Peptide nucleic acids: A review on recent patents and technology transfer

Expert Opinion on Therapeutic Patents

Volumn 24, Issue 3, 2014, Pages 267-294

  Gambari, Roberto ^a  

^a UNIVERSITY OF FERRARA   (Italy)

Author keywords

Antisense PNAs; Delivery; Gene therapy; Molecular diagnosis; Peptide nucleic acids; PNA DNA chimeras; Technology transfer

Indexed keywords

MICRORNA; MITOCHONDRIAL DNA; PEPTIDE NUCLEIC ACID; TRANSCRIPTION FACTOR;

BACTERIAL GROWTH; BACTERIAL VIABILITY; BIOLOGICAL ACTIVITY; BIOLOGY; CLINICAL TRIAL (TOPIC); DNA RNA HYBRIDIZATION; DRUG EFFICACY; DRUG SAFETY; GENE EXPRESSION; GENE TARGETING; GENE THERAPY; HUMAN; IN VIVO GENE TRANSFER; MOLECULAR DIAGNOSIS; NONVIRAL GENE THERAPY; NUCLEIC ACID PROBE; POINT MUTATION; POLYMERASE CHAIN REACTION; REVIEW; SOLUBILITY; TARGET CELL; TECHNOLOGY; TRIPLE HELIX;

ANIMALS; BINDING SITES; GENE EXPRESSION REGULATION; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; HUMANS; MOLECULAR DIAGNOSTIC TECHNIQUES; MOLECULAR IMAGING; NUCLEIC ACID CONFORMATION; PATENTS AS TOPIC; PEPTIDE NUCLEIC ACIDS; PROMOTER REGIONS, GENETIC; PROTEIN CONFORMATION; TECHNOLOGY TRANSFER; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 84896719167     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2014.863874     Document Type: Review

References (227)

1. Deshpande A, White PS. Multiplexed nucleic acid-based assays for molecular diagnostics of human disease. Expert Rev Mol Diagn 2012;12:645-59
2. Pellestor F, Paulasova P. The peptide nucleic acids, efficient tools for molecular diagnosis. Int J Mol Med 2004;13:521-5
3. Prabhu P, Patravale V. The upcoming field of theranostic nanomedicine: An overview. J Biomed Nanotechnol 2012;8:859-82
4. Mokhir AA, Kraemer R. Conjugates of PNA with naphthalene diimide derivatives having a broad range of DNA affinities. Bioconjug Chem 2003;14:877-83
5. Majumder P, Gomes KN, Ulrich H. Aptamers: From bench side research towards patented molecules with therapeutic applications. Expert Opin Ther Pat 2009;19:1603-13. A review outlining the steps to be followed to developing patents based on aptameric molecules exhibiting in vitro biological properties.
6. Abes S, Ivanova GD, Abes R, et al. Peptide-based delivery of steric-block PNA oligonucleotides. Methods Mol Biol 2009;480:85-99. A key paper on the delivery of PNAs.
7. Lukin M, Zaliznyak T, Johnson F, De Los Santos CR. Incorporation of 3-aminobenzanthrone into 2-deoxyoligonucleotides and its impact on duplex stability. J Nucleic Acids 2011;2011:521035
8. Schneider PN, Olthoff JT, Matthews AJ, Houston DW. Use of fully modified 2-O-methyl antisense oligos for loss-of-function studies in vertebrate embryos. Genesis 2011;49:117-23
9. Oberhauser B, Wagner E. Effective incorporation of 2-O- methyloligoribonucleotides into liposomes and enhanced cell association through modification with thiocholesterol. Nucleic Acids Res 1992;20:533-8
10. Nawrot B, Sipa K. Chemical and structural diversity of siRNA molecules. Curr Top Med Chem 2006;6:913-25
11. Fabani MM, Gait MJ. miR-122 targeting with LNA/2-Omethyl oligonucleotide mixmers, peptide nucleic acids (PNA), and PNA-peptide conjugates. RNA 2008;14:336-46
12. Polak M, Manoharan M, Inamati GB, Plavec J. Tuning of conformational preorganization in model 2,5-and 3,5-linked oligonucleotides by 3-and 2-O-methoxyethyl modification. Nucleic Acids Res 2003;31:2066-76
13. Selvakumar LS, Thakur MS. Nano RNA aptamer wire for analysis of vitamin B12. Anal Biochem 2012;427:151-7
14. Liu CH, Lu DD, Deng XX, et al. The analysis of major impurities of lipophilicconjugated phosphorothioate oligonucleotides by ion-pair reversedphase HPLC combined with MALDI-TOF-MS. Anal Bioanal Chem 2012;403:1333-42
15. Guga P, Koziokiewicz M. Phosphorothioate nucleotides and oligonucleotides-recent progress in synthesis and application. Chem Biodivers 2011;8:1642-81
16. Nielsen PE, Egholm M, Berg RH, Buchardt O. Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 1991;254:1497-500.. The key original paper with the first description of PNAs.
