Skip to main content

Advertisement

SpringerLink
Log in

Morpholinos and PNAs compared

  • Published:
Letters in Peptide Science Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Liam, G. and Nielsen, P.E. Progress in developing PNA as a gene-targeted drug. Antisense Nucl. Acid Drug Dev., 7 (1997) 431-437.

    Google Scholar 

  2. Nielsen, P. and Egholm, M. (Eds.) Peptide Nucleic Acids. Norfolk: Horizon Scientific Press (1999).

    Google Scholar 

  3. Summerton, J. and Weller, D. Morpholino antisense oli-gomers: design, preparation and properties. Antisense Nuc-leic Acid Drug Dev. 7 (1997) 187-195.

    CAS  Google Scholar 

  4. Summerton, J. Morpholino antisense oligomers: the case for an RNase H-independent structural type. Biochim. Biophys. Acta, 1489 (1999) 141-158.

    CAS  PubMed  Google Scholar 

  5. Summerton, J. (1990) Polynucleotide assay reagent and method. Canadian Patent; 1, 268, 404. Summerton J, Weller D. (1993). Uncharged Morpholino-based polymers having phosphorous containing chiral intersubunit linkages. US Pat-ent; 5, 185, 444.

    Google Scholar 

  6. Website: www.gene-tools.com

  7. Knudsen, H. and Nielsen, P.E. Antisense properties of duplex and triplex forming PNA. Nucl. Acids Res., 24 (1996) 494-500.

    Article  CAS  PubMed  Google Scholar 

  8. Milner, N., Mir, K. and Southern, E. Selecting effective anti-sense reagents on combinatorial oligonucleotide arrays. Nat. Biotechnol., 15 (1997) 537-541.

    Article  CAS  PubMed  Google Scholar 

  9. Ho, S., Bao, Y., Lesher, T., Malhotra, R., Ma, L., Fluharty, S. and Sakai R. Mapping of RNA accessible sites for antisense experiments with oligonucleotide libraries. Nat. Biotechnol. 16 (1998) 59.

    Article  CAS  PubMed  Google Scholar 

  10. Ekker, S. Morphants: a new systematic vertebrate functional genomics approach. Yeast, 17 (2000) 302-306.

    Article  CAS  PubMed  Google Scholar 

  11. Koch, T. PNA oligomer synthesis by BOC chemistry. In: P. Neilsen and M. Egholm (Eds.), Peptide Nucleic Acids. Norfolk: Horizon Scientific Press (1999) 21-37.

    Google Scholar 

  12. Casale, R., Jensen, I.S. and Egholm, M. Synthesis of PNA oligomers by Fmoc Chemistry. In: P. Neilsen and M. Egholm (Eds.), Peptide Nucleic Acids. Norfolk: Horizon Scientific Press (1999) 39-50.

    Google Scholar 

  13. Uhlmann, E., Greinerm B. and Breipohl, G. PNA/DNA chi-meras. In: P. Neilsen and M. Egholm (Eds.), Peptide Nucleic Acids. Norfolk: Horizon Scientific Press (1999) 51-70.

    Google Scholar 

  14. Stein, C.A. and Cohen, J.S. Phosphorothioate oligodeoxy-nucleotide analogues. In: J. Cohen (Ed.), Oligodeoxynuc-leotides: Antisense Inhibitors of Gene Expression. Boca Raton: CRC Press (1989) 97-117.

    Google Scholar 

  15. Demidov, V., Potaman, V.N., Frank-Kamenetskii, M.D., Buchardt, O., Egholm, M. and Nielsen, P.E. Stability of peptide nucleic acids in human serum and cellular extracts. Biochem. Pharmacol., 48 (1994) 1309-1313.

    Article  Google Scholar 

  16. Hudziak, R.M., Barofsky, E., Barofsky, D.F., Weller, D.L., Huang, S.B. and Weller, D.D. Resistance of Morpholino phosphorodiamidate oligomers to enzymatic degradation. Antisense Nucl. Acid Drug Dev., 6 (1996) 267-272.

    CAS  Google Scholar 

  17. Nutt, S.L., Bronchain, O.J., Hartley, K.O. and Amaya, E. Comparison of Morpholino based translational inhibi-tion during the development of Xenopus laevisand Xenopus tropicalis. Genesis, 30 (2001) 110-113.

