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Intelligent polymers as nonviral vectors

Gene Therapy volume 12, pages S139–S145 (2005)Cite this article

Abstract

The successful gene therapy largely depends on the vector type that allows a selective and efficient gene delivery to target cells with minimal toxicity. Nonviral vectors are much safer and cheaper, can be produced easily in large quantities, and have higher genetic material carrying capacity. However, they are generally less efficient in delivering DNA and initiating gene expression as compared to viral vectors, particularly when used in vivo. As nonviral vectors, polycations may work well for efficient cell uptake and endosomal escape, because they do form compact and smaller complexes with plasmid DNA and carry amine groups, which give positive charge and buffering ability that allows safe escape from endosome/lysosome. However, this is a disadvantage in the following step, which is releasing the plasmid DNA within the cytosol. In order to initiate transcription and enhance gene expression, the polymer/plasmid complex should dissociate after releasing from endosome safely and effectively. There are also other limitations with some of the polycationic carriers, for example, aggregation, toxicity, etc. Intelligent polymers, also called as ‘stimuli responsive polymers’, have a great potential as nonviral vectors to obtain site-, timing-, and duration period-specific gene expression, which is already exhibited in recent studies that are briefly summarized here.

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References

  1. Choi YHF et al. In vivo delivery to tumors of DNA complexed with linear poliethylenimine. Hum Gene Ther 1999; 10: 2657–2665.

    Article  CAS  PubMed  Google Scholar 

  2. Bielinska AU, Kukowskalatallo JF, Baker JR . Regulation of gene expression with double-stranded phosphothioate oligoncleotides. Biochim Biophys Acta 1997; 1353: 180–190.

    Article  CAS  PubMed  Google Scholar 

  3. Boussif O, Zanta MA, Behr JP . Optimized galenics improve in vitro gene transfer with cationic molecules up to 1000-fold. Gene Therapy 1996; 3: 1074–1080.

    CAS  PubMed  Google Scholar 

  4. Erbacher P et al. Chitosan-based vector/DNA complexes for gene delivery: biophysical characteristics and transfection ability. Pharm Res 1998; 15: 1332–1339.

    Article  CAS  PubMed  Google Scholar 

  5. Ferrari S et al. ExGen 500 is an efficient vector for gene delivery to lung epithelial cells in vitro and in vivo. Gene Therapy 1997; 4: 1100–1106.

    Article  CAS  PubMed  Google Scholar 

  6. Smith LC et al. Humoral and cellular immune responses of dogs immunized with a nucleic acid vaccine encoding human carcinoembryonic antigen. Adv Drug Deliv Rev 1998; 30: 115–131.

    Article  CAS  PubMed  Google Scholar 

  7. Godbey WT, Wu KK, Mikos AG . Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery. Proc Natl Acad Sci USA 1999; 96: 5177–5181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ogris M et al. PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Therapy 1999; 6: 4595–4605.

    Article  Google Scholar 

  9. Kwoh DY et al. Stabilization of poly-L-lysine /DNA polyplexes for in vivo gene delivery to the liver. Biochim Biophys Acta 1999; 1444: 171–190.

    Article  CAS  PubMed  Google Scholar 

  10. Richardson SCW, Kolbe HVJ, Duncan R . Potential of low molecular mass chitosan as a DNA delivery system: biocompatibility, body distribution and ability to complex and protect DNA. Int J Pharm 1999; 178: 231–243.

    Article  CAS  PubMed  Google Scholar 

  11. Fischer D et al. A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity. Pharm Res 1999; 16: 1273–1279.

    Article  CAS  PubMed  Google Scholar 

  12. Hwang S, Bellocq N, Davis ME . Effects of structure of β-cyclodextrin-containing polymers on gene delivery. Bioconjugate Chem 2001; 12: 280–290.

    Article  CAS  Google Scholar 

  13. Yokoyama M . Gene delivery using temperature responsive polymeric carriers. Drug Discovery Today 2002; 7: 426–432.

    Article  CAS  PubMed  Google Scholar 

  14. Hoffman AS . Bioconjugates of intelligent polymers and recognition proteins for use in diagnostics and affinity separations. Clin Chem 2000; 46: 1478–1486.

    CAS  PubMed  Google Scholar 

  15. Shimoboji T et al. Photoresponsive polymer-enzyme switches. Proc Natl Acad Sci USA 2002; 99: 16592–16596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hinrichs WLJ et al. Thermosensitive polymers as carriers for DNA delivery. J Control Release 1999; 60: 249–259.

    Article  CAS  PubMed  Google Scholar 

  17. Kurisawa M, Yokoyama M, Okano T . Gene expression control by temperature with thermo-responsive polymeric gene carriers. J Control Release 2000; 69: 127–137.

    Article  CAS  PubMed  Google Scholar 

  18. Yokoyama M, Kurisawa M, Okano T . Influential factors on temperature-controlled gene expression using thermoresponsive polymeric gene carriers. J Artif Organs 2001; 4: 138–145.

    Article  CAS  Google Scholar 

  19. Twaites B et al. Thermo and pH responsive polymers as gene delivery vectors:effect of polymer architecture on DNA complexation in vitro. J Control Release 2004; 97: 551–566.

    Article  CAS  PubMed  Google Scholar 

  20. Nagasaki T et al. Synthesis of a novel water-soluble poliazobenzene dendrimer and photoregulation of affinity toward DNA. Mol Cryst Liq Cryst 2000; 345: 227–232.

    Article  CAS  Google Scholar 

  21. Nagasaki T, Wada K, Tamagaki S . Photo-enhancement of transfection efficiency with a novel azobenzene-based cationic lipid. Chem Lett 2003; 32: 88–89.

    Article  CAS  Google Scholar 

  22. Berg K et al. Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. Cancer Res 1999; 59: 1180–1183.

    CAS  PubMed  Google Scholar 

  23. Hogset A et al. Photochemical transfection: a new technology for light-induced, site-directed gene delivery. Hum Gene Ther 2000; 11: 869–880.

    Article  CAS  PubMed  Google Scholar 

  24. Prasmickaite L et al. Role of endosomes in gene transfection mediated by photochemical internalisation(PCI). J Gene Med 2000; 2: 477–488.

    Article  CAS  PubMed  Google Scholar 

  25. Prasmickaite L, Hogset A, Berg K . Evaluation of different photosensitizers for use in photochemical gene transfection. Photochem Photobiol 2001; 73: 388–395.

    Article  CAS  PubMed  Google Scholar 

  26. Hogset A et al. Light-induced adenovirus gene transfer, an efficient and specific gene delivery technology for cancer gene therapy. Cancer Gene Ther 2002; 9: 365–371.

    Article  CAS  PubMed  Google Scholar 

  27. Brunner S et al. Cell cycle dependence of gene transfer by lipoplex, polyplex and recombinant adenovirus. Gene Therapy 2000; 7: 401–407.

    Article  CAS  PubMed  Google Scholar 

  28. Prasmickaitea L, Hogset A, Berg K . The role of the cell cycle on the efficiency of photochemical gene transfection. Biochim Biophys Acta 2002; 1570: 210–218.

    Article  Google Scholar 

  29. Dinçer S, Tuncel A, Piskin E . Potential gene delivery vector: N-isopropylacrylamide-ethyleneimine block copolymers. Macromol Chem Phys 2002; 203: 1460–1465.

    Article  Google Scholar 

  30. Türk M et al. In vitro transfection of HeLa cells with temperature sensitive polycationic copolymers. J Control Release 2004; 96: 325–340.

    Article  PubMed  Google Scholar 

  31. Türk M, Dinçer S, Pişkin E . In vitro transfection of smooth muscle cells with smart polycationic macromolecules. J Biomat Sci: Polym Ed, submitted, 2005.

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Acknowledgements

Professor Erhan Pişkin is supported by the Turkish Academy of Sciences as a full member.

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Authors and Affiliations

  1. Chemical Engineering Department and Bioengineering Division, Hacettepe University, Ankara, Turkey

    S Dinçer, M Türk & E Pişkin

  2. TÜBİ TAK-ÜSAM-Biyomedtek, Hacettepe University, Ankara, Turkey

    S Dinçer, M Türk & E Pişkin

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Dinçer, S., Türk, M. & Pişkin, E. Intelligent polymers as nonviral vectors. Gene Ther 12 (Suppl 1), S139–S145 (2005). https://doi.org/10.1038/sj.gt.3302628

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