17. Demidov VV, Frank-Kamenetskii MD. Sequence-specific targeting of duplex DNA by peptide nucleic acids via triplex strand invasion. Methods 2001;23:108-22
18. Guo S, Du D, Tang L, et al. PNA-assembled graphene oxide for sensitive and selective detection of DNA. Analyst 2013;138:3216-20
19. Egholm M, Buchardt O, Christensen L, et al. PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules. Nature 1993;365:566-8.. A key paper showing the ability of PNAs in experiments based on hybridization.
20. Marin VL, Roy S, Armitage BA. Recent advances in the development of peptide nucleic acid as a gene-targeted drug. Expert Opin Biol Ther 2004;4:337-48
21. McNeer NA, Schleifman EB, Cuthbert A, et al. Systemic delivery of triplex-forming PNA and donor DNA by nanoparticles mediates site-specific genome editing of human hematopoietic cells in vivo. Gene Ther 2013;20:658-69
22. Shiraishi T, Nielsen PE. Peptide nucleic acid (PNA) cell penetrating peptide (CPP) conjugates as carriers for cellular delivery of antisense oligomers. Artif DNA PNA XNA 2011;2:90-9
23. Borgatti M, Breda L, Cortesi R, et al. Cationic liposomes as delivery systems for double-stranded PNA-DNA chimeras exhibiting decoy activity against NFkappaB transcription factors. Biochem Pharmacol 2002;64:609-16.. An important paper on the delivery of PNA-DNA chimeras.
24. Available from: Http://www.freepatentsonline.com/
25. Available from: Http://www.google.patents.com/
26. Available from: Http://worldwide. espacenet.com/
27. Ahn SY, Choi H, Choi H, et al. PNA monomer and precursor. US7125994; 2006
28. Brolin C, Shiraishi T. Antisense mediated exon skipping therapy for duchenne muscular dystrophy (DMD). Artif DNA PNA XNA 2011;2:6-15
29. Parkash B, Ranjan A, Tiwari V, et al. Inhibition of 5-UTR RNA conformational switching in HIV-1 using antisense PNAs. PLoS One 2012;7:e49310
30. Tonelli R, McIntyre A, Camerin C, et al. Antitumor activity of sustained N-myc reduction in rhabdomyosarcomas and transcriptional block by antigene therapy. Clin Cancer Res 2012;18:796-807
31. Malchère C, Verheijen J, Van der Laan S, et al. A short phosphodiester window is sufficient to direct RNase HdependeRNA cleavage by antisense peptide nucleic acid. Antisense Nucleic Acid Drug Dev 2000;10:463-8.. An important paper demonstrating the requirement of PNA-based molecules to activate RNAseH-depended cleavage.
32. Kilk K, Elmquist A, Saar K, et al. Targeting of antisense PNA oligomers to human galanin receptor type 1 mRNA. Neuropeptides 2004;38:316-24
33. Shiraishi T, Nielsen PE. Down-regulation of MDM2 and activation of p53 in human cancer cells by antisense 9-aminoacridine-PNA (peptide nucleic acid) conjugates. Nucleic Acids Res 2004;32:4893-902
34. Dragulescu-Andrasi A, Rapireddy S, He G, et al. Cell-permeable peptide nucleic acid designed to bind to the 5-untranslated region of E-cadherin transcript induces potent and sequencespecific antisense effects. J Am Chem Soc 2006;128:16104-12
35. Pandey VN, Upadhyay A, Chaubey B. Prospects for antisense peptide nucleic acid (PNA) therapies for HIV. Expert Opin Biol Ther 2009;9:975-89
36. Tonelli R, Pession A, Fronza R, et al. Method for selective inhibition of human n-myc gene in n-myc expressing tumors through antisense and antigen peptidonucleic acids (PNA). US2007020632; 2007. An important patent on applications of PNAs as anti-tumor agents.