    Article  CAS  PubMed  Google Scholar 

  18. Larsen, H.J. and Nielsen, P.E. Characterization of PNA-dsDNA strand displacement complexes. In: P. Neilsen and M. Egholm (Eds.), Peptide Nucleic Acids. Norfolk: Horizon Scientific Press (1999) 221-240.

    Google Scholar 

  19. Hanvey, J.C., Peffer, N.J., Bisi, J.E., Thomson, S.A., Ca-dilla, R., Josey, J.A., Ricca, D.J., Hassman, C.F., Bonham, M.A. and Au, K.G. et al.Antisense and antigene properties of peptide nucleic acids. Science, 258 (1992) 1481-1485.

    CAS  PubMed  Google Scholar 

  20. Selecting sequences for Morpholinos, targeting guidelines: http://www.gene-tools.com/Ordering/Ordering1/ body_ordering1.HTML

  21. Selecting sequences for PNAs, targeting guidelines: http://www.appliedbiosystems.com/support/seqguide.cfm

  22. Miller, P. Non-ionic antisense oligonucleotides: Oligo-nucleotide alkylphosphotriesters. In: J. Cohen (Ed.), Oli-godeoxynucleotides: Antisense Inhibitors of Gene Expres-sion. Boca Raton: CRC Press (1989) 82-85.

    Google Scholar 

  23. Miller, P. Non-ionic antisense oligonucleotides: Oligonuc-leotide methylphosphonates. In: J. Cohen (Ed.) Oligodeoxy-nucleotides: Antisense Inhibitors of Gene Expression. Boca Raton: CRC Press (1989) 85-92.

    Google Scholar 

  24. Stirchak, E., Summerton, J. and Weller, D. Uncharged ste-reoregular nucleic acid analogues. 1. Synthesis of a cytosine-containing oligomer with carbamate internucleoside link-ages. J. Org. Chem., 52 (1987) 4202-4206.

    Article  CAS  Google Scholar 

  25. Stirchak, E., Summerton, J. and Weller, D. Uncharged ste-reoregular nucleic acid analogues. 2. Morpholino nucleoside oligomers with carbamate internucleoside linkages. Nucl. Acids Res., 17 (1989) 6129-6141.

    CAS  PubMed  Google Scholar 

  26. Gildea, B.D., Casey, S., MacNeill, J., Perry-O'Keefe, H., Sørensen, D and Coull, J.M. Tetrah. Lett., 39 (1998) 7255.

    Article  CAS  Google Scholar 

  27. Kang, H., Chou, P., Johnson, C., Weller, D., Huang, S, and Summerton, J. Stacking interactions of ApA analogues with modified backbones. Biopolymers, 32 (1992) 1351-1363.

    Article  CAS  PubMed  Google Scholar 

  28. Genesis, 30 (2001) 3: Entire issue.

  29. Summerton, J., Stein, D., Huang, S., Matthews, P., Weller, D. and Partridge, M. Morpholino and Phosphorothioate an-tisense oligomers compared in cell-free and in-cell systems. Antis. Nucl. Acids Drug Dev., 7 (1997) 63-70.

    CAS  Google Scholar 

  30. Venter, J.C. et al.The sequence of the human genome. Science, 291 (2001) 1304-1351.

    Article  CAS  PubMed  Google Scholar 

  31. Stein, D., Foster, E., Huang, S.B., Weller, D. and Sum-merton, J. A specificity comparison of four antisense types: Morpholino, 2'-O-methyl RNA, DNA, and Phosphorothioate DNA. Antis. Nucl. Acids Drug Dev., 7 (1997) 151-157.

    CAS  Google Scholar 

  32. Summerton, J., Stein, D., Huang, S.B., Matthews, P., Weller, D. and Partridge, M. Morpholino and Phosphorothioate an-tisense oligomers compared in cell-free and in-cell systems. Antis. Nucl. Acids Drug Dev., 7 (1997) 63-70.

    CAS  Google Scholar 

  33. Akhtar, S., Basu, S., Wickstrom, E. and Juliano, R. In-teraction of antisense DNA oligonucleotide analogs with phospholipid membranes (liposomes). Nucl. Acids Res., 19 (1991) 5551-5559.

