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Redirecting adenovirus to pulmonary endothelium by cationic liposomes

Gene Therapy volume 9, pages 176–182 (2002)Cite this article

Abstract

Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver gene transfer, have proven to be limited for pulmonary gene transfer with respect to efficiency, in part because of difficulty in assuring significant residence time in the lung and/or paucity of receptors for adenovirus on the endothelium. A recent study has shown that the use of a bispecific antibody to endothelial cells and Ad vectors efficiently redirects Ad vectors to pulmonary endothelium and improves gene expression in the lung. In this study, we report that pulmonary gene transfer by Ad vectors can also be improved significantly via the use of cationic liposomes. Preinjection of cationic liposomes followed by adenovirus led to a significant increase in the level of gene expression in the lung. The improvement in pulmonary gene transfer was associated with a decrease in the level of gene expression in the liver. Gene expression in the lung lasted for up to 2 weeks. This protocol, together with genetic modification of adenovirus, may prove to be useful for pulmonary gene transfer for the treatment of pulmonary diseases. This method may also be extended to pulmonary gene transfer using other types of viral vectors via vascular route.

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References

  1. Benihoud K., Yeh P., Perricaudet M. . Adenovirus vectors for gene delivery Curr Opin Biotechnol 1999 10: 440 440

    Article  CAS  PubMed  Google Scholar 

  2. Connelly S. . Adenoviral vectors for liver-directed gene therapy Curr Opin Mol Ther 1999 1: 565 565

    CAS  PubMed  Google Scholar 

  3. Krasnykh V.N., Douglas J.T., van Beusechem V.W. . Genetic targeting of adenoviral vectors Mol Ther 2000 1: 391 391

    Article  CAS  PubMed  Google Scholar 

  4. Krasnykh V. et al. Genetic targeting of an adenovirus vector via replacement of the fiber protein with the phage T4 fibritin J Virol 2001 75: 4176 4176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Shayakhmetov D.M., Papayannopoulou T., Stamatoyannopoulos G., Lieber A. . Efficient gene transfer into human CD34(+) cells by a retargeted adenovirus vector J Virol 2000 74: 2567 2567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wickham T.J. et al. Targeted adenovirus gene transfer to endothelial and smooth muscle cells by using bispecific antibodies J Virol 1996 70: 6831 6831

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Douglas J.T. et al. Targeted gene delivery by tropism-modified adenoviral vectors Nat Biotechnol 1996 14: 1548 1548

    Article  Google Scholar 

  8. Reynolds P.N. et al. A targetable injectable adenoviral vector for selective gene delivery to pulmonary endothelium in vivo Mol Ther 2000 2: 562 562

    Article  CAS  PubMed  Google Scholar 

  9. Trepel M., Grifman M., Weitzman M.D., Pasqualini R. . Molecular adaptors for vascular-targeted adenoviral gene delivery Hum Gene Ther 2000 11: 1971 1971

    Article  CAS  PubMed  Google Scholar 

  10. Tan Y. et al. Sequential injection of cationic liposome and plasmid DNA effectively transfects the lung with minimal inflammatory toxicity Mol Ther 2001 3: 673 673

    Article  CAS  PubMed  Google Scholar 

  11. Hodgson C.P., Solaiman F. . Virosomes: cationic liposomes enhance retroviral transduction Nat Biotechnol 1996 14: 339 339

    Article  CAS  PubMed  Google Scholar 

  12. Fasbender A. et al. Complexes of adenovirus with polycationic polymers and cationic lipids increase the efficiency of gene transfer in vitro and in vivo J Biol Chem 1997 272: 6479 6479

    Article  CAS  PubMed  Google Scholar 

  13. Arcasoy S.M. et al. Polycations increase the efficiency of adenovirus-mediated gene transfer to epithelial and endothelial cells in vitro Gene Therapy 1997 4: 32 32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Qiu C., DeYoung M.B., Finn A., Dichek D.A. . Cationic liposomes enhance adenovirus entry via a pathway independent of the fiber receptor and alpha(v)-integrins Hum Gene Ther 1998 9: 507 507

    Article  CAS  PubMed  Google Scholar 

  15. Clark P.R. et al. Polycations and cationic lipids enhance adenovirus transduction and transgene expression in tumor cells Cancer Gene Ther 1999 6: 437 437

    Article  CAS  PubMed  Google Scholar 

  16. Chillon M., Lee J.H., Fasbender A., Welsh M.J. . Adenovirus complexed with polyethylene glycol and cationic lipid is shielded from neutralizing antibodies in vitro Gene Therapy 1998 5: 995 995

    Article  CAS  PubMed  Google Scholar 

  17. Freimark B.D. et al. Cationic lipids enhance cytokine and cell influx levels in the lung following administration of plasmid: cationic lipid complexes J Immunol 1998 160: 4580 4580

    CAS  PubMed  Google Scholar 

  18. Li S. et al. Effect of immune response on gene transfer to the lung via systemic administration of cationic lipidic vectors Am J Physiol 1999 276: 796 796

    Article  Google Scholar 

  19. Yew N.S. et al. Contribution of plasmid DNA to inflammation in the lung after administration of cationic lipid:pDNA complexes Hum Gene Ther 1999 10: 223 223

    Article  CAS  PubMed  Google Scholar 

  20. Lanuti M. et al. Cationic lipid:bacterial DNA complexes elicit adaptive cellular immunity in murine intraperitoneal tumor models Cancer Res 2000 60: 2955 2955

    CAS  PubMed  Google Scholar 

  21. Song Y.K., Liu F., Liu D. . Enhanced gene expression in mouse lung by prolonging the retention time of intravenously injected plasmid DNA Gene Therapy 1998 5: 1531 1531

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by NIH grants HL63080 (to S Li), HL32154 and GM53789 (to B Pitt), and HL66949 and AR62225 (to P Robbins).

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Authors and Affiliations

  1. Center for Pharmacogenetics and Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA

    Z Ma & S Li

  2. Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Z Mi & PD Robbins

  3. Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    A Wilson & B Pitt

  4. Department of Cell Biology and Physiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    S Alber & S Watkins

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  1. Z Ma
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  6. S Watkins
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Ma, Z., Mi, Z., Wilson, A. et al. Redirecting adenovirus to pulmonary endothelium by cationic liposomes. Gene Ther 9, 176–182 (2002). https://doi.org/10.1038/sj.gt.3301636

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  • DOI: https://doi.org/10.1038/sj.gt.3301636

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