37. Wickstrom E, Thakur ML. Antisense compounds and methods for diagnostic imaging. US20110123988; 2011
38. Ivanova GD, Arzumanov A, Abes R, et al. Improved cell-penetrating peptide-PNA conjugates for splicing redirection in HeLa cells and exon skipping in mdx mouse muscle. Nucleic Acids Res 2008;36:6418-28
39. Saleh AF, Arzumanov A, Abes R, et al. Synthesis and splice-redirecting activity of branched, arginine-rich peptide dendrimer conjugates of peptide nucleic acid oligonucleotides. Bioconjug Chem 2010;21:1902-11
40. Yin H, Betts C, Saleh AF, et al. Optimization of peptide nucleic acid antisense oligonucleotides for local and systemic dystrophin splice correction in the mdx mouse. Mol Ther 2010;18:819-27.. A key paper showing the use of PNAs for splice correction.
41. Saleh AF, Arzumanov AA, Gait MJ. Overview of alternative oligonucleotide chemistries for exon skipping. Methods Mol Biol 2012;867:365-78
42. Pankratova S, Nielsen BN, Shiraishi T, Nielsen PE. PNA-mediated modulation and redirection of Her-2 premRNA splicing: Specific skipping of erbB-2 exon 19 coding for the ATP catalytic domain. Int J Oncol 2010;36:29-38
43. Wood M, Yin H-F. Treatment of muscular dystrophy using peptide nucleic acids (PNA). WO2009101399; 2009. A key patent application on a therapeutic field in which other DNAbased molecules have shown very interesting activity.
44. Oh SY, Ju Y, Kim S, et al.A-based antisense oligonucleotides for micrornas inhibition in the absence of a transfection reagent. Oligonucleotides 2010;20:225-30
45. Wibrand K, Pai B, Siripornmongcolchai T, et al. MicroRNA regulation of the synaptic plasticity-related gene Arc. PLoS One 2012;7:e41688
46. Torres AG, Threlfall RN, Gait MJ. Potent and sustained cellular inhibition of miR-122 by lysine-derivatized peptide nucleic acids (PNA) and phosphorothioate locked nucleic acid (LNA)/2-O-methyl (OMe) mixmer antimiRs in the absence of transfection agents. Artif DNA PNA XNA 2011;2:71-8
47. Torres AG, Fabani MM, Vigorito E, et al. Chemical structure requirements and cellular targeting of microRNA-122 by peptide nucleic acids anti-miRs. Nucleic Acids Res 2012;40:2152-67
48. Fabbri E, Manicardi A, Tedeschi T, et al. Modulation of the biological activity of microRNA-210 with peptide nucleic acids (PNAs). ChemMedChem 2011;6:2192-202. An important paper on applications of PNAs targeting microRNAs.
49. Brognara E, Fabbri E, Aimi F, et al. Peptide nucleic acids targeting miR-221 modulate p27Kip1 expression in breast cancer MDA-MB-231 cells. Int J Oncol 2012;41:2119-27.. An important paper on the biological activity of PNA targeting miR-221 in a breast cancer model system.