    CAS  PubMed  Google Scholar 

  34. Akhtar, S. and Juliano, R. Adsorption and efflux characterist-ics of modified oligodeoxynucleotides from liposomes. Proc. Am. Assoc. Cancer Res. 32 (1991) 333.

    Google Scholar 

  35. Neckers, L. Cellular internalization of oligodeoxynuc-leotides. In: S. Crooke and B. Lebleu B. (Eds.), Antisense Research and Applications. Boca Raton: CRC Press (1993) 451-460.

    Google Scholar 

  36. Simmons, C.G., Pitts, A.E., Mayfield, L.D., Shay, J.W. and Corey, D.R. Synthesis and membrane permeability of PNA-peptide conjugates. Bioorg. Med. Chem. Lett. 7 (1997) 3001.

    Article  CAS  Google Scholar 

  37. Pooga, M., Soomets, U., Hällbrink, M., Valkna, A., Saar, K., Rezaei, K., Kahl, U., Hao, J.X., Xu, X.J., Weisenfeld-Hallin, Z., Hökfelt, T., Bartfai, T. and Langel, Ñ. Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo. Nat. Biotechnol., 16 (1998) 857-861.

    Article  CAS  PubMed  Google Scholar 

  38. Tyler, B.M., McCormick, D.J., Hoshall, C.V., Douglas, C.L., Jansen, K, Lacy, B.W., Cusack, B. and Richelson, E. Specific gene blockade shows that peptide nucleic acids readily enter neuronal cells in vivo. FEBS Lett., 421 (1998) 280-284.

    Article  CAS  PubMed  Google Scholar 

  39. Pardridge, W.M., Boado, R.J. and Kang, Y.S. Vector-mediated delivery of a polyamide ('peptide') nucleic acid analogue through the blood-brain barrier in vivo. Proc. Natl. Acad. Sci, 92 (1995) 5592-5596.

    CAS  PubMed  Google Scholar 

  40. Aldrain-Herrada, G., Desarménien, M.G., Orcel, H., Boissin-Agasse, L., Méry, J., Brugidou, J. and Rabie, A. A peptide nucleic acid (PNA) is more rapidly internalized in cultured neurons when coupled to a retro-inverso delivery peptide. The antisense activity depresses the target mRNA and protein in magnocellular oxytocin neurons. Nucl. Acids Res., 26 (1998) 4910-4916.

    Google Scholar 

  41. Basu, S. and Wickstrom, E. Synthesis and characterization of a peptide nucleic acid conjugated to a D-peptide analog of insulin-like growth factor 1 for increased cellular uptake. Bioconj. Chem., 8 (1997) 481-488.

    CAS  Google Scholar 

  42. Good, L. and Nielsen, P.E. Antisense inhibition of gene expression in bacteria by PNA targeted to mRNA. Nat. Biotechnol., 16 (1998) 355-358.

    Article  CAS  PubMed  Google Scholar 

  43. Faruqi, A.F., Egholm, M. and Glazer, P.M. Peptide nucleic acid-targeted mutagenesis of a chromosomal gene in mouse cells. Proc. Natl. Acad. Sci. USA, 95 (1998) 1398-1403.

    Article  CAS  PubMed  Google Scholar 

  44. Partridge, M., Vincent, A., Matthews, P., Puma, J., Stein, D. and Summerton, J. A simple method for delivering Mor-pholino antisense oligos in to the cytoplasm of cells. Antis. Nucl. Acids Drug Dev., 6 (1996) 169-175.

    CAS  Google Scholar 

  45. Morcos, P.A. Gene switching: analyzing a broad range of mutations using steric block antisense oligonucleotides. Meth. Enzymol., 313 (1999) 174-189.

    Google Scholar 

  46. Morcos, P.A. Achieving efficient delivery of Morpholino oligos in cultured cells. Genesis, 30 (2001) 94-102.

  47. Monia, B., Johnston, J., Geiger, T., Muller, M. and Fabbro, D. Antitumor activity of a Phosphorothioate antisense oli-godeoxynucleotide targeted against C-raf kinase. Nat. Med., 2 (1996) 668-675.

