Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Communication
  • Published:

φc31 integrase induces chromosomal aberrations in primary human fibroblasts

Gene Therapy volume 13, pages 1188–1190 (2006)Cite this article

Abstract

φc31 integrase is investigated as a novel tool for nonviral gene therapy as the enzyme can direct site-specific integration into a host chromosome. In order to investigate effects of φc31 integrase expression in normal human cells, we have generated stably transfected primary human fibroblasts expressing the enzyme. All control cells were cytogenetically normal, but in cells expressing φc31 integrase, numerous chromosomal abnormalities including various translocations were found, suggesting that the enzyme itself acts as a mutagen.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Thorpe HM, Smith MC . In vitro site-specific integration of bacteriophage DNA catalyzed by a recombinase of the resolvase/invertase family. Proc Natl Acad Sci USA 1998; 95: 5505–5510.

    Article  CAS  Google Scholar 

  2. Thyagarajan B, Olivares EC, Hollis RP, Ginsburg DS, Calos MP . Site-specific genomic integration in mammalian cells mediated by phage phiC31 integrase. Mol Cell Biol 2001; 21: 3926–3934.

    Article  CAS  Google Scholar 

  3. Chalberg TW, Portlock JL, Olivares EC, Thyagarajan B, Kirby PJ, Hillman RT et al. Integration specificity of phage varphiC31 integrase in the human genome. J Mol Biol 2005; 357: 28–48.

    Article  Google Scholar 

  4. Ginsburg DS, Calos MP . Site-specific integration with phiC31 integrase for prolonged expression of therapeutic genes. Adv Genet 2005; 54: 179–187.

    Article  CAS  Google Scholar 

  5. Olivares EC, Hollis RP, Chalberg TW, Meuse L, Kay MA, Calos MP . Site-specific genomic integration produces therapeutic Factor IX levels in mice. Nat Biotechnol 2002; 20: 1124–1128.

    Article  CAS  Google Scholar 

  6. Ortiz-Urda S, Thyagarajan B, Keene DR, Lin Q, Fang M, Calos MP et al. Stable nonviral genetic correction of inherited human skin disease. Nat Med 2002; 8: 1166–1170.

    Article  CAS  Google Scholar 

  7. Ortiz-Urda S, Thyagarajan B, Keene DR, Lin Q, Calos MP, Khavari PA . PhiC31 integrase-mediated nonviral genetic correction of junctional epidermolysis bullosa. Hum Gene Ther 2003; 14: 923–928.

    Article  CAS  Google Scholar 

  8. Held PK, Olivares EC, Aguilar CP, Finegold M, Calos MP, Grompe M . In vivo correction of murine hereditary tyrosinemia type I by phiC31 integrase-mediated gene delivery. Mol Ther 2005; 11: 399–408.

    Article  CAS  Google Scholar 

  9. Ehrhardt A, Xu H, Huang Z, Engler JA, Kay MA . A direct comparison of two nonviral gene therapy vectors for somatic integration: in vivo evaluation of the bacteriophage integrase phiC31 and the Sleeping Beauty transposase. Mol Ther 2005; 11: 695–706.

    Article  CAS  Google Scholar 

  10. Mitelman F . ISCN: An International System for Human Cytogenetics Nomenclature. S Karger: Basel, Switzerland, 1995.

    Google Scholar 

  11. Loonstra A, Vooijs M, Beverloo HB, Allak BA, van Drunen E, Kanaar R et al. Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells. Proc Natl Acad Sci USA 2001; 98: 9209–9214.

    Article  CAS  Google Scholar 

  12. Belteki G, Gertsenstein M, Ow DW, Nagy A . Site-specific cassette exchange and germline transmission with mouse ES cells expressing phiC31 integrase. Nat Biotechnol 2003; 21: 321–324.

    Article  CAS  Google Scholar 

  13. Hollis RP, Stoll SM, Sclimenti CR, Lin J, Chen-Tsai Y, Calos MP . Phage integrases for the construction and manipulation of transgenic mammals. Reprod Biol Endocrinol 2003; 1: 79.

    Article  Google Scholar 

  14. Groth AC, Fish M, Nusse R, Calos MP . Construction of transgenic Drosophila by using the site-specific integrase from phage phiC31. Genetics 2004; 166: 1775–1782.

    Article  CAS  Google Scholar 

  15. McKinlay Gardner RJ, Sutherland GR . Chromosome Abnormalities and Genetic Counseling. Oxford University Press: Oxford, 2004, pp 142–162.

    Google Scholar 

Download references

Acknowledgements

Dr Michele Calos, Stanford, is thanked for the generous gift of the plasmids pCMVInt and pTA-attB. This work was supported by the The Danish Medical Research Council, The Velux Foundation and the Novo Nordisk Foundation.

Author information

Authors and Affiliations

  1. Kennedy Institute-National Eye Clinic, Glostrup, Denmark

    J Liu, I Jeppesen, K Nielsen & T G Jensen

Authors
  1. J Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I Jeppesen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T G Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T G Jensen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, J., Jeppesen, I., Nielsen, K. et al. φc31 integrase induces chromosomal aberrations in primary human fibroblasts. Gene Ther 13, 1188–1190 (2006). https://doi.org/10.1038/sj.gt.3302789

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3302789

Keywords

This article is cited by

Search

Advanced search

Quick links