Characteristics of adenovirus-mediated tetracycline-controllable expression system - PubMed

Comparative Study

Characteristics of adenovirus-mediated tetracycline-controllable expression system

H Mizuguchi et al. Biochim Biophys Acta. 2001.

Abstract

The combination of recombinant adenovirus (Ad) vectors and the tetracycline-controllable expression system is clearly an advantage in gene therapy and gene transfer experiment. In this study, we examined the characteristics of Ad vectors containing the tet-off or tet-on system. The Ad vector containing the tet-off system showed tightly regulatable transgene expression even at low MOI (multiplicity of infection). In contrast, regulation of gene expression by the Ad vector containing the tet-on system was not tight at low MOI, while it showed moderate regulation at high MOI (MOI=100). The Ad vector-mediated tet-on system showed lower inducible and higher background (basal) luciferase production than that of the Ad vector-mediated tet-off system. Moreover, the former system required a concentration of doxycycline, a derivative of tetracycline, approx. 2-3 log orders higher than that of the latter system to switch the luciferase expression. A combination of the vector containing the tet-on system and the vector containing the tetracycline-controlled transcriptional silencer (tTS) gene reduced the background luciferase production and improved regulation. These results suggest that the Ad vector containing the tet-off system is considered to be functionally superior to the vector containing the tet-on system. Care should be taken regarding regulation (especially lower inducibility and higher background), which is decreased in the Ad vector-mediated tet-on system in comparison with the tet-off system. The Ad vector containing the tetracycline-controllable expression system should offer a powerful tool for gene therapy and gene transfer experimentation.

Similar articles

• Tight positive regulation of transgene expression by a single adenovirus vector containing the rtTA and tTS expression cassettes in separate genome regions.

  Mizuguchi H, Xu ZL, Sakurai F, Mayumi T, Hayakawa T. Mizuguchi H, et al. Hum Gene Ther. 2003 Sep 1;14(13):1265-77. doi: 10.1089/104303403767740803. Hum Gene Ther. 2003. PMID: 12952598

• The tet-off system is more effective than the tet-on system for regulating transgene expression in a single adenovirus vector.

  Mizuguchi H, Hayakawa T. Mizuguchi H, et al. J Gene Med. 2002 May-Jun;4(3):240-7. doi: 10.1002/jgm.261. J Gene Med. 2002. PMID: 12112641

• Efficient regulation of gene expression using self-contained fiber-modified adenovirus vectors containing the tet-off system.

  Mizuguchi H, Xu ZL, Sakurai F, Kawabata K, Yamaguchi T, Hayakawa T. Mizuguchi H, et al. J Control Release. 2005 Dec 10;110(1):202-11. doi: 10.1016/j.jconrel.2005.09.008. Epub 2005 Nov 8. J Control Release. 2005. PMID: 16278030

• Optimizing regulatable gene expression using adenoviral vectors.

  Lee YB, Glover CP, Cosgrave AS, Bienemann A, Uney JB. Lee YB, et al. Exp Physiol. 2005 Jan;90(1):33-7. doi: 10.1113/expphysiol.2004.028209. Epub 2004 Nov 12. Exp Physiol. 2005. PMID: 15542617 Review.

• Tet-On Systems For Doxycycline-inducible Gene Expression.

  Das AT, Tenenbaum L, Berkhout B. Das AT, et al. Curr Gene Ther. 2016;16(3):156-67. doi: 10.2174/1566523216666160524144041. Curr Gene Ther. 2016. PMID: 27216914 Free PMC article. Review.

Cited by

• Adenovirus vector-mediated assay system for hepatitis C virus replication.

  Yoshida T, Kondoh M, Ojima M, Mizuguchi H, Yamagishi Y, Sakamoto N, Yagi K. Yoshida T, et al. Nucleic Acids Res. 2011 May;39(10):e64. doi: 10.1093/nar/gkr047. Epub 2011 Feb 8. Nucleic Acids Res. 2011. PMID: 21306994 Free PMC article.

• Overexpression of miR-210 and its significance in ischemic tissue damage.

  Zaccagnini G, Maimone B, Fuschi P, Maselli D, Spinetti G, Gaetano C, Martelli F. Zaccagnini G, et al. Sci Rep. 2017 Aug 25;7(1):9563. doi: 10.1038/s41598-017-09763-4. Sci Rep. 2017. PMID: 28842599 Free PMC article.

• Establishment of a doxycycline-regulated cell line with inducible, doubly-stable expression of the wild-type p53 gene from p53-deleted hepatocellular carcinoma cells.

  Chi TY, Chen GG, Ho LK, Lai PB. Chi TY, et al. Cancer Cell Int. 2005 Aug 23;5:27. doi: 10.1186/1475-2867-5-27. Cancer Cell Int. 2005. PMID: 16117829 Free PMC article.

• Rescue and production of vaccine and therapeutic adenovirus vectors expressing inhibitory transgenes.

  Gall JG, Lizonova A, EttyReddy D, McVey D, Zuber M, Kovesdi I, Aughtman B, King CR, Brough DE. Gall JG, et al. Mol Biotechnol. 2007 Mar;35(3):263-73. doi: 10.1007/BF02686012. Mol Biotechnol. 2007. PMID: 17652790

• Generation of a PAX6 knockout glioblastoma cell line with changes in cell cycle distribution and sensitivity to oxidative stress.

  Hegge B, Sjøttem E, Mikkola I. Hegge B, et al. BMC Cancer. 2018 May 2;18(1):496. doi: 10.1186/s12885-018-4394-6. BMC Cancer. 2018. PMID: 29716531 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database