    Article  CAS  PubMed  Google Scholar 

  48. Monia, B., Sasmor, H., Johnston, J., Freier, S., Lesnik, E., Muller, M., Geiger, T., Altmann, K., Moser, H. and Fabbro, D. Sequence-specific antitumor activity of a Phos-phorothioate oligodeoxyribonucleotide targeted to human C-raf kinase supports an antisense mechanism of action in vivo. Proc. Natl. Acad. Sci. USA, 93 (1996) 15481-15484.

    Article  CAS  PubMed  Google Scholar 

  49. Baker, B.F. and Monia, B.P. Novel mechanisms for antisense-mediated regulation of gene expression. Biochem. Biophys.Acta, 1489 (1999) 3-18.

    CAS  PubMed  Google Scholar 

  50. Quote from Stein, C. and Krieg, A., Non-antisense effects of oligodeoxynucleotides. In: C. Lichtenstein C. and Nellen, W. (Eds.) Antisense Technology. Oxford: IRL Press, 1997:260. '... non-antisense effects of PS oligos are also pointed out by a close examination of the oligo ISIS 2922, an 'antisense' oligo with remarkably potent antiviral effects against cytomegalovirus (CMV). ISIS 2922 is reported to have encouraging in vivoefficacy in early clinical trials against CMV retinitis. The sequence of this oligo is quite interesting because it has two atypical CpG motifs: there is a GCG at both the extreme 5' and 3' ends (79). Although not fully recognized at the time, published studies on ISIS 2922 demonstrate that its antiviral effect cannot be due to 'antisense'since internal mismatch control oligos lost very little antiviral activity despite a severe drop in the Tm. On the other hand, deletion of a single base from one of the CpG motifs caused a 40% drop in antiviral efficacy, and deletion of a single base from both of the CpG motifs abolished antiviral effect despite little change in the Tm for hybridization to the supposed mRNA target (79)'.

    Google Scholar 

  51. Kipshidze, N., Moses, J., Shankar, L.R. and Leon, M. Per-spectives on antisense therapy for the prevention of resten-osis. Curr. Opin. Mol. Ther., 3 (2001) 265-277.

    CAS  PubMed  Google Scholar 

  52. Kipshidze, N., Keane, E., Stein, D., Chawla, P., Skrinska, V., Shandar, L.R., Komorowski, R., Haudenschild, C., Leon, M., Keelan, M.H., Moses, J. and Iversen, P. Local delivery of antisense phosphorodiamidate morpholino oligomer; Resten-NG inhibits myointimal hyperplasia following balloon an-gioplasty. In: F. Navarro-Lopez (Ed.), XXIst Congress of the European Society of Cardiology. Italy: Monduzzi Editore (1999) 463-467.

    Google Scholar 

  53. Farrell, C., Bready, J., Saufman, S., Quian, Y. and Burgess, T. The uptake and distribution of Phosphorothioate oligonuc-leotides into vascular smooth muscle cells in vitroand in rabbit arteries. Antis. Res. Dev., 5 (1995) 175-183.

    CAS  Google Scholar 

  54. Kimmel, C.B. and Law, R.D. Cell lineage of zebrafish blastomeres. I. Cleavage pattern and cytoplasmic bridges between cells. Dev. Biol., 108 (1985) 78-85.

    CAS  PubMed  Google Scholar 

  55. Kimmel, C.B. and Law, R.D. Cell lineage of zebrafish blastomeres. II. Formation of the yolk syncytial layer. Dev. Biol., 108 (1985) 86-93.

    CAS  PubMed  Google Scholar 

  56. Stein, C. and Krieg, A. Non-antisense effects of oligodeoxy-nucleotides. In: C. Lichtenstein and W. Nellen (Eds.) Antis-ense Technology. Oxford: IRL Press (1997) 241-264.

    Google Scholar 

  57. Stein, C. Does antisense exist? Nat. Med., 1 (1995) 1119-1121.

    Article  CAS  PubMed  Google Scholar 

  58. Norton, J.C., Piatyszek, M.A., Wright, W.E., Shay, J.W. and Corey, D.R. Inhibition of human telomerase activity by peptide nucleic acids. Nat. Biotechnol., 14 (1996) 615-619.

