title: A double-regulated oncolytic adenovirus with improved safety for adenocarcinoma therapy.
abstract: Safety and efficiency are equally important to be considered in developing oncolytic adenovirus. Previously, we have reported that ZD55, an oncolytic adenovirus with the deletion of E1B-55K gene, exhibited potent antitumor activity. In this study, to improve the safety of ZD55, we utilized MUC1 promoter to replace the native promoter of E1A on the basis of ZD55, and generated a double-regulated adenovirus, named MUD55. Our data demonstrated that the expression of early and late genes of MUD55 was both reduced in MUC1-negative cells, resulting in its stricter glandular-tumor selective progeny production. The cytopathic effect of MUD55 was about 10-fold lower than mono-regulated adenovirus ZD55 or Ad.MUC1 in normal cells and not obviously attenuated in glandular tumor cells. Moreover, MUD55 showed the least liver toxicity when administrated by intravenous injection in nude mice. These results indicate that MUD55 could be a promising candidate for the treatment of adenocarcinoma.
authors: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Na
authors: N
authors: Wei
authors: Jun Kai
authors: JK
authors: Fan
authors: Jin Fa
authors: JF
authors: Gu
authors: Ling Feng
authors: LF
authors: He
authors: Wen Hao
authors: WH
authors: Tang
authors: Xin
authors: X
authors: Cao
authors: Xin Yuan
authors: XY
authors: Liu
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003588:Cytopathogenic Effect, Viral; D015967:Gene Expression Regulation, Viral; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018396:Mucin-1 / Q000235:genetics; D050130:Oncolytic Virotherapy / Q000009:adverse effects; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1