be capable of selective infection and lysis of p53-deficient human tumor cells in vitro. On intratumor injection, Adel2 dramatically suppressed the growth of human epidermoid carcinoma (A431) in nude mice. Adel2 is thus a promising model for designing therapeutic agents against p53-deficient human tumors.[PUBLICATION ABSTRACT]</description><identifier>ISSN: 0026-8933</identifier><identifier>EISSN: 1608-3245</identifier><identifier>DOI: 10.1023/A:1026093112245</identifier><language>eng</language><publisher>New York: Springer Nature B.V</publisher><subject>Adenovirus ; Adenoviruses ; Animal models ; Carcinoma ; Cell culture ; Human adenovirus ; Infection ; p53 protein ; Permissive cells ; Replication ; Rodents ; Serotypes ; Site-directed mutagenesis ; Tumor cells ; Tumors</subject><ispartof>Molecular biology (New York), 2003-09, Vol.37 (5), p.739-745</ispartof><rights>MAIK "Nauka/Interperiodica" 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Kachko, A V</creatorcontrib><creatorcontrib>Svyatchenko, V A</creatorcontrib><creatorcontrib>Ternovoi, V A</creatorcontrib><creatorcontrib>Kiselev, N N</creatorcontrib><creatorcontrib>Sorokin, A V</creatorcontrib><creatorcontrib>Kiselev, S L</creatorcontrib><creatorcontrib>Georgiev, G P</creatorcontrib><creatorcontrib>Netesov, S V</creatorcontrib><title>Adenovirus Serotype 5 Variants Defective in Early Genes: Selective Replication in p53-Deficient Human Tumor Cells</title><title>Molecular biology (New York)</title><description>Site-directed mutagenesis was used to construct human adenovirus serotype 5 (Ad5) variants defective in E1A or E1B. 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subjects | Adenovirus Adenoviruses Animal models Carcinoma Cell culture Human adenovirus Infection p53 protein Permissive cells Replication Rodents Serotypes Site-directed mutagenesis Tumor cells Tumors |
title | Adenovirus Serotype 5 Variants Defective in Early Genes: Selective Replication in p53-Deficient Human Tumor Cells |
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