50. Manicardi A, Fabbri E, Tedeschi T, et al. Cellular uptakes, biostabilities and anti-miR-210 activities of chiral arginine-PNAs in leukaemic K562 cells. ChemBioChem 2012;13:1327-37
51. Brown PN, Yin H. PNA-based microRNA inhibitors elicit antiinflammatory effects in microglia cells. Chem Commun (Camb) 2013;49:4415-17
52. Park HK, Su Y. MicroRNA antisense pnas, compositions comprising the same, and methods for using and evaluating the same. US2010240058; 2010
53. Takeshi Haraguchi T, Iba H. Method for inhibiting function of microRNA. US2011245481; 2011
54. Olsen AG, Dahl O, Nielsen PE. Synthesis and evaluation of a conformationally constrained pyridazinone PNA-monomer for recognition of thymine in triple-helix structures. Bioorg Med Chem Lett 2004;14:1551-4
55. Olsen AG, Dahl O, Nielsen PE. A novel PNA-monomer for recognition of thymine in triple-helix structures. Nucleosides Nucleotides Nucleic Acids 2003;22:1331-3
56. Diviacco S, Rapozzi V, Xodo L, et al. Site-directed inhibition of DNA replication by triple helix formation. FASEB J 2001;15:2660-8
57. Betts L, Josey JA, Veal JM, Jordan SR. A nucleic acid triple helix formed by a peptide nucleic acid-DNA complex. Science 1995;270:1838-41
58. Boffa LC, Scarfi S, Mariani MR, et al. Dihydrotestosterone as a selective cellular/nuclear localization vector for anti-gene peptide nucleic acid in prostatic carcinoma cells. Cancer Res 2000;60:2258-62
59. Naesby M. Small triplex forming PNA oligos. EP0897991; 1999
60. Sugiyama T, Imamura Y, Hakamata W, et al. Cooperative strand invasion of double-stranded DNA by peptide nucleic acid. Nucleic Acids Symp Ser (Oxf) 2005;49:167-8
61. Yamamoto Y, Yoshida J, Tedeschi T, et al. Highly efficient strand invasion by peptide nucleic acid bearing optically pure lysine residues in its backbone. Nucleic Acids Symp Ser (Oxf) 2006;50:109-10
62. Rapireddy S, He G, Roy S, et al. Strand invasion of mixed-sequence B-DNA by acridine-linked, gamma-peptide nucleic acid (gamma-PNA). J Am Chem Soc 2007;129:15596-600
63. Ishizuka T, Otani K, Sumaoka J, Komiyama M. Strand invasion of conventional PNA to arbitrary sequence in DNA assisted by single-stranded DNA binding protein. Chem Commun (Camb) 2009;10:1225-7
64. Aiba Y, Komiyama M. Introduction of disulfide bond to the main chain of PNA to switch its hybridization and invasion activity. Org Biomol Chem 2009;7:5078-83
65. Yamazaki T, Aiba Y, Yasuda K, et al. Clear-cut observation of PNA invasion using nanomechanical DNA origami devices. Chem Commun (Camb) 2012;48:11361-3
66. Vickers T. Inhibition of transcription factor-mediated transcriptional activation by oligomer strand invasion. WO1996035705; 1996
67. Møllegaard NE, Buchardt O, Egholm M, Nielsen PE. Peptide nucleic acid.DNA strand displacement loops as artificial transcription promoters. Proc Natl Acad Sci USA 1994;91:3892-5
68. Stanojevic D. Artificial transcriptional factors and methods of use. WO2002031166; 2002
69. Pachuk JC, Satishchandran C. Transfection kinetics and structural promoters. WO2004094654; 2004
70. Rogers FA, Vasquez KM, Egholm M, Glazer PM. Site-directed recombination via bifunctional PNA-DNA conjugates. Proc Natl Acad Sci USA 2002;99:16695-700
71. Katada H, Komiyama M. Artificial restriction DNA cutters to promote homologous recombination in human cells. Curr Gene Ther 2011;11:38-45.. An important review paper on artificial rescriction DNA cutters outlining the application of this technology to increase the efficiency of homologous recombination.
