Advertisement

Peptide Nucleic Acids

Cellular Delivery and Recognition of DNA and RNA Targets
  • David R. Corey
Chapter
  • 643 Downloads
Part of the Medical Intelligence Unit book series (MIUN)

Abstract

Peptide nucleic acids (PNAs) can be conveniently delivered into cells in complex with DNA and cationic lipid. This advance enables researchers to test the hypothesis that PNAs offer advantages for recognition of DNA or RNA targets within cells. In this review, I describe the intracellular delivery of PNAs as DNA-PNA-cationic lipid complexes and discuss recognition of three classes of nucleic acid target: duplex DNA, single-stranded mRNA, and the ribonucleoprotein telomerase. These targets differ dramatically in their potential for base-paired structure, offering distinct challenges for hybridization by PNAs. It is apparent that PNAs can exert sequence-specific effects within cells, and their full potential has only begun to be explored.

Keywords

Peptide Nucleic Acid Cationic Lipid Intracellular Delivery Nucleic Acid Target Cellular Delivery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Nielson PE, Egholm M, Berg RH et al. Sequence-selective recognition of double stranded DNA by a thymine-substituted polyamide. Science 1991; 254:1497–1500.CrossRefGoogle Scholar
  2. 2.
    Egholm M, Buchardt O, Christensen L et al. PNA hybridizes to complementary oligonucleotides obeying the watson-crick hydrogen bonding rules. Nature 1993; 365:566–568.PubMedCrossRefGoogle Scholar
  3. 3.
    Freier SM, Altmann K-H. The ups and downs of nucleic acid duplex stability: Structurestability studies on chemically-modified DNA:RNA duplexes. Nucl Acids Res 1997; 25:4429–4443.PubMedCrossRefGoogle Scholar
  4. 4.
    Hamilton SE, Iyer M, Norton JC et al. Specific and nonspecific inhibition of RNA synthesis by DNA, PNA and phosphorothioate promoter analog duplexes. Bioorg Med Chem Lett 1996; 6:2897–2900.CrossRefGoogle Scholar
  5. 5.
    Demidov VV, Potaman VN, Frank-Kamenetskii MD et al. Stability of peptide nucleic acids in human serum and cellular extracts. Biochem Pharmacol 1994; 48:1310–1313.PubMedCrossRefGoogle Scholar
  6. 6.
    Demidov VV, Frank-Kamenetskii MD, Egholm M et al. Sequence selective cleavage of double stranded DNA cleavage by peptide nucleic acid (PNA) targeting using S1 nuclease. Nucl Acids Res 1993; 21:2103–2107.PubMedCrossRefGoogle Scholar
  7. 7.
    Demidov VV, Cherny DI, Kurakin AV et al. Electron microscopy mapping of oligopurine tracts in duplex DNA by peptide nucleic acid targeting. Nucl Acids Res 1994; 22:5218–5222.PubMedCrossRefGoogle Scholar
  8. 8.
    Demidov VV, Belotserkovaski BP, Frank-Kamenetskii M et al. DNA unwinding upon strand displacement of a thymine substituted polyamide to double-stranded DNA. Proc Nat Acad Sci USA 1993; 90:1667–1670.CrossRefGoogle Scholar
  9. 9.
    Bukanov NO, Demidov VV, Nielson PE et al. PD loop: A complex of duplex DNA with an oligonucleotide. Proc Nat Acad Sci USA 1998; 95:5516–5520.PubMedCrossRefGoogle Scholar
  10. 10.
    Lohse J, Dahl O, Nielsen PE. Double duplex invasion by peptide nucleic acid: A general principle for sequence specific targeting of double-stranded. DNA 1999; 96:11804–11808.Google Scholar
  11. 11.
    Footer M, Egholm M, Kron S et al. Biochemical evidence that a D-loop is part of four stranded PNA-DNA bundle. Biochemistry 1996; 35:10673–10679.PubMedCrossRefGoogle Scholar
  12. 12.
    Smulevitch SV, Simmons CG, Norton JC et al. Enhanced strand invasion by oligonucleotides through manipulation of backbone charge. Nature Biotech 1996; 14:1700–1704.CrossRefGoogle Scholar
  13. 13.
    Norton JC, Waggenspack JJ, Varnum E et al. Targeting peptide nucleic acid protein conjugates to structural features within duplex DNA.. Bioorg Med Chem 1995; 3:437–445.PubMedCrossRefGoogle Scholar
  14. 14.
    Ishihara T, Corey DR. Rules for strand invasion by chemically modified oligonucleotides. J Am Chem Soc 1999; 121:2012–2020.CrossRefGoogle Scholar
  15. 15.
    Zhang X, Ishihara T, Corey DR. Strand invasion by mixed base PNAs and PNA-peptide chimera. Nucl Acids Res 2000; 28:3332–3338.PubMedCrossRefGoogle Scholar
  16. 16.
    Hamilton SE, Pitts AE, Katipally RR et al. Identification of determinants for inhibitor binding within the RNA active site of human telomerase using PNA scanning. Biochemistry 1997; 36:11873–11880.PubMedCrossRefGoogle Scholar
  17. 17.
    Griffith MC, Risen LM, Greig MJ et al. Single and bis peptide nucleic acids as triplexing agents: Binding and stoichiometry. J Am Chem Soc 1995; 117:831–832.CrossRefGoogle Scholar
  18. 18.
    Zelphati O, Liang X, Nguyen C et al. PNA-dependent gene chemistry: Stable coupling of peptides and oligonucleotides to plasmid DNA. Biotechniques 2000; 28:304–315.PubMedGoogle Scholar
  19. 19.
    Lindgren M, Hallbrink M, Prochiantz A et al. Cell penetrating peptides. Trends in Pharm Sci 2000; 21:99–103.CrossRefGoogle Scholar
  20. 20.
    Zhang X, Simmons CG, Corey DR. Synthesis and intracellular delivery of lactose-labeled PNAs. Bioorg Med Chem Lett 2001; 11:1269–1272.PubMedCrossRefGoogle Scholar
  21. 21.
    Simmons CG, Pitts AE, Mayfield LD et al. Synthesis and membrane permeability of PNA-peptide conjugates. Bioorg Med Chem Lett 1997; 7:3001–3007.CrossRefGoogle Scholar
  22. 22.
    Pooga M, Soomets U, Hallbrink M et al. Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo. Nat Biotech 1998; 16:857–861.CrossRefGoogle Scholar
  23. 23.
    Hamilton SE, Simmons CG, Kathriya I et al. Cellular delivery of peptide nucleic acids and inhibition of human telomerase. Chem Biol 1999; 6:343–351.PubMedCrossRefGoogle Scholar
  24. 24.
    Braasch DA, Corey DR. Synthesis, analysis, purfication, and intracellular delivery of peptide nucleic acids. Methods 2001; 23:97–107.PubMedCrossRefGoogle Scholar
  25. 25.
    Doyle DF, Braasch DA, Simmons CG et al. Intracellular delivery and inhibition of gene expression by peptide nucleic acids. Biochemistry 2001; 40:53–64.PubMedCrossRefGoogle Scholar
  26. 26.
    Herbert BS, Pitts AE, Baker SI et al. Inhibition of telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc Nat Acad Sci 1999; 96:14726–14281.CrossRefGoogle Scholar
  27. 27.
    Shammas MA, Simmons CG, Corey DDR et al. Telomerase inhibition by peptide nucleic acids reverses “Immortality” of transformed cells. Oncogene 1999; 18:6191–6200.PubMedCrossRefGoogle Scholar

Copyright information

© Eurekah.com and Kluwer Academic / Plenum Publishers 2006

Authors and Affiliations

  • David R. Corey
    • 1
  1. 1.Departments of Pharmacology and BiochemistryUniversity of Texas Southwestern Medical CenterDallasUSA

Personalised recommendations