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Targeted gene delivery: the role of peptide nucleic acid

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Abstract

Receptor-mediated endocytosis can be exploited to achieve efficient cell-specific gene delivery. Our laboratory has used two approaches for targeted gene delivery. One uses polycation as a carrier for plasmid DNA and the other uses peptide nucleic acid (PNA) as a carrier. Targeted gene delivery using polycation carriers has been widely utilized with some success. This approach mainly suffers from large particle size and non-specific interaction with blood components. These drawbacks have limited use of this type of vector for in vivoapplications. Using PNA as a carrier, on the other hand, allows for smaller particle size and less non-specific interactions. The stability of this vector in the circulation may be a limiting factor. In addition, both types of vectorlack mechanisms for endosome escape and nuclear transport. In this chapter, current developments and uses for targeted gene delivery of each approach are reviewed.

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References

  • Boussif, O., Lezoualc'h, F., Zanta, M.A., Mergny, M.D., Scher-man, D., Demeneix, B. and Behr, J.P. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc. Natl. Acad. Sci. U.S.A., 92 (1995) 7297.

    CAS  PubMed  Google Scholar 

  • Budker, V., Budker, T., Zhang, G., Subbotin, V., Loomis, A. and Wolff, J.A. Hypothesis: naked plasmid DNA is taken up by cells in vivoby a receptor-mediated process. J. Gene Med., 2 (2000) 76.

    Article  CAS  PubMed  Google Scholar 

  • Budker, V., Zhang, G., Danko, I., Williams, P. and Wolff, J. The efficient expression of intravascularly delivered DNA in rat muscle. Gene Ther., 5 (1998) 272.

    Article  CAS  PubMed  Google Scholar 

  • Budker, V., Zhang, G., Knechtle, S. and Wolff, J.A. Naked DNA delivered intraportally expresses efficiently in hepatocytes. Gene Ther., 3 (1996) 593.

    CAS  PubMed  Google Scholar 

  • Buschle, M., Cotten, M., Kirlappos, H., Mechtler, K., Schaffner, G., Zauner, W., Birnstiel, M.L. and Wagner, E. Receptor-mediated gene transfer into human T lymphocytes via binding of DNA/CD3 antibody particles to the CD3 T cell receptor complex. Hum. Gene Ther., 6 (1995) 753.

    CAS  PubMed  Google Scholar 

  • Chen, J., Gamou, S., Takayanagi, A., Ohtake, Y., Ohtsubo, M. and Shimizu, N. Targeted in vivodelivery of therapeutic gene into experimental squamous cell carcinomas using anti-epidermal growth factor receptor antibody: immunogene approach. Hum. Gene Ther., 9 (1998) 2673.

    CAS  PubMed  Google Scholar 

  • Choi, Y.H., Liu, F., Park, J.S. and Kim, S.W. Lactose-poly(ethylene glycol)-grafted poly-L-lysine as hepatoma cell-tapgeted gene carrier. Bioconjug. Chem., 9 (1998) 708.

    Article  CAS  PubMed  Google Scholar 

  • Cotten, M., Langle-Rouault, F., Kirlappos, H., Wagner, E., Mechtler, K., Zenke, M., Beug, H. and Birnstiel, M.L. Transferrin-polycation-mediated introduction of DNA into hu-man leukemic cells: stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels. Proc. Natl. Acad. Sci. U.S.A., 87 (1990) 4033.

    CAS  PubMed  Google Scholar 

  • Demidov, V.V., Yavnilovich, M.V., Belotserkovskii, B.P., Frank-Kamenetskii, M.D. and Nielsen, P.E. Kinetics and mechanism of polyamide ('peptide') nucleic acid binding to duplex DNA. Proc. Natl. Acad. Sci. U.S.A., 92 (1995) 2637.

    CAS  PubMed  Google Scholar 

  • Diebold, S.S., Kursa, M., Wagner, E., Cotten, M. and Zenke, M. Mannose polyethylenimine conjugates for targeted DNA delivery into dendritic cells. J. Biol. Chem., 274 (1999) 19087.

    Article  CAS  PubMed  Google Scholar 

  • Egholm, M., Buchardt, O., Christensen, L., Behrens, C., Freier, S.M., Driver, D.A., Berg, R.H., Kim, S.K., Norden, B. and Nielsen, P.E. PNA hybridizes to complementary oligonuc-leotides obeying the Watson-Crick hydrogen-bonding rules [see comments]. Nature, 365 (1993) 566.

    Article  CAS  PubMed  Google Scholar 

  • Erbacher, P., Bousser, M.T., Raimond, J., Monsigny, M., Midoux, P. and Roche, A.C. Gene transfer by DNA/glycosylated polylysine complexes into human blood monocyte-derived macrophages. Hum. Gene Ther., 7 (1996) 721.

    CAS  PubMed  Google Scholar 

  • Erbacher, P., Remy, J.S. and Behr, J.P. Gene transfer with syn-thetic virus-like particles via the integrin-mediated endocytosis pathway. Gene Ther., 6 (1999) 138.

