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A simple, lanthanide-based method to enhance the transduction efficiency of adenovirus vectors

Gene Therapy volume 15, pages 357–363 (2008)Cite this article

Abstract

Based upon the powerful bridging and charge-masking properties of lanthanide cations (Ln3+), we have investigated their use to improve the transduction efficiency of adenovirus vectors. Using a luciferase marker gene, it was possible to increase transgene expression by the murine mesenchymal stem cell line C3H10T½ by up to four log orders when using very low multiplicities of infection in conjunction with Ln3+; La3+ was superior to Gd3+, Y3+ and Lu3+ in this regard. All Ln3+ were more effective than Ca2+. Flow cytometry, using a green fluorescent protein marker gene, confirmed that La3+ increased both the percentage of transduced cells and the level of transgene expression per cell. Transduction of primary cultures of a variety of different mesenchymal cells from human, rabbit, bovine and rat sources, as well as gene transfer to synovium and muscle in vivo, was also greatly enhanced. Our findings suggest that this lanthanide-based method holds much promise for expediting both experimental and clinical applications of gene transfer with adenoviral vectors.

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References

  1. Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab 2003; 80: 148–158.

    Article  CAS  PubMed  Google Scholar 

  2. Ghosh SS, Gopinath P, Ramesh A . Adenoviral vectors: a promising tool for gene therapy. Appl Biochem Biotechnol 2006; 133: 9–29.

    Article  CAS  PubMed  Google Scholar 

  3. Keriel A, Rene C, Galer C, Zabner J, Kremer EJ . Canine adenovirus vectors for lung-directed gene transfer: efficacy, immune response, and duration of transgene expression using helper-dependent vectors. J Virol 2006; 80: 1487–1496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nilsson M, Ljungberg J, Richter J, Kiefer T, Magnusson M, Lieber A et al. Development of an adenoviral vector system with adenovirus serotype 35 tropism; efficient transient gene transfer into primary malignant hematopoietic cells. J Gene Med 2004; 6: 631–641.

    Article  CAS  PubMed  Google Scholar 

  5. Mailly L, Renaut L, Rogee S, Grellier E, D'Halluin JC, Colin M . Improved gene delivery to B lymphocytes using a modified adenovirus vector targeting CD21. Mol Ther 2006; 14: 293–304.

    Article  CAS  PubMed  Google Scholar 

  6. Mizuguchi H, Hayakawa T . Targeted adenovirus vectors. Hum Gene Ther 2004; 15: 1034–1044.

    Article  CAS  PubMed  Google Scholar 

  7. Campbell M, Qu S, Wells S, Sugandha H, Jensen RA . An adenoviral vector containing an arg-gly-asp (RGD) motif in the fiber knob enhances protein product levels from transgenes refractory to expression. Cancer Gene Ther 2003; 10: 559–570.

    Article  CAS  PubMed  Google Scholar 

  8. Kurachi S, Koizumi N, Sakurai F, Kawabata K, Sakurai H, Nakagawa S et al. Characterization of capsid-modified adenovirus vectors containing heterologous peptides in the fiber knob, protein IX, or hexon. Gene Therapy 2007; 14: 266–274.

    Article  CAS  PubMed  Google Scholar 

  9. Hartigan-O'Connor D, Barjot C, Salvatori G, Chamberlain JS . Generation and growth of gutted adenoviral vectors. Methods Enzymol 2002; 346: 224–246.

    Article  CAS  PubMed  Google Scholar 

  10. Fouletier-Dilling CM, Bosch P, Davis AR, Shafer JA, Stice SL, Gugala Z et al. Novel compound enables high-level adenovirus transduction in the absence of an adenovirus-specific receptor. Hum Gene Ther 2005; 16: 1287–1297.

    Article  CAS  PubMed  Google Scholar 

  11. Arcasoy SM, Latoche JD, Gondor M, Pitt BR, Pilewski JM . Polycations increase the efficiency of adenovirus-mediated gene transfer to epithelial and endothelial cells in vitro. Gene Therapy 1997; 4: 32–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Fasbender A, Lee JH, Walters RW, Moninger TO, Zabner J, Welsh MJ . Incorporation of adenovirus in calcium phosphate precipitates enhances gene transfer to airway epithelia in vitro and in vivo. J Clin Invest 1998; 102: 184–193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Toyoda K, Andresen JJ, Zabner J, Faraci FM, Heistad DD . Calcium phosphate precipitates augment adenovirus-mediated gene transfer to blood vessels in vitro and in vivo. Gene Therapy 2000; 7: 1284–1291.

    Article  CAS  PubMed  Google Scholar 

  14. Evans CH . Biochemistry of the Lanthanides. Plenum Press: New York, 1990.

    Book  Google Scholar 

  15. Shea CM, Edgar CM, Einhorn TA, Gerstenfeld LC . BMP treatment of C3H10T1/2 mesenchymal stem cells induces both chondrogenesis and osteogenesis. J Cell Biochem 2003; 90: 1112–1127.

    Article  CAS  PubMed  Google Scholar 

  16. Dinarello CA . The IL-1 family and inflammatory diseases. Clin Exp Rheumatol 2002; 20: S1–S13.

    CAS  PubMed  Google Scholar 

  17. Arend WP, Evans CH . Interleukin-1 receptor antagonist. In: Thompson AW and Lotze MT (eds). The Cytokine Handbook. Academic Press: London, 2003.

    Google Scholar 

  18. Balk ML, Bray J, Day C, Epperly M, Greenberger J, Evans CH et al. Effect of rhBMP-2 on the osteogenic potential of bone marrow stromal cells from an osteogenesis imperfecta mouse (oim). Bone 1997; 21: 7–15.

    Article  CAS  PubMed  Google Scholar 

  19. Gouze JN, Gouze E, Palmer GD, Liew VS, Pascher A, Betz OB et al. A comparative study of the inhibitory effects of interleukin-1 receptor antagonist following administration as a recombinant protein or by gene transfer. Arthritis Res Ther 2003; 5: R301–R309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gouze E, Pawliuk R, Pilapil C, Gouze JN, Fleet C, Palmer GD et al. In vivo gene delivery to synovium by lentiviral vectors. Mol Ther 2002; 5: 397–404.

    Article  CAS  PubMed  Google Scholar 

  21. Kawabata K, Sakurai F, Koizumi N, Hayakawa T, Mizuguchi H . Adenovirus vector-mediated gene transfer into stem cells. Mol Pharmacol 2006; 3: 95–103.

    Article  CAS  Google Scholar 

  22. Bosch P, Fouletier-Dilling C, Olmsted-Davis EA, Davis AR, Stice SL . Efficient adenoviral-mediated gene delivery into porcine mesenchymal stem cells. Mol Reprod Dev 2006; 73: 1393–1403.

    Article  CAS  PubMed  Google Scholar 

  23. Hardy S, Kitamura M, Harris-Stansil T, Dai Y, Phipps ML . Construction of adenovirus vectors through Cre-lox recombination. J Virol 1997; 71: 1842–1849.

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Palmer GD, Gouze E, Gouze JN, Betz OB, Evans CH, Ghivizzani SC . Gene transfer to articular chondrocytes with recombinant adenovirus. Methods Mol Biol 2003; 215: 235–246.

    CAS  PubMed  Google Scholar 

  25. Reznikoff CA, Brankow DW, Heidelberger C . Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res 1973; 33: 3231–3238.

    CAS  PubMed  Google Scholar 

  26. Gouze JN, Stoddart MJ, Gouze E, Palmer GD, Ghivizzani SC, Grodzinsky AJ et al. In vitro gene transfer to chondrocytes and synovial fibroblasts by adenoviral vectors. Methods Mol Med 2004; 100: 147–164.

    CAS  PubMed  Google Scholar 

  27. Tuli R, Seghatoleslami MR, Tuli S, Wang ML, Hozack WJ, Manner PA et al. A simple, high-yield method for obtaining multipotential mesenchymal progenitor cells from trabecular bone. Mol Biotechnol 2003; 23: 37–49.

    Article  CAS  PubMed  Google Scholar 

  28. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR . Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 1982; 126: 131–138.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was partially supported by R21 AR050705 from NIAMS.

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Author notes

  1. G D Palmer

    Present address: 2Current address: Division of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine, New York, NY 10003, USA.,

  2. M J Stoddart

    Present address: 3Current address: AO Research Institute, Davos, Switzerland.,

  3. E Gouze, J-N Gouze & S C Ghivizzani

    Present address: 4Current address: Department of Orthopaedics and Rehabilitation, University of Florida College of Medicine, Gainesville, FL 32610, USA.,

Authors and Affiliations

  1. Center for Molecular Orthopaedics, Harvard Medical School, Boston, MA, USA

    G D Palmer, M J Stoddart, E Gouze, J-N Gouze, S C Ghivizzani, R M Porter & C H Evans

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  1. G D Palmer
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Correspondence to C H Evans.

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Palmer, G., Stoddart, M., Gouze, E. et al. A simple, lanthanide-based method to enhance the transduction efficiency of adenovirus vectors. Gene Ther 15, 357–363 (2008). https://doi.org/10.1038/sj.gt.3303092

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