Employment of microarray analysis to characterize biologic differences associated with tropism-modified adenoviral vectors: utilization of non-native cellular entry pathways.
In this study, we have applied high-density oligonucleotide microarray technology to characterize biologic changes associated with adenoviral vector-mediated target cell infection. We infected a human melanoma cell line, M21, with the tropism-modified vectors, Ad5lucRGD and Ad5/3luc1. In addition, we infected the M21 cell line with the Ad5luc1, a vector which primarily exploits the coxsackie and adenovirus receptor, as its primary native receptor. We found significant changes in gene expression of 5492 genes induced by Ad5luc1 infection, 2439 genes induced by Ad5/3luc1 infection, and 1251 genes induced by Ad5lucRGD infection, compared to uninfected cells. Among these changes in gene expression, 783 changes were common to Ad5/3luc1 and Ad5luc1 infections, 266 were common to Ad5lucRGD and Ad5luc1 infections, and 185 changes in gene expression were common to Ad5/3luc1 and Ad5lucRGD infections. Interestingly, 89 changes in gene expression were common to all the three groups, suggesting a commonly affected pathway. This analysis represents a unique application of microarray to study vector-related issues. Furthermore, these studies demonstrate the utility of microarray for characterizing the biologic sequelae of host-vector interaction.
Volk
Andrea L
AL
Division of Human Gene Therapy and The Gene Therapy Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Rivera
Angel A
AA
Page
Grier P
GP
Salazar-Gonzalez
Jesus F
JF
Nettelbeck
Dirk M
DM
Matthews
Qiana L
QL
Curiel
David T
DT
D000256:Adenoviridae / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008545:Melanoma / Q000235:genetics / Q000628:therapy*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000628:therapy*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D008156:Luciferases