    Article  CAS  PubMed  Google Scholar 

  • Ferkol, T., Perales, J.C., Eckman, E., Kaetzel, C.S., Hanson, R.W.and Davis, P.B. Gene transfer into the airway epithelium of animals by targeting the polymeric immunoglobulin receptor. J. Clin. Invest., 95 (1995) 493.

    CAS  PubMed  Google Scholar 

  • Ferkol, T., Perales, J.C., Mularo, F. and Hanson, R.W. Receptor-mediated gene transfer into macrophages. Proc. Natl. Acad. Sci. U.S.A., 93 (1996) 101.

    Article  CAS  PubMed  Google Scholar 

  • Hickman, M.A., Malone, R.W., Lehmann-Bruinsma, K., Sih, T.R., Knoell, D., Szoka, F.C., Walzem, R., Carlson, D.M. and Powell, J.S. Gene expression following direct injection of DNA into liver. Hum. Gene Ther., 5 (1994) 1477.

    CAS  PubMed  Google Scholar 

  • Hoganson, D.K., Chandler, L.A., Fleurbaaij, G.A., Ying, W., Black, M.E., Doukas, J., Pierce, G.F., Baird, A. and Sosnowski, B.A. Targeted delivery of DNA encoding cytotoxic proteins through high-affinity fibroblast growth factor receptors. Hum. Gene Ther., 9 (1998) 2565.

    Article  CAS  PubMed  Google Scholar 

  • Kircheis, R., Kichler, A., Wallner, G., Kursa, M., Ogris, M., Felzmann, T., Buchberger, M. and Wagner, E. Coupling of cell-binding ligands to polyethylenimine for targeted gene delivery. Gene Ther., 4 (1997) 409.

    Article  CAS  PubMed  Google Scholar 

  • Li, S., Tseng, W.C., Stolz, D.B., Wu, S.P., Watkins, S.C. and Huang, L. Dynamic changes in the characteristics of cationic lipidic vec-tors after exposure to mouse serum: implications for intravenous lipofection. Gene Ther., 6 (1999) 585.

    CAS  PubMed  Google Scholar 

  • Liang, K.W., Hoffman, E.P. and Huang, L. Targeted delivery of plas-mid DNA to myogenic cells via transferrin-conjugated peptide nucleic acid. Mol. Ther., 1 (2000) 236.

    Article  CAS  PubMed  Google Scholar 

  • Lin, H., Parmacek, M.S., Morle, G., Bolling, S. and Leiden, J.M. Expression of recombinant genes in myocardium in vivoafter direct injection of DNA. Circulation, 82 (1990) 2217.

    CAS  PubMed  Google Scholar 

  • Liu, F., Song, Y. and Liu, D. Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Ther., 6 (1999) 1258.

    CAS  PubMed  Google Scholar 

  • Mahato, R.I., Rolland, A. and Tomlinson, E. Cationic lipid-based gene delivery systems: pharmaceutical perspectives. Pharm. Res., 14 (1997) 853.

    Article  CAS  PubMed  Google Scholar 

  • McLean, J.W., Fox, E.A., Baluk, P., Bolton, P.B., Haskell, A., Pearl-man, R., Thurston, G., Umemoto, E.Y. and McDonald, D.M. Organ-specific endothelial cell uptake of cationic liposome-DNA complexes in mice. Am. J. Physiol., 273 (1997) H387.

  • Meyer, K.B., Thompson, M.M., Levy, M.Y., Barron, L.G. and Szoka, F.C., Jr. Intratracheal gene delivery to the mouse airway: characterization of plasmid DNA expression and pharmacokin-etics. Gene Ther., 2 (1995) 450.

    CAS  PubMed  Google Scholar 

  • Miller, A.D. Retrovirus packaging cells. Hum. Gene Ther., 1 (1990) 5.

    CAS  PubMed  Google Scholar 

  • Nielsen, P.E., Egholm, M., Berg, R.H. and Buchardt, O. Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science, 254 (1991) 1497.

    CAS  PubMed  Google Scholar 

  • Nielsen, P.E., Egholm, M., Berg, R.H. and Buchardt, O. in S.T. Crook and B. Lebleu (eds.), Antisense Research and Application, CRC Press: Boca Raton, Fl., (1993) pp. 363-374.

    Google Scholar 

  • Ogris, M., Brunner, S., Schuller, S., Kircheis, R. and Wagner, E. PEGylated DNA/transferrin-PEI complexes: reduced interac-tion with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther., 6 (1999) 595.

    Article  CAS  PubMed  Google Scholar 

  • Ogris, M., Steinlein, P., Kursa, M., Mechtler, K., Kircheis, R. and Wagner, E. The size of DNA/transferrin-PEI complexes is an im-portant factor for gene expression in cultured cells. Gene Ther., 5 (1998) 1425.

    Article  CAS  PubMed  Google Scholar 

  • Perales, J.C., Ferkol, T., Beegen, H., Ratnoff, O.D. and Hanson, R.W. Gene transfer in vivo: sustained expression and regulation of genes introduced into the liver by receptor-targeted uptake. Proc. Natl. Acad. Sci. U.S.A., 91 (1994) 4086.

    CAS  PubMed  Google Scholar 

  • Plank, C., Mechtler, K., Szoka, F.C. Jr. and Wagner, E. Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery. Hum. Gene Ther., 7 (1996) 1437.

    CAS  PubMed  Google Scholar 

  • Pollard, H., Remy, J.S., Loussouarn, G., Demolombe, S., Behr, J.P. and Escande, D. Polyethylenimine but not cationic lipids pro-motes transgene delivery to the nucleus in mammalian cells. J. Biol. Chem., 273 (1998) 7507.

    Article  CAS  PubMed  Google Scholar 

  • Rybenkov, V.V., Vologodskii, A.V. and Cozzarelli, N.R. The effect of ionic conditions on the conformations of supercoiled DNA. I. Sedimentation analysis. J. Mol. Biol., 267 (1997) 299.

    CAS  PubMed  Google Scholar 

  • Schaffer, D.V., Fidelman, N.A., Dan, N. and Lauffenburger, D.A. Vector unpacking as a potential barrier for receptor-mediated polyplex gene delivery. Biotechnol. Bioeng., 67 (2000) 598.

    Article  CAS  PubMed  Google Scholar 

  • Schaffer, D.V. and Lauffenburger, D.A. Optimization of cell sur-face binding enhances efficiency and specificity of molecular conjugate gene delivery. J. Biol. Chem., 273 (1998) 28004.

    CAS  PubMed  Google Scholar 

  • Sikes, M.L., O'Malley, B.W., Jr., Finegold, M.J. and Ledley, F.D. In vivogene transfer into rabbit thyroid follicular cells by direct DNA injection. Hum. Gene Ther., 5 (1994) 837.

    CAS  PubMed  Google Scholar 

  • Song, Y.K., Liu, F. and Liu, D. Enhanced gene expression in mouse lung by prolonging the retention time of intravenously injected plasmid DNA. Gene Ther., 5 (1998) 1531.

    Article  CAS  PubMed  Google Scholar 

  • Tsan, M.F., White, J.E. and Shepard, B. Lung-specific direct in vivo gene transfer with recombinant plasmid DNA. Am. J. Physiol., 268 (1995) L1052.

    CAS  PubMed  Google Scholar 

  • Wagner, E., Cotten, M., Foisner, R. and Birnstiel, M.L. Transferrin-polycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells. Proc. Natl. Acad. Sci. U.S.A., 88 (1991) 4255.

    CAS  PubMed  Google Scholar 

  • Wagner, E., Zenke, M., Cotten, M., Beug, H. and Birnstiel, M.L. Transferrin-polycation conjugates as carriers for DNA uptake into cells. Proc. Natl. Acad. Sci. U.S.A., 87 (1990) 3410.

    CAS  PubMed  Google Scholar 

  • Wu, C.H. Wilson, J.M. and Wu, G.Y. Targeting genes: delivery and persistent expression of a foreign gene driven by mammalian regulatory elements in vivo. J. Biol. Chem., 264 (1989) 16985.

    CAS  PubMed  Google Scholar 

  • Wu, G.Y. and Wu, C.H. Receptor-mediated in vitro gene transforma-tion by a soluble DNA carrier system. J. Biol. Chem., 262 (1987) 4429.

    CAS  PubMed  Google Scholar 

  • Wu, G.Y. and Wu, C.H. Receptor-mediated gene delivery and expression in vivo. J. Biol. Chem., 263 (1988) 14621.

    CAS  PubMed  Google Scholar 

  • Wu, G.Y. and Wu, C.H. Targeted delivery and expression of foreign genes in hepatocytes. Targeted Diagn. Ther., 4 (1991) 127.

    CAS  PubMed  Google Scholar 

  • Zanta, M.A., Boussif, O., Adib, A. and Behr, J.P. In vitrogene delivery to hepatocytes with galactosylated polyethylenimine. Bioconjug. Chem., 8 (1997) 839.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, G., Vargo, D., Budker, V., Armstrong, N., Knechtle, S. and Wolff, J.A. Expression of naked plasmid DNA injected into the afferent and efferent vessels of rodent and dog livers [see comments]. Hum. Gene Ther., 8 (1997) 1763.

    CAS  PubMed  Google Scholar 

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  1. Center for Pharmacogenetics and Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, 15213, U.S.A

    Kenneth W. Liang, Feng Liu & Leaf Huang

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  1. Kenneth W. Liang
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  2. Feng Liu
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Liang, K.W., Liu, F. & Huang, L. Targeted gene delivery: the role of peptide nucleic acid. Int J Pept Res Ther 10, 161–167 (2003). https://doi.org/10.1007/s10989-004-4922-x

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