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Recombinant Histones as an Instrument for the Delivery of Nucleic Acids into Eukaryotic Cells

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Abstract

Naturally occurring positively charged proteins can be promising carriers for nucleic acid transport in gene therapy. The most attractive alternative among them is histones. In this work, we describe expression and purification of recombinant human histones H2A and H2B and of chimeric histone H2A with HIV-1 TAT fragment (TAT-peptide). The proposed method of purification of histone proteins can significantly reduce the content of bacterial endotoxins in the target preparation, which makes it possible to use these proteins in in vivo experiments. The transfection ability of plasmid DNA complexes with core histones H2A and H2B and the chimeric histone was demonstrated. A highly specific and efficient transfection of human HT1080 cell line with the use of histones H2A and H2B was detected, whereas transfection by plasmid DNA complexes with chimeric H2A-TAT protein was observed for many cell lines.

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REFERENCES

  1. Bakhtiar, A., Sayyad, M., Rosli, R., Maruyama, A., and Chowdhury, E.H., Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy, Curr. Gene Ther., 2014, vol. 14, pp. 247–257.

    Article  CAS  PubMed  Google Scholar 

  2. Nayerossadat, N., Maedeh, T., and Ali, P.A., Viral and non-viral delivery systems for gene delivery, Adv. Biomed. Res., 2012, vol. 1, p. 27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Berry, G.E. and Asokan, A., Cellular transduction mechanisms of adeno-associated viral vectors, Curr. Opin. Virol., 2016, vol. 21, pp. 54–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ibraheem, D., Elaissari, A., and Fessi, H., Gene therapy and DNA delivery systems, Int. J. Pharm., 2014, vol. 459, pp. 70–83.

    Article  CAS  PubMed  Google Scholar 

  5. Lukashev, A.N. and Zamyatnin, A.A., Jr., Viral vectors for gene therapy: Current state and clinical perspectives, Biochemistry (Moscow), 2016, vol. 81, pp. 700–708.

    CAS  PubMed  Google Scholar 

  6. Ramamoorth, M. and Narvekar, A., Non-viral vectors in gene therapy–an overview, J. Clin. Diagn. Res., 2015, vol. 9, pp. GE01–GE06.

    PubMed  PubMed Central  Google Scholar 

  7. Slivac, I., Guay, D., Mangion, M., Champeil, J., and Gaillet, B., Non-viral nucleic acid delivery methods, Expert Opin. Biol. Ther., 2017, vol. 17, pp. 105–118.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang, C., Jin, R., Zhao, P., and Lin, C., A family of cationic polyamides for in vitro and in vivo gene transfection, Acta Biomater., 2015, vol. 22, pp. 120–130.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang, P. and Wagner, E., History of polymeric gene delivery systems, Top. Curr. Chem. (Cham), 2017, vol. 375, p. 26.

    Article  CAS  Google Scholar 

  10. Stanzl, E.G., Trantow, B.M., Vargas, J.R., and Wender, P.A., Fifteen years of cell-penetrating, guanidinium-rich molecular transporters: basic science, research tools, and clinical applications, Acc. Chem. Res., 2013, vol. 46, pp. 2944–2954.

    Article  CAS  PubMed  Google Scholar 

  11. Kouchakzadeh, H. and Abbas Shojaosadati, S., The prominent role of protein-based delivery systems on the development of cancer treatment, Curr. Pharm. Des., 2016, vol. 22, pp. 3455–3465.

    Article  CAS  PubMed  Google Scholar 

  12. Komin, A., Russell, L.M., Hristova, K.A., and Searson, P.C., Peptide-based strategies for enhanced cell uptake, transcellular transport, and circulation: Mechanisms and challenges, Adv. Drug Delivery Rev., 2017, vols. 110–111, pp. 52–64.

    Article  CAS  Google Scholar 

  13. Radis-Baptista, G., Campelo, I.S., Morlighem, J.R.L., et al., Cell-penetrating peptides (CPPs): From delivery of nucleic acids and antigens to transduction of engineered nucleases for application in transgenesis, J. Biotechnol., 2017, vol. 252, pp. 15–26.

    Article  CAS  PubMed  Google Scholar 

  14. Balicki, D. and Beutler, E., Histone H2A significantly enhances in vitro DNA transfection, Mol. Med., 1997, vol. 3, pp. 782–787.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Puebla, I., Esseghir, S., Mortlock, A., et al., A recombinant H1 histone-based system for efficient delivery of nucleic acids, J. Biotechnol., 2003, vol. 105, pp. 215–226.

    Article  CAS  PubMed  Google Scholar 

  16. Kaouass, M., Beaulieu, R., and Balicki, D., Histonefection: Novel and potent non-viral gene delivery, J. Controlled Release, 2006, vol. 113, pp. 245–254.

    Article  CAS  Google Scholar 

  17. Reilly, M.J., Larsen, J.D., and Sullivan, M.O., Histone H3 tail peptides and poly(ethylenimine) have synergistic effects for gene delivery, Mol. Pharm., 2012, vol. 9, pp. 1031–1040.

