Abstract
A novel non-viral gene delivery system comprised of a DNA/PEI/Alginate (DPA) polyplex was prepared and assessedin vitro andin vivo. Coating the positively charged DNA/PEI (DP) complex with a polyanion resulted in a high level ofin vitro reporter gene transfection in the presence of 50 vol% serum due to the minimized cytotoxicity of PEI and the reduced nonspecific interactions with serum components. Among the tested anionic polymers, which included sodium alginate, poly(methacrylic acid) and poly(acrylic acid), the sodium alginate showed the highest gene transfection efficiency. The DPA polyplex also showed a reduced level of erythrocyte aggregation in target cells when compared with the DP complex. According toin vivo studies in which reporter genes encoding green fluorescent protein (GFP) and luciferase were used, injection of the DPA polyplex into tumor cells in six week old female C57/BL6 mice resulted in a much higher level of GFP expression and approximately 7 fold higher luciferase expression than treatment with the DP complex. Taken together, these results demonstrated that the anionic alginate coating of the DP complex contributed to efficient gene deliveryin vitro andin vivo.
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Boussif, O., F. Lezoualc'h, M. A. Zanta, M. D. Mergny, D. Scherman, B. Demeneix, and J. P. Behr (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture andin vivo: polyethylenimine.Proc. Natl. Acad. Sci. USA 92: 7297–7301.
Park, H. J., C. M. Lee, Y. B. Lee, and K. Y. Lee (2006) Controlled release of cyclosporin a from liposomes-in-licrospheres as an oral delivery system.Biotechnol. Bioprocess Eng. 11: 526–529.
Bae, J. W., J. H. Han, M. S. Park, S. G. Lee, E. Y. Lee, Y. J. Jeong, and S. Park (2006) Development of recombinantPseudomonas putida containing homologous styrene monooxygenase genes for the production of (S)-styrene oxide.Biotechnol. Bioprocess Eng. 11: 530–537.
Boussif, O., M. A. Zanta, and J. P. Behr (1996) Optimized galenics improvein vitro gene transfer with cationic molecules up to 1000-fold.Gene Ther. 3: 1074–1080.
Chollet, P., M. C. Favrot, A. Hurbin, and J. L. Coll (2002) Side-effects of a systemic injection of linear polyethylenimine-DNA complexes.J. Gene Med. 4: 84–91.
Oupicky, D., M. Ogris, K. A. Howard, P. R. Dash, K. Ulbrich, and L. W. Seymour (2002) Importance of lateral and steric stabilization of polyelectrolyte gene delivery vectors for extended systemic circulation.Mol. Ther. 5: 463–472.
Trubetskoy, V. S., S. C. Wong, V. Subbotin, V. G. Budker, A. Loomis, J. E. Hagstrom, and J. A. Wolff (2003) Recharging cationic DNA complexes with highly charged polyanions forin vitro andin vivo gene delivery.Gene Ther. 10: 261–271.
Ahn, C. H., S. Y. Chae, Y. H. Bae, and S. W. Kim (2002) Biodegradable poly(ethyleneimine) for plasmid DNA delivery.J. Control. Rel. 80: 273–282.
Tseng, W. C., and C. M. Jong (2003) Improved stability of polycationic vector by dextran-grafted branched polyethylenimine.Biomacromolecules 4: 1277–1284.
Patnaik, S., A. Aggarwal, S. Nimesh, A. Goel, M. Ganguli, N. Saini, Y. Singh, and K. C. Gupta (2006) PEI-alginate nanocomposites as efficientin vitro gene transfection agents.J. Control. Rel. 114: 398–409.
Mittal, S. K., N. Aggarwala, G. Sailaja, A. van Olphen, H. HogenEsch, A. North, J. Hays, and S. Moffatt (2000) Immunization with DNA, adenovirus or both in biodegradable alginate microspheres: effect of route of inoculation on immune response,Vaccine 19: 253–263.
Hahn, S. K., R. Ohri, and C. M. Giachelli (2005) Anticalcification of bovine pericardium for bioprosthetic heart valves after surface modification with hyaluronic acid derivatives.Biotechnol. Bioprocess Eng. 10: 218–224.
Ossevoort, M. A., M. C. Feltkamp, K. J. van Veen, C. J. Melief, and W. M. Kast (1995) Dendritic cells as carriers for a cytotoxic T-lymphocyte epitope-based peptide vaccine in protection against a human papillonavirus type 16-induced tumor.J. Immunother Emphasis Tumor Immunol. 18: 86–94.
You, J. O., and C. A. Peng (2005) Phagocytosis-mediated retroviral transduction: co-internalization of deactivated retrovirus and calcium-alginate microspheres by macriophages.J. Gene Med. 7: 398–406.
Jiang, G., S. H. Min, M. N. Kim, D. C. Lee, M. J. Lim, and Y. I. Yeom (2006) Alginate/PEI/DNA polyplexes: a new gene delivery system.Yao Xue Xue Bao 41: 439–445.
Kyriakides, T. R., C. Y. Cheung, N. Murthy, P. Bornstein, P. S. Stayton, and A. S. Hoffman (2002) pH-Sensitive polymer that enhance intracellular drug deliveryin vivo.J. Control. Rel. 78: 295–303.
Ogris, M., S. Brunner, S. Schuller, R. Kircheis, and E. Wagner (1999) PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery.Gene Ther. 6: 595–605.
Kircheis, R., L. Wightman, and E. Wagner (2001) Design and gene delivery activity of modified polyethylenimines.Adv. Drug Deliv. Rev. 53: 341–358.
Tey, B. T., and M. Al-Rubeai (2005) Bcl-2 over-expression reduced the serum dependency and improved the nutrient metabolism in a NS0 cells culture.Biotechnol. Bioprocess Eng. 10: 254–261.
Park, H., S. Ahn, and T. Choe (2006) Change of insulin-like growth factor gene expression in Chinese hamster ovary cells cultured in serum-free media.Biotechnol. Bioprocess Eng. 11: 319–324.
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Jiang, G., Min, SH., Oh, E.J. et al. DNA/PEI/Alginate polyplex as an efficientin vivo gene delivery system. Biotechnol. Bioprocess Eng. 12, 684–689 (2007). https://doi.org/10.1007/BF02931086
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DOI: https://doi.org/10.1007/BF02931086