Applications of peptide nucleic acids

Current Opinion in Biotechnology

Volumn 10, Issue 1, 1999, Pages 71-75

  Nielsen, Peter E ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENTARY DNA; PEPTIDE NUCLEIC ACID;

CHEMICAL STRUCTURE; DRUG TARGETING; ESCHERICHIA COLI; GENE THERAPY; NERVE CELL; NONHUMAN; NUCLEIC ACID HYBRIDIZATION; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN STRUCTURE; RAT; REVIEW;

ESCHERICHIA COLI; EUKARYOTA;

EID: 0032925881     PISSN: 09581669     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0958-1669(99)80013-5     Document Type: Article

References (47)

1. Nielsen PE, Egholm M, Berg RH, Buchardt O Sequence selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science. 254:1991;1497-1500.
2. Egholm M, Buchardt O, Christensen L, Behrens C, Freier SM, Driver DA, Berg RH, Kim SK, Nordén B, Nielsen PE PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen bonding rules. Nature. 365:1993;556-568.
3. Wittung P, Nielsen PE, Buchardt O, Egholm M, Nordén B DNA-like double helix formed by peptide nucleic acid. Nature. 368:1994;561-563.
4. Hyrup B, Nielsen PE Peptide nucleic acids (PNA). Synthesis, properties and potential applications. Bioorg Biomed Chem. 4:1996;5-23.
5. Good L, Nielsen PE Progress in developing PNA as a gene-targeted drug. Antisense Nucleic Acid Drug Dev. 7:1997;431-437.
6. Cherny DY, Belotserkovskii BP, Frank-Kamenetskii MD, Egholm M, Buchardt O, Berg RH, Nielsen PE DNA unwinding upon strand displacement of binding of PNA to double stranded DNA. Proc Natl Acad Sci USA. 90:1993;1667-1670.
7. 2/DNA triplex structure upon binding of PNA to dsDNA by strand displacement. J Mol Recognit. 7:1994;165-170.
8. Bonham MA, Brown S, Boyd AL, Brown PH, Bruckenstein DA, Hanvey JC, Thomson SA, Pipe A, Hassman F, Bisi JEet al. An assessment of the antisense properties of RNAse H-competent and steric-blocking oligomers. Nucleic Acids Res. 23:1995;1197-1203.
9. Simmons CG, Pitts AE, Mayfield LD, Shay JW, Corey DR Synthesis and membrane permeability of PNA-peptide conjugates. Bioorg Med Chem Lett. 7:1997;3001-3006.
10. ••] are the first reports of (antisense) effects of PNA in animal systems; however, it is pertinent to establish whether such effects are peculiar to the nervous system.
11. ••].
12. Good L, Nielsen PE Antisense inhibition of gene expression in bacteria by PNA targeted to mRNA. Nat Biotechnol. 16:1998;355-358. 15-mer PNAs were targeted to the AUG initiation codon of the β-galactosidase and β-lactamase genes in E. coli. Gene specific, dose dependent antisense downregulation of these genes is demonstrated in the more permeable strain AS19 (effects were also seen in wild-type K12). Furthermore, downregulation of the β-lactamase gene resensitized the bacteria to ampicillin by six orders of magnitude. These results open the possibilities for developing 'genetic antibiotics' and provide a means for performing target validation and functional genomics studies by the antisense technique in bacteria.
13. Good L, Nielsen PE Inhibition of translation and bacterial growth by peptide nucleic acid targeted to ribosomal RNA. Proc Natl Acad Sci USA. 95:1998;2073-2076. PNAs were designed to bind to ribosomal RNA of E. coli. Of ten PNAs tested, two inhibited in vitro translation and bacterial growth of AS19 at low micomolar concentrations. These were triplex forming bis-PNAs targeting homopurine sequences in the α-sarcin loop and in the peptidyl transferase center. These results introduce ribosomal RNA as a target for (microbial) antisense drugs.
14. Nielsen PE, Egholm M, Buchardt O Sequence specific transcription arrest by PNA bound to the template strand. Gene. 149:1994;139-145.
15. Vickers TA, Griffith MC, Ramasamy K, Risen LM, Freier SM Inhibition of NF-kappa B specific transcriptional activation by PNA strand invasion. Nucleic Acids Res. 23:1995;3003-3008.
16. Kurakin A, Larsen HJ, Nielsen PE Cooperative strand displacement by peptide nucleic acid (PNA). Chem Biol. 5:1998;81-89.
17. Larsen HJ, Nielsen PE Transcription-mediated binding of peptide nucleic acid (PNA) to double-stranded DNA: sequence-specific suicide transcription. Nucleic Acids Res. 24:1996;458-463.
18. Bentin T, Nielsen PE Enhanced peptide nucleic acid binding to supercoiled DNA: possible implications for DNA 'breathing' dynamics. Biochemistry. 35:1996;8863-8869.
19. Faruqi AF, Egholm M, Glazer PM Peptide nucleic acid-targeted mutagenesis of a chromosomal gene in mouse cells. Proc Natl Acad Sci USA. 95:1998;1398-1403.
20. Boffa LC, Carpaneto EM, Mariani MR, Louissaint M, Allfrey VG Contrasting effects of PNA invasion of the chimeric DMMYC gene on transcription of its myc and PVT domains. Oncol Res. 9:1997;41-51.
21. Rusckowski M, Qu T, Chang F, Hnatowich DJ Pretargeting using peptide nucleic acid. Cancer. 80:1997;2699-2705. This paper utilizes PNAs as general recognition reagents with an overwhelming number of code combinations. Further applications along these lines should be interesting to pursue.
22. Jensen KK, Orum H, Nielsen PE, Norden B Kinetics for hybridization of peptide nucleic acids (PNA) with DNA and RNA studied with the BIAcore technique. Biochemistry. 36:1997;5072-5077.
23. Weiler J, Gausepohl H, Hauser N, Jensen ON, Hoheisel JD Hybridisation based DNA screening on peptide nucleic acid (PNA) oligomer arrays. Nucleic Acids Res. 25:1997;2792-2799. A technique to synthesise PNA arrays on membranes is presented. The technique still requires further validation, but could be very useful in diagnostics and gene expression analyses.
24. Wang J, Palecek E, Nielsen PE, Rivas G, Cai X, Shiraishi H, Dontha N, Luo D, Farias MA Peptide nucleic acid probes for sequence-specific DNA biosensors. J Am Chem Soc. 118:1996;7667-7670.
25. Wang J, Nielsen PE, Jiang M, Cai X, Fernandes JR, Grant DH, Ozsoz M, Beglieter A, Mowat M Mismatch-sensitive hybridization detection by peptide nucleic acids immobilized on a quartz crystal microbalance. Anal Chem. 69:1997;5200-5202.
26. Arlinghaus HF, Kwoka MN, Jacobson KB Analysis of biosensor chips for identification of nucleic acids. Anal Chem. 69:1997;3747-3753. Biosensors are extremely interesting tools in diagnostics and may also be developed for genetic diagnostics. In this approach, the difference in PNA and DNA chemistry (specifically the lack of phosphorous in PNA) is exploited for detection of the hybridized DNA.
27. Griffin TJ, Tang W, Smith LM Genetic analysis by peptide nucleic acid affinity MALDI-TOF mass spectrometry. Nat Biotechnol. 15:1997;1368-1372. Mass spectrometry is gaining increased recognition as an extremely important method for detection and analysis of (large) biomolecules. This paper demonstrates that multiplex genetic analysis can be performed using PNA hybridization to immobilized DNA samples. The analysis is based on MALDI-TOF analyses of the hybridized PNA (released on the MS grid), and by simply engineering slightly different masses into the various gene-specific PNAs the mass of the PNA, identifies the gene. This methodology may become very important in future diagnostics.
28. ••], demonstrates the power of mass spectrometric detection of PNA hybridization. These authors, however, did not employ mass tags, but rather relied on the PNA mass differences originating from sequence/length variations.
29. Ross PL, Lee K, Belgrader P Discrimination of single-nucleotide polymorphisms in human DNA using peptide nucleic acid probes detected by MALDI-TOF mass spectrometry. Anal Chem. 69:1997;4197-4202.
30. Lansdorp PM, Verwoerd NP, Rijke van de FM, Dragowska V, Little M-T, Dirks RW, Raap AK, Tanke HJ Heterogeneity in telomere length of human chromosomes. Hum Mol Genet. 5:1996;685-691.
31. Thisted M, Just T, Pluzek K-J, Petersen KH, Hyldig-Nielsen JJ, Godtfredsen SE Detection of immunoglobulin kappa light chain mRNA in paraffin sections by in situ hybridization using peptide nucleic acid probes. Cell VISION. 3:1996;358-363.
32. Taneja KL Localization of trinucleotide repeat sequences in myotonic dystrophy cells using a single fluorochrome-labeled PNA probe. Biotechniques. 24:1998;472-476.
33. Rufer N, Dragowska W, Thornbury G, Roosnek E, Lansdorp PM Telomere length dynamics in human lymphocyte subpopulations measure by flow cytometry. Nat Biotechnol. 16:1998;743-747.
34. Boei JJWA, Vermeulen S, Fomina J, Natarajan AT Detection of incomplete exchanges and interstitial fragments in X-irradiated human lymphocytes using a telomeric PNA probe. J Radiat Biol. 73:1998;599-603.
35. Pauw de ESD, Verwoerd NP, Duinkerken N, Willemze R, Raap AK, Fibbe WE, Tanke HJ Assessment of telomere length in hematopoietic interphase cells using in situ hybridization and digital fluorescence microscopy. Cytometry. 32:1998;163-169.
36. Hultdin M, Grönlund E, Norrback KE, Eriksson-Lindström E, Just T, Roos G Telomere analysis by fluorescence in situ hybridisation and flow cytometry. Nucleic Acids Res. 26:1998;3651-3656.
37. Ørum H, Nielsen PE, Egholm M, Berg RH, Buchardt O, Stanley C Single base pair mutation analysis by PNA directed PCR clamping. Nucleic Acids Res. 21:1993;5332-5336.
38. Rhodes CH, Honsinger C, Porter DM, Sorenson GD Analysis of the allele-specific PCR method for the detection of neoplastic disease. Diagn Mol Pathol. 6:1997;49-57. Although this application of the PCR clamping technique was anticipated, this is the first demonstration that it is a useful tool to help silence a large signal from normal cells when searching for cancer cells. In this case, the cancer gene was detected on a background of 300,000-fold normal genes. This should have major implications in cancer diagnostics.
39. Behn M, Schuermann M Simple and reliable factor V genotyping by PNA-mediated PCR clamping. Thromb Haemost. 79:1998;773-777.
40. Mrozikiewicz PM, Cascorbi I, Brockmoller J, Roots I CYP1A1 mutations 4887A, 4889G, 5639C and 6235C in the Polish population and their allelic linkage, determined by peptide nucleic acid-mediated PCR clamping. Pharmacogenetics. 7:1997;303-307. Exemplifies the broad utility of PCR clamping in genetic screening. Specifically, it demonstrates how this technology is used in genetic diagnostic population screening.
41. Aynacioglu AS, Cascorbi I, Mrozikiewicz PM, Roots I High frequency of CYP1A1 mutations in a Turkish population. Arch Toxicol. 72:1998;215-218.
42. Ortiz E, Estrada G, Lizardi PM PNA molecular beacons for rapid detection of PCR amplicons. Mol Cell Probes. 12:1998;219-226.
43. Ørum H, Jørgensen M, Koch T, Nielsen PE, Larsson C, Stanley C Sequence specific purification of nucleic acids by PNA controlled hybrid selection. Biotechniques. 19:1995;472-480.
44. Seeger C, Batz HG, Orum H PNA-mediated purification of PCR amplifiable human genomic DNA from whole blood. Biotechniques. 23:1997;512-517. Sample preparation and purification is now being realized as a (or maybe the) most critical step in genetic diagnostics. This paper demonstrates a very simple, elegant and general method for DNA purification (from blood) for PCR analysis.
45. Bukanov NO, Demidov VV, Nielsen PE, Frank-Kamenetskii MD PD loop: a complex of duplex DNA with an oligonucleotide. Proc Natl Acad Sci USA. 95:1998;5516-5520. A method based on oligonucleotide capture of double stranded DNA has been developed. By opening the double stranded DNA with two bis-PNAs whose binding sites flank the capture site, efficient and extremely sequence-specific capture is achieved. The method requires that for the DNA fragment to be caught two closely positioned (<10 basepairs apart) homopurine tracts each at least seven bases can be found in the DNA fragment.
46. Griffin TJ, Smith LM An approach to predicting the stabilities of peptide nucleic acid: DNA duplexes. Anal Biochem. 15:1998;56-63.
47. Giesen U, Kleider W, Berding C, Geiger A, Ørum H, Nielsen PE: A formula for thermal stability (Tm) prediction of PNA/DNA duplexes. Nucleic Acids Res 1998, in press. An empirical method for calculation of the thermal stability (Tm) of PNA-DNA duplexes (6-20bp) has been derived using the Tm calculated by the nearest neighbour model for the corresponding DNA-DNA duplex and using linear correction factors. The model is based on over 300 measured Tms, and was validated on an independent data set. More than 95% of the determinations fell within 5°C of the measured Tm.