    Article  CAS  PubMed  Google Scholar 

  18. Hariton-Gazal, E., Rosenbluh, J., Graessmann, A., et al., Direct translocation of histone molecules across cell membranes, J. Cell Sci., 2003, vol. 116, pp. 4577–4586.

    Article  CAS  PubMed  Google Scholar 

  19. Wagstaff, K.M., Glover, D.J., Tremethick, D.J., and Jans, D.A., Histone-mediated transduction as an efficient means for gene delivery, Mol. Ther., 2007, vol. 15, pp. 721–731.

    Article  CAS  PubMed  Google Scholar 

  20. Schneeweiss, A., Buyens, K., Giese, M., et al., Synergistic effects between natural histone mixtures and polyethylenimine in non-viral gene delivery in vitro, Int. J. Pharm., 2010, vol. 400, pp. 86–95.

    Article  CAS  PubMed  Google Scholar 

  21. Torchilin, V.P., Tat peptide-mediated intracellular delivery of pharmaceutical nanocarriers, Adv. Drug Delivery Rev., 2008, vol. 60, pp. 548–558.

    Article  CAS  Google Scholar 

  22. Sawant, R. and Torchilin, V., Intracellular transduction using cell-penetrating peptides, Mol. Biosyst., 2011, vol. 6, pp. 628–640.

    Article  Google Scholar 

  23. Ulasov, A.V., Khramtsov, Y.V., Trusov, G.A., et al., Properties of PEI-based polyplex nanoparticles that correlate with their transfection efficacy, Mol. Ther., 2011, vol. 19, pp. 103–112.

    Article  CAS  PubMed  Google Scholar 

  24. Johns, E.W., The isolation and purification of histones, Methods Cell Biol., 1977, vol. 16, pp. 183–203.

    Article  CAS  PubMed  Google Scholar 

  25. von Holt, C., Brandt, W.F., Greyling, H.J., et al., Isolation and characterization of histones, Methods Enzymol., 1989, vol. 170, pp. 431–523.

    Article  CAS  PubMed  Google Scholar 

  26. Tanaka, Y., Tawaramoto-Sasanuma, M., Kawaguchi, S., et al., Expression and purification of recombinant human histones, Methods, 2004, vol. 33, pp. 3–11.

    Article  CAS  PubMed  Google Scholar 

  27. Shechter, D., Dormann, H.L., Allis, C.D., and Hake, S.B., Extraction, purification and analysis of histones, Nat. Protoc., 2007, vol. 2, pp. 1445–1457.

    Article  CAS  PubMed  Google Scholar 

  28. Gusarov, D.A., Methods for bacterial endotoxines removal from protein solutions, Biopharm. J., 2009, vol. 1, no. 3, pp. 10–17.

    CAS  Google Scholar 

  29. Gusarov, D., Sokolova, I., Vorobjeva, T., and Brykova, N., Positively charged proteins: Separation and depyrogenation by means of HPLC (by the example of recombinant histone H1.3 variant), Biopharm. J., 2011, vol. 3, pp. 16–23.

    CAS  Google Scholar 

  30. Klinker, H., Haas, C., Harrer, N., Becker, P.B., and Mueller-Planitz, F., Rapid purification of recombinant histones, PLoS One, 2014, vol. 9, p. e104029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fujitani, H. and Holoubek, V., Recovery of histones by acid extraction from chromatin and from artificial DNA-histone complex, Tex. Rep. Biol. Med., 1974, vol. 32, pp. 461–478.

    CAS  PubMed  Google Scholar 

  32. Kawashige, M., Sendo, T., Otsubo, K., et al., Quality evaluation of commercial lyophilized human growth hormone preparations, Biol. Pharm. Bull., 1995, vol. 18, pp. 1793–1796.

    Article  CAS  PubMed  Google Scholar 

  33. Ahangari, G., Ostadali, M.R., Rabani, A., et al., Growth hormone antibodies formation in patients treated with recombinant human growth hormone, Int. J. Immunopathol. Pharmacol., 2004, vol. 17, pp. 33–38.

    Article  CAS  PubMed  Google Scholar 

  34. Balicki, D., Reisfeld, R.A., Pertl, U., et al., Histone H2A-mediated transient cytokine gene delivery induces efficient antitumor responses in murine neuroblastoma, Proc. Natl. Acad. Sci. U. S. A., 2000, vol. 97, pp. 11 500–11 504.

    Article  Google Scholar 

  35. Torchilin, V.P., Cell penetrating peptide-modified pharmaceutical nanocarriers for intracellular drug and gene delivery, Biopolymers, 2008, vol. 90, pp. 604–610.

    Article  CAS  PubMed  Google Scholar 

Download references

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Correspondence to M. V. Zinovyeva.

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Translated by I. N. Shipounova

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Zinovyeva, M.V., Sass, A.V., Vvedensky, A.V. et al. Recombinant Histones as an Instrument for the Delivery of Nucleic Acids into Eukaryotic Cells. Mol. Genet. Microbiol. Virol. 33, 187–194 (2018). https://doi.org/10.3103/S0891416818030072

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  • DOI: https://doi.org/10.3103/S0891416818030072

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