    Article  CAS  PubMed  Google Scholar 

  59. Hamilton, S.E., Pitts, A.E., Katipally, R.R., Jia, X., Rutter, J.P., Davies, B.A., Shay, J.W., Wright, W.E. and Corey, D.R. Identification of determinants for inhibitor binding within the RNA active site of human telomerase using PNA scanning. Biochemistry, 36 (1997) 11873-11880.

    Article  CAS  PubMed  Google Scholar 

  60. Good, L., Awasthi, S.K., Dryselius, R., Larsson, O. and Nielson, P.E. Bactericidal antisense effects of peptide-PNA conjugates. Nat. Biotechnol., 19 (2001) 360-364.

    Article  CAS  PubMed  Google Scholar 

  61. Tyler, B.M., McCormick, D.J., Hoshall, C.V., Douglas, C.L., Jansen, K., Lacy, B.W., Cusack, B. and Richelson, E. Spe-cific gene blockade shows that peptide nucleic acids readily enter neuronal cells in vivo. FEBS Lett., 421 (1998) 280-284.

    Article  CAS  PubMed  Google Scholar 

  62. Rusckowski, M., Qu, T., Chang, F. and Hnatowich, D.J. Pretargeting using peptide nucleic acid. Cancer, 80 (1997) (12 suppl) 2699-2705.

    Article  CAS  PubMed  Google Scholar 

  63. Thisted, M., Just, T., Pluzek, K.J., Hyldig-Nielsen, J.J., Nielsen, K.V., Mollerup, T.A., Stender, H., Rasmussen, O.F., Adelhorst, K. and Godtfredsen, S.E. Application of peptide nucleic acid probes for in situhybridization. In: P. Nielsen and M. Egholm (Eds.) Peptide Nucleic Acids: Protocols and Applications. Wymondham: Horizon Scientific Press (1999) 99-118.

    Google Scholar 

  64. Matysiak, S., Würtz, S., Hauser, N.C., Gausepohl, H. and Hoheisel, J.D. PNA-arrays for nucleic acid detection. In: P. Nielsen and M. Egholm (Eds.), Peptide Nucleic Acids: Pro-tocols and Applications. Wymondham: Horizon Scientific Press (1999) 119-128.

    Google Scholar 

  65. Fiandaca, M.J., Hyldig-Nielsen, J.J. and Coull, J.M. PNA blocker probes enhance specificity in probe assays. In: P. Nielsen and M. Egholm (Eds.), Peptide Nucleic Acids: Pro-tocols and Applications. Wymondham: Horizon Scientific Press (1999) 129-142.

    Google Scholar 

  66. Griffin, T.J., Tang, W. and Smith, L.M. MALDI-TOF mass spectrometric detection of PNA hybrids for genetic ana-lysis. In: P. Nielsen and M. Egholm (Eds.), Peptide Nucleic Acids: Protocols and Applications. Wymondham: Horizon Scientific Press (1999) 143-154.

    Google Scholar 

  67. Wang, J. PNA biosensors for nucleic acid detection. In: P. Nielsen and M. Egholm (Eds.), Peptide Nucleic Acids: Pro-tocols and Applications. Wymondham: Horizon Scientific Press (1999) 155-161.

    Google Scholar 

  68. Lacerra, G., Sierakowska, H., Carestia, C., Fucharoen, S., Summerton, J., Weller, D. and Kole, R. Restoration of hemo-globin A synthesis in erythroid cells from peripheral blood of thalassemic patients. Proc. Natl. Acad. Sci. USA, 97 (2000) 9591-9596.

    Article  CAS  PubMed  Google Scholar 

  69. Deng, J., Hua, K., Lesser, S.S. and Harp, J.B. Activation of signal transducer and activator of transcription-3 during proliferative phases of 3T3-L1 adipogenesis. Endocrinology, 141 (2000) 2370-2376.

    Article  CAS  PubMed  Google Scholar 

  70. Lawn, R.M., Wade, D.P., Garvin, M.R., Wang, X., Schwartz, K., Porter, J.G., Seilhamer, J.J., Vaughan, A.M. and Oram, J.F. The Tangier disease gene product ABC1 controls the cel-lular apolipoprotein-mediated lipid removal pathway. J. Clin. Invest., 104 (1999) R25-R31.

    CAS  PubMed  Google Scholar 

  71. Giles, R.V., Spiller, D.G., Clark, R.E. and Tidd, D.M. Antis-ense morpholino oligonucleotide analog induces missplicing of c-myc mRNA. Antis. Nucl. Acids Drug Dev., (Apr)9(2) (1999) 213-20.

    Google Scholar 

  72. Heasman, J., Kofron, M. and Wylie, C. Beta-catenin signal-ing activity dissected in the early Xenopusembryo: a novel antisense approach. Devel. Biol., 222 (2000) 124-134.

    Article  CAS  Google Scholar 

  73. Nasevicius, A. and Ekker, S.C. Effective targeted gene 'knockdown' in zebrafish. Nat. Genetics, 26 (2000) 216-220.

    CAS  Google Scholar 

  74. Howard, E.W., Newman, L.A., Oleksyn, D.W., Angerer, R.C. and Angerer, L.M. SpKrl: a direct target of (beta)-catenin regulation required for endoderm differentiation in sea urchin embryos. Development, 128 (2001) 365-375.

    CAS  PubMed  Google Scholar 

  75. Kos, R., Reedy, M.V., Johnson, R.L. and Erickson, C.A. The winged-helix transcription factor FoxD3 is important for es-tablishing the neural crest lineage and repressing melanogen-esis in avian embryos. Development, 128 (2001) 1467-1479.

    CAS  PubMed  Google Scholar 

  76. Draper, B.W., Morcos, P.A. and Kimmel, C.B. Inhibition of zebrafish fgf8pre-mRNA splicing with Morpholino oligos: a quantifiable method for gene knockdown. Genesis, 30 (2001) 154-156.

    Article  CAS  PubMed  Google Scholar 

  77. Elbeik, T. et al.Quantitative and cost comparison of ultra-sensitive human immunodeficiency virus type 1 RNA viral load assays. J. Clin. Micro., 39 (2000) 1113-1120

    Google Scholar 

  78. Summerton, J.E., Weller, D.D. and Wages, J.M. Reagent and method for isolation and detection of selected nucleic acid sequences. US Patent; (2000), 6,060,246.

  79. Tyler, B.M., McCormick, D.J., Hoshall, C.V., Douglas, C.L., Jansen, K., Lacy, B.W., Cusack, B. and Richelson, E. Spe-cific gene blockade shows that peptide nucleic acids readily enter neuronal cells in vivo. FEBS Lett. 421 (1998) 280-284.

    Article  CAS  PubMed  Google Scholar 

  80. Arora, V. and Iversen, P. Redirection of drug metabolism using antisense technology. Curr. Opin. Mol. Ther., 3 (2001) 249-257.

    CAS  PubMed  Google Scholar 

  81. Brand, R.M. and Iversen, P.L. Transdermal delivery of an-tisense compounds. Adv. Drug Develop. Rev., 44 (2000) 51-58.

    CAS  Google Scholar 

  82. Aurora, V. and Iversen, P.L. Antisense oligonucleotides tar-geted to the p53 gene modulate rat liver regeneration. Drug. Metab. Disp., 28 (2000) 131-138.

    Google Scholar 

  83. Qin, G., Taylor, M., Ning, Y.Y., Iversen, P. and Kobzik, L. In vivoevaluation of a morpholino antisense oligomer directed against TNF. Antis. Nucl. Acids Drug Develop., 10 (2000) 11-16.

    CAS  Google Scholar 

  84. Stein, C.A. and Cohen, J.S. Phosphorothioate oligodeoxy-nucleotide analogues. In: J. Cohen (Ed.), Oligodeoxynuc-leotides: Antisense Inhibitors of Gene Expression. Boca Raton: CRC Press (1989) 97-117.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. President, Gene Tools, Inc. One Summerton Way, Philomath, OR, 97370, U.S.A.;

    James E. Summerton

Authors
  1. James E. Summerton
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Summerton, J.E. Morpholinos and PNAs compared. Int J Pept Res Ther 10, 215–236 (2003). https://doi.org/10.1007/s10989-004-4913-y

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10989-004-4913-y

Keywords

Search

Navigation