72. Yamamoto Y, Uehara A, Miura K, et al. Development of artificial restriction DNA cutter composed of Ce(Iv)/EDTA and PNA. Nucleosides Nucleotides Nucleic Acids 2007;26:1265-8
73. Miyajima Y, Ishizuka T, Yamamoto Y, et al. Origin of high fidelity in targetsequence recognition by PNA-Ce(IV)/EDTA combinations as site-selective DNA cutters. J Am Chem Soc 2009;131:2657-62
74. Biet E, Dutreix M, Feugeas JP, et al. Methods and compositions for effecting homologous recombination. US6936418; 2005
75. Uhlmann E. Peptide nucleic acids (PNA) and PNA-DNA chimeras: From high binding affinity towards biological function. Biol Chem 1998;379:1045-52
76. Gildea B, Coull JM. PNA-DNA chimeras and PNA synthons for their preparation. WO1996040709; 1996
77. Finotti A, Borgatti M, Bezzerri V, et al. Effects of decoy molecules targeting NFkappaB transcription factors in Cystic fibrosis IB3-1 cells: Recruitment of NFkappaB to the IL-8 gene promoter and transcription of the IL-8 gene. Artif DNA PNA XNA 2012;3:97-296
78. Gambari R, Borgatti M, Bezzerri V, et al. Decoy oligodeoxyribonucleotides and peptide nucleic acids-DNA chimeras targeting nuclear factor kappa-B: Inhibition of IL-8 gene expression in cystic fibrosis cells infected with Pseudomonas aeruginosa. Biochem Pharmacol 2010;80:1887-94.. An important review on applications of PNA-based transcription factor decoy molecules.
79. Borgatti M, Boyd DD, Lampronti I, et al. Decoy molecules based on PNADNA chimeras and targeting Sp1 transcription factors inhibit the activity of urokinase-type plasminogen activator receptor (uPAR) promoter. Oncol Res 2005;15:373-83
80. Gambari R, Penolazzi L, Piva R. Double-stranded synthetic oligonucleotides useful for inducing apoptosis of osteoclasts for the treatment of osteopenic pathologies. US7659258; 2010.. An important patent on the use of PNAs as transcription decoy reagents for the treatment of osteopenic diseases.
81. Collard J, Sherman OK, Curna O. Treatment of transcription factor E3 (TFE3) and insulin receptor substrate 2 (IRS2) related diseases by inhibition of natural antisense transcript to TF3. US20120095079; 2012
82. Nielsen PE, Buchardt O, Egholm M, Berg RH. Peptide nucleic acids. US5539082; 1996.. A key patent on PNAs.
83. Buchardt O, Egholm M, Nielsen P, Berg R. Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility. US5714331; 1998.. A key patent on PNAbased applications.
84. Buchardt O, Egholm M, Nielsen P, Berg R. Peptide nucleic acids having amino acid side chains. US5719262; 1998
85. Hyldig-Nielsen JJ, Pluzek K-J. Antibody to PNA/nucleic acids complexes. US5612458; 1997
86. Nielsen P, Buchardt O, Lagriffoul P. Chiral peptide nucleic acid monomers and oligomers. US5977296; 1999
87. Demers DB. Method for enhancing amplification in the polymerase chain reaction employing peptide nucleic acids. US5629178; 1997
88. Uhlmann E, Breipohl G, Benner SA, Lutz M. Process for amplifying nucleic acids using DNA/PNA primers. US6063571; 2000
89. Park HK, Choi JJ. Method for selective labeling and detection of target nucleic acids using immobilized peptide nucleic acid probes. US20100248980; 2010
90. Lee H, Min JH. Synthesis of peptide nucleic acids conjugated with amino acids and their application. US20110014715; 2011
91. Ha J, Jang J, Kim I. PNA chip using plastic substrate coated with epoxy group-containing polymer, method of manufacturing the PNA chip, and method of detecting single nucleotide polymorphism using the PNA chip. US20060147949; 2006
