1.Gene expression of tumor cells both in vitro and in vivo enhanced by integrin-targeting adenovirus vector.
Jian-qing GAO ; Hai-liang CHEN ; Shinsaku NAKAGAWA ; Hiroyuki MIZUGUCHI ; Wen-quan LIANG
Acta Pharmaceutica Sinica 2006;41(11):1116-1120
AIMTo construct an efficient recombinant viral vector for gene therapy.
METHODSFirst-generation adenovirus (Ad) vector was modified with the RGD peptide inserted into the fiber. Both in vitro and in vivo experiments of gene expression in different tumor cells with conventional and recombinant vectors were conducted. RT-PCR was used for detecting the expression of coxackievirus and adenovirus receptor and integrin at the surface of Meth-A cells.
RESULTSFiber-mutant adenovirus vector showed a notably enhanced gene expression in A2058, B16BL6, OV-HM, and Meth-A tumor cells compared with that of conventional ones. In vivo study carried out using Meth-A tumor-bearing mice also demonstrated that the intra-tumoral injection of recombinant adenovirus induced strong gene expression in these CAR-deficient tumor cells.
CONCLUSIONThe recombinant vector can be a promising one for effective cancer gene therapy.
Adenoviridae ; genetics ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Cell Line, Tumor ; Enterovirus ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Therapy ; methods ; Genetic Vectors ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Integrins ; genetics ; metabolism ; Luciferases ; genetics ; metabolism ; Mice ; Mice, Inbred BALB C ; Microscopy, Fluorescence ; Mutation ; Neoplasm Transplantation ; Neoplasms, Experimental ; genetics ; pathology ; therapy ; Oligopeptides ; genetics ; Receptors, Virus ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection