title: Plasmid vectors harboring cellular promoters can induce prolonged gene expression in hematopoietic and mesenchymal progenitor cells.
abstract: Although prolonged transgene expression in progenitor cells might be desirable for modified cell therapy, the viral promoter-based expression vector tends to promote transgene expression only for a limited period. Here, we examined the ability of cellular promoters from elongation factor-1alpha (EF-1alpha) and ubiquitin C to drive gene expression in hematopoietic TF-1 and mesenchymal progenitor cells. We compared the expression levels and duration of a model gene, interleukin-2, generated by the cellular promoters to those by the cytomegalovirus (CMV) promoter. The EF-1alpha and ubiquitin C promoters drove prolonged gene expression in hematopoietic TF-1 and mesenchymal progenitor cells, whereas the CMV promoter did not. At day 7 after transfection in TF-1 cells, the mRNA expression levels of interleukin-2 driven by the EF-1alpha and ubiquitin C promoters were 118- and 56-fold higher, respectively, than those driven by the CMV promoter. Similarly, in mesenchymal progenitor cells, the expression levels of interleukin-2 driven by the EF-1alpha and ubiquitin C promoters were 98- and 20-fold higher, respectively, than that driven by the CMV promoter-encoding plasmid. Moreover, the ubiquitin C promoter directed higher levels of green fluorescence protein expression in mesenchymal progenitor cells than did the CMV promoter. These results indicate that the use of cellular promoters such as those for EF-1alpha and ubiquitin C might direct prolonged gene expression in hematopoietic and mesenchymal progenitor cells.
authors.affiliation: Research Institute of Basic Medical Science, College of Medicine, Pochon CHA University, Pochon, Kyonggi-do 487-800, Republic of Korea.
authors.forename: Hyang-Min
authors.initials: HM
authors.lastname: Byun
authors.forename: Dongchul
authors.initials: D
authors.lastname: Suh
authors.forename: Youngsin
authors.initials: Y
authors.lastname: Jeong
authors.forename: Hyung Seok
authors.initials: HS
authors.lastname: Wee
authors.forename: Jung Mogg
authors.initials: JM
authors.lastname: Kim
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Jung Jae
authors.initials: JJ
authors.lastname: Ko
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: Yong Bok
authors.initials: YB
authors.lastname: Lee
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D024861:Genetic Enhancement / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D020648:Peptide Elongation Factor 1 / Q000502:physiology*; D010957:Plasmids / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015202:Protein Engineering / Q000379:methods*; D025822:Ubiquitin C / Q000502:physiology*
chemical_list: D020648:Peptide Elongation Factor 1; D025822:Ubiquitin C