92. Achim C, Shi H, Yeh JI. Biosensors and related methods. US20090061451; 2009. A key patent on PNA-based SPR.
93. Kyriaki S, Coull JM, Stender H, et al. Compositions for detecting target sequences. US7135563; 2006
94. Choi JJ, Park Hk. Peptide nucleic acid probes, kits and methods for expression profiling of microRNAs. US20110111416; 2011
95. Park HK, Choi JJ, Jang M, Kim J. PNA probes, kits and methods for Cytochrome P450 genotyping. WO2009125934; 2009
96. Choi JJ, Kim S, Lee H, Park HK. PNA probes, kits, and methods for detecting genotypes of human papillomavirus. US20080248461; 2008
97. Choi JJ, Kim S, Lee H, Park HK. PNA probes, kits, and methods for detecting lamivudine-resistant hepatitis B viruses. US20080233557; 2008
98. Park HK, Choi JJ, Cho MH. Method and kit for detecting BRAF mutant using real-time PCR clamping on the basis of PNA. WO2011093606; 2011
99. Park HK, Choi JJ. Method and kit for detecting EGFR mutation by using realtime PCR clamping. WO2011105732; 2011
100. Park HK, Choi JJ, Cho MH. Method and kit for detecting K-RAS mutant using real-time PCR clamping. WO2011049343; 2011
101. Park HK, Choi JJ, Cho MH. Method and kit for detecting BCR-ABL fusion gene mutation using real-time PCR clamping on the basis of PNA. WO2012064035; 2012
102. Van M, Dongen JJ, Pluzek K-J, et al. Methods and probes for the detection of chromosome aberrations. Methods and probes for the detection of chromosome aberrations. US20040043383; 2004
103. Taneja KL. Non-nucleic acid probes, probe sets, methods and kits pertaining to the detection of individual human chromosomes X, Y, 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 16, 17, 18 and 20 as 13/21 as a pair. US7981599; 2011
104. Hyldig-Nielsen JJ, Oliveira KM, Rigby S, Stender H. PNA Probes, probe sets, methods and kits pertaining to the detection of candida. US20120082980; 2012
105. Choi JJ, Ha SJ, Kim S, et al. Peptide nucleic acid oligomers comprising universal bases, preparation methods thereof, and kits, devices and methods for the analysis, detection or modulation of nucleic acids using the same. US20100292471; 2010
106. Lee J-O, Kim H-Y, Chung S, et al. Peptide nucleic acid derivatives with good cell penetration and strong affinity for nucleic acid. WO2009113828; 2009
107. Bennet CF, Felgner PL, Zelphati O. Chemical modification of DNA using peptide nucleic acid conjugates. US6165720; 2000
108. Cook PD. PNA-DNA-PNA chimeric macromolecules. US5700922; 1997
109. Clement JG. Treating and preventing hepatitis C virus infection using c-raf kinase antisense oligonucleotides. WO2011112516; 2011
110. Iversen PL. Antisense modulation of nuclear hormone receptors. US20110224283; 2011
111. Iversen PL, Mourich DV, Schnell FJ. Antisense modulation of interleukins 17 and 23 signaling. US20110289608; 2011
112. Collard J, Khorkova SO. Treatment of apolipoprotein-A1 related diseases by inhibition of natural antisense transcript to apolipoprotein-A1. US8153606; 2012
113. Collard J, Khorkova SO. Treatment of sirtuin (sirt) related diseases by inhibition of natural antisense transcript to a sirtuin (sirt). US20120252869; 2012
114. Collard J, Khorkova SO. Treatment of paraoxonase 1 (pon1) related diseases by inhibition of natural antisense transcript to pon1. US20120095081; 2012
115. Collard J, Khorkova SO. Treatment of bcl2-like 11 (bcl2l11) related diseases by inhibition of natural antisense transcript to bcl2l11. WO2011146674; 2011
116. Collard J, Khorkova SO. Treatment of fibroblast growth factor 21 (fgf21) related diseases by inhibition of natural antisense transcript to fgf21. US20130035373; 2013
117. Stein DA, Ge Q, Chen J, et al. Antisense antiviral compound and method for treating influenza viral infection. US8357664; 2013
118. Stein DA, Skilling DE, Iversen PL, Smith AW. Antisense antiviral agent and method for treating ssRNA viral infection. US6828105; 2004
119. Stein DA, Rijnbrand CA, Iversen PL, Weller DD. Antisense antiviral compound and method for treating picornavirus) infection. US8329668; 2012
120. Deere JD, Geller BL, Iversen PL, Weller DD. Antisense antibacterial method and compound. US7625873; 2009
121. Monia BP, Cowsert LM, McKay R. Antisense inhibition of PTEN expression. US6284538; 2001
122. Monia BP, Freier SM. Antisense inhibition of clusterin expression. US6383808; 2002
123. Cowsert LM, Monia BP. Antisense inhibition of MAP kinase kinase 6 expression. US6033910; 2000
124. Cowsert LM, Monia BP. Antisense modulation of liver glycogen phosphorylase expression. US6043091; 2002
125. Anderson KP, Baker B, Bennet F. Antisense inhibition of ICAM-1, Eselectin, and CMV IE1/IE2. US5789573; 1998
126. Desai N, Hwang L, Trieu V. Sparc antisense compositions and uses thereof. US20120183538; 2012
127. Feriotto G, Corradini R, Sforza S, et al. Peptide nucleic acids and biosensor technology for real-time detection of the cystic fibrosis W1282X mutation by surface plasmon resonance. Lab Invest 2001;81:1415-27.. A key paper on the applications of PNAs as probes in diagnostic protocols based on SPR. Sequence-specific nucleic acid detection from binary pore conductance measurement. J Am Chem Soc 2012;134:15880-6
128. J Am Chem Soc 2012;134:15880-6
129. Tonelli A, Tedeschi T, Germini A, et al. Real time RNA transcription monitoring by Thiazole Orange (TO)-conjugated Peptide Nucleic Acid (PNA) probes: Norovirus detection. Mol Biosyst 2011;7:1684-92
130. Malic S, Hill KE, Hayes A, et al. Detection and identification of specific bacteria in wound biofilms using peptide nucleic acid fluorescent in situ hybridization (PNA FISH). Microbiology 2009;155:2603-11
131. Kummer S, Knoll A, Socher E, et al. PNA FIT-probes for the dual color imaging of two viral mRNA targets in influenza H1N1 infected live cells. Bioconjug Chem 2012;23:2051-60
132. Skronski M, Chorostowska-Wynimko J, Szczepulska E, et al. Reliable detection of rare mutations in EGFR gene codon L858 by PNA-LNA PCR clamp in nonsmall cell lung cancer. Adv Exp Med Biol 2013;756:321-31
133. Reisberg S, Dang LA, Nguyen QA, et al. Label-free DNA electrochemical sensor based on a PNA-functionalized conductive polymer. Talanta 2008;76:206-10
134. Shiraishi T, Deborggraeve S, Buscher P, Nielsen PE. Sensitive detection of nucleic acids by PNA hybridization directed colocalization of fluorescent beads. Artif DNA PNA XNA 2011;2:60-6
135. Lee H, Kim A, Ahn IS, et al. Colorimetric detection of c-Kit mutations using electrostatic attraction induced aggregation of peptide nucleic acid modified gold nanoparticles. Chem Commun (Camb) 2011;47:11477-9
136. Nordga°rd O, Oltedal S, Janssen EA, et al. Comparison of a PNA clamp PCR and an ARMS/Scorpion PCR assay for the detection of K-ras mutations. Diagn Mol Pathol 2012;21:9-13
137. Choi YJ, Kim HJ, Shin HB, et al. Evaluation of peptide nucleic acid probebased real-time PCR for detection of Mycobacterium tuberculosis complex and nontuberculous mycobacteria in respiratory specimens. Ann Lab Med 2012;32:257-63
138. Su X, Teh HF, Aung KM, et al. Femtomol SPR detection of DNA-PNA hybridization with the assistance of DNA-guided polyaniline deposition. Biosens Bioelectron 2008;23:1715-20
139. Lao AI, Su X, Aung KM. SPR study of DNA hybridization with DNA and PNA probes under stringent conditions. Biosens Bioelectron 2009;24:1717-22
140. Ananthanawat C, Vilaivan T, Mekboonsonglarp W, Hoven VP. Thiolated pyrrolidinyl peptide nucleic acids for the detection of DNA hybridization using surface plasmon resonance. Biosens Bioelectron 2009;24:3544-9
141. Ananthanawat C, Vilaivan T, Hoven VP, Su X. Comparison of DNA, aminoethylglycyl PNA and pyrrolidinyl PNA as probes for detection of DNA hybridization using surface plasmon resonance technique. Biosens Bioelectron 2010;25:1064-9
142. Spova H, Homola J. Surface plasmon resonance sensing of nucleic acids: A review. Anal Chim Acta 2013;773:9-23.. An important review on SPR-based protocols in diagnostics.
143. Tomac S, Sarkar M, Ratilainen T, et al. A Ionic effects on the stability and conformation of peptide nucleic acid (PNA) complexes. J Am Chem Soc 1996;118:5544-52
144. Nielsen PE, Egholm M, Berg RH, Buchardt O. Peptide nucleic acids (PNA). Potential antