title: Use of a Novel Integrase-Deficient Lentivirus for Targeted Anti-Cancer Therapy With Survivin Promoter-Driven Diphtheria Toxin A.
abstract: As an immunotoxin, diphtheria toxin has been widely used in gene therapy and gene function assays for its roles in protein synthesis inhibition, and the aim of our study is to set up a nonintegrating lentiviral system for specific expression of diphtheria toxin A (DTA) used in cancer gene therapy.Here, we established a lentiviral system that could coordinately express fluorescent protein and DTA driven by the cytomegalovirus (CMV) promoter, which is convenient for us to precisely trace the expression of DTA and monitor the process of lentivirus packaging. To achieve safer cancer therapy, we replaced the CMV promoter with the Survivin promoter, a specific promoter that is dramatically activated in cancer tissues and cells, but not in normal tissues and cells, and that will impose greater therapeutic potential because a significant expression difference occurred between these 2 groups. Meanwhile, we obtained integrase-deficient lentivirus (IDLV) after packaging with the integrase mutant, which expresses defective integrase RRK262263264AAH, to minimize the side effects that derived from the insertional mutagenesis of the host genome.Our results suggest that the IDLV system that we generated possesses therapeutic potential in cancers in vitro and in vivo.
authors.affiliation: From the Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, Fujian, P.R. China (BL, AG, RZ, HM, MZ, XL, KL); Dong Fang Hospital, Xiamen University, Fuzhou, Fujian, P.R. China (BL, AG, QH, MZ, XL, KL); Institute for Laboratory Medicine, Fuzhou General Hospital, Second Military Medical University, Fuzhou, Fujian, P.R. China (HM); School of Pharmaceutical Science, Xiamen University, Xiamen, Fujian, P.R. China (HS); Agriculture and Animal Husbandry College, Tibet University, Nyingchi, P.R. China (HZ); and Fuzhou General Hospital Clinical Medical School, Fujian Medical University, Fuzhou, P.R. China (RZ, XL, KL).
authors.forename: Baoshun
authors.initials: B
authors.lastname: Lin
authors.forename: Anding
authors.initials: A
authors.lastname: Gao
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Ma
authors.forename: Haifeng
authors.initials: H
authors.lastname: Shen
authors.forename: Qiong
authors.initials: Q
authors.lastname: Hu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Zhao
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Lan
authors.forename: Kuancan
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D004167:Diphtheria Toxin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D019426:Integrases; D016086:Lentivirus; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000378:metabolism; D000077022:Survivin; D014162:Transfection / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: C107489:BIRC5 protein, human; D004167:Diphtheria Toxin; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin; D019426:Integrases