Skip to main content
SpringerLink
Log in

Doxycycline Sensitive Two-Promoter Integrator Based on the TET-ON 3G Transactivator

  • MOLECULAR CELL BIOLOGY
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

A synthetic genetic chain was created—a two-promoter integrator, the activity of the output signal of which is high only with the high activity of two promoters at the input of the chain. The integrator is shown to work by the example of cancer-specific promoters of the human survivin and telomerase genes that can be used for specific transcription of target genes in tumor cells. To create the integrator, we used the well-known TET-ON 3G transactivator, regulated by doxycycline.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

REFERENCES

  1. Li Y., Idamakanti N., Arroyo T., Thorne S., Reid T., Nichols S., VanRoey M., Colbern G., Nguyen N., Tam O., Working P., Yu D.C. 2005. Dual promoter-controlled oncolytic adenovirus CG5757 has strong tumor selectivity and significant antitumor efficacy in preclinical models. Clin. Cancer Res. 11 (24, Pt. 1), 8845‒8855.

    Article  CAS  Google Scholar 

  2. Ryan P.C., Jakubczak J.L., Stewart D.A., Hawkins L.K., Cheng C., Clarke L.M., Ganesh S., Hay C., Huang Y., Kaloss M., Marinov A., Phipps S.S., Reddy P.S., Shirley P.S., Skripchenko Y., et al. 2004. Antitumor efficacy and tumor-selective replication with a single intravenous injection of OAS403, an oncolytic adenovirus dependent on two prevalent alterations in human cancer. Cancer Gene Ther.11 (8), 555‒569.

    Article  CAS  Google Scholar 

  3. Liu Y., Zeng Y., Liu L., Zhuang C., Fu X., Huang W., Cai Z. 2014. Synthesizing AND gate genetic circuits based on CRISPR-Cas9 for identification of bladder cancer cells. Nat. Commun.5, 5393.

    Article  CAS  Google Scholar 

  4. Jerome V., Muller R. 1998. Tissue-specific, cell cycle-regulated chimeric transcription factors for the targeting of gene expression to tumor cells. Hum. Gene Ther.9 (18), 2653–2659.

    Article  CAS  Google Scholar 

  5. Jérôme V., Müller R. 2001. A synthetic leucine zipper-based dimerization system for combining multiple promoter specificities. Gene Ther.8 (9), 725‒729.

    Article  Google Scholar 

  6. Nissim L., Bar-Ziv R.H. 2010. A tunable dual-promoter integrator for targeting of cancer cells. Mol. Syst. Biol.6, 444.

    Article  Google Scholar 

  7. Wang H., Liu J., Yuet K.P., Hill A.J., Sternberg P.W. 2018. Split cGAL, an intersectional strategy using a split intein for refined spatiotemporal transgene control in Caenorhabditis elegans.Proc. Natl. Acad. Sci. U. S. A.115 (15), 3900‒3905.

    Article  CAS  Google Scholar 

  8. Scott E.K., Mason L., Arrenberg A.B., Ziv L., Gosse N.J., Xiao T., Chi N.C., Asakawa K., Kawakami K., Baier H. 2007. Targeting neural circuitry in zebrafish using GAL4 enhancer trapping. Nat. Methods.4 (4), 323–326.

    Article  CAS  Google Scholar 

  9. Shay J.W., Bacchetti S. 1997. A survey of telomerase activity in human cancer. Eur. J. Cancer.33 (5), 787‒791.

    Article  CAS  Google Scholar 

  10. Altieri D.C. 2008. Survivin, cancer networks and pathway-directed drug discovery. Nat. Rev. Cancer.8 (1), 61‒70.

    Article  CAS  Google Scholar 

  11. Zettler J., Schütz V., Mootz H.D. 2009. The naturally split Npu DnaE intein exhibits an extraordinarily high rate in the protein trans-splicing reaction. FEBS Lett.583 (5), 909‒914.

    Article  CAS  Google Scholar 

  12. Murofushi Y., Nagano S., Kamizono J., Takahashi T., Fujiwara H., Komiya S., Matsuishi T., Kosai K. 2006. Cell cycle-specific changes in hTERT promoter activity in normal and cancerous cells in adenoviral gene therapy: A promising implication of telomerase-dependent targeted cancer gene therapy. Int. J. Oncol.29 (3), 681‒688.

    CAS  PubMed  Google Scholar 

Download references

Funding

This study was financially supported by the Russian Foundation for Basic Research (project no. 18-04-00212 A). Work on the creation of genetic engineering structures was carried out with the support of the Russian Science Foundation, project no. 19-14-00112.

Author information

Authors and Affiliations

  1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997, Moscow, Russia

    Yu. M. Khodarovich, D. D. Rakhmaninova, A. M. Barishnikova & S. M. Deyev

Authors
  1. Yu. M. Khodarovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. D. Rakhmaninova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. M. Barishnikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. M. Deyev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yu. M. Khodarovich.

Ethics declarations

This article does not contain any research involving humans or animals as subjects of research.

Conflict of interest. The authors declare they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khodarovich, Y.M., Rakhmaninova, D.D., Barishnikova, A.M. et al. Doxycycline Sensitive Two-Promoter Integrator Based on the TET-ON 3G Transactivator. Mol Biol 54, 269–273 (2020). https://doi.org/10.1134/S0026893320020053

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893320020053

Keywords:

Search

Navigation