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Antiproliferative activity of G-quartet-containing oligonucleotides generated by a novel single-stranded DNA expression system

Cancer Gene Therapy volume 10, pages 867–869 (2003)Cite this article

Abstract

Recently, a novel single-stranded DNA (ssDNA) expression system that can generate intracellularly ssDNA or oligodeoxynucleotide (ODN) molecules has been developed. Previous studies showed that this ssDNA expression system is capable of generating DNA enzyme ODNs and triplex-forming oligodeoxynucleotides (TFOs) in cells. In this study, we constructed an ssDNA expression vector that can generate a G-quartet-containing ODNs, GRO29A, in cells. Similar to synthetic ODNs, vector-generated GRO29As were shown to have significant antiproliferative activities in a number of cancer cell lines. These results further demonstrate the potential application of ssDNA expression system in gene target validation and drug development.

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References

  1. Sen D, Gilbert W . Guanine quartet structure. Methods Enzymol. 1992;211:191–199.

    Article  CAS  Google Scholar 

  2. Han H, Hurley L . G-quadruplex DNA: a potential target for anti-cancer drug design. Trends Pharmacol Sci. 2000;21:136–142.

    Article  CAS  Google Scholar 

  3. Bates PJ, Kahlon JB, Thomas SD, et al. Antiproliferative activity of G-rich oligonucleotides correlates with protein binding. J Biol Chem. 1999;274:26369–26377.

    Article  CAS  Google Scholar 

  4. Xu X, Hamhouyia F, Thomas SD, et al. Inhibition of DNA replication and induction of S phase cell cycle arrest by G-rich oligonucleotides. J Biol Chem. 2001;276:43221–43230.

    Article  CAS  Google Scholar 

  5. Akhtar S, Hughes MD, Khan A, et al. The delivery of antisense therapeutics. Adv Drug Delivery Rev. 2000;44:3–21.

    Article  CAS  Google Scholar 

  6. Chen Y, Ji Y, Roxby R, Conrad C . In vivo expression of single-stranded DNA in mammalian cells with DNA enzyme sequences targeted to C-raf. Antisense Nucleic Acid Drug Dev. 2000;10:415–422.

    Article  CAS  Google Scholar 

  7. Chen Y, Ji Y, Conrad C . A novel system for the expression of single-stranded DNA in mammalian cells. Biotechniques. 2003;34:167–171.

    Article  CAS  Google Scholar 

  8. Datta HJ, Glazer PM . Intracellular generation of single-stranded DNA for chromosomal triplex formation and induced recombination. Nucleic Acid Res. 2001;29:5140–5147.

    Article  CAS  Google Scholar 

  9. Chen Y . A novel single-stranded DNA expression vector. Expert Opin Biol Ther. 2002;2:735–740.

    Article  CAS  Google Scholar 

  10. Tanase N, Goff SP . Domain structure of the Moloney murine leukemia virus reverse transcriptase: mutational analysis and separate expression of the DNA polymerase and RNase H activities. Proc Natl Acad Sci USA. 1988;85:1777–1781.

    Article  Google Scholar 

  11. Shinnick TM, Lerner RA, Sutcliffe JG . Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981;293:543–548.

    Article  CAS  Google Scholar 

  12. Marquet R, Isel C, Ehresmann C, Ehresmann B . tRNAs as primer of reverse transcriptase. Biochimie. 1995;77:113–124.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank L Casson for her technical support and M Skolnick for reviewing the manuscript.

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Authors and Affiliations

  1. CytoGenix, Inc., 9881 S. Wilcrest, Houston, 77099, Texas, USA

    Harilyn W McMicken & Yin Chen

  2. Department of Medicine, Human Molecular Biology Group, James Graham Brown Cancer Center, University of Louisville, Louisville, 40202, Kentucky, USA

    Paula J Bates

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  1. Harilyn W McMicken
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  2. Paula J Bates
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  3. Yin Chen
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Correspondence to Yin Chen.

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McMicken, H., Bates, P. & Chen, Y. Antiproliferative activity of G-quartet-containing oligonucleotides generated by a novel single-stranded DNA expression system. Cancer Gene Ther 10, 867–869 (2003). https://doi.org/10.1038/sj.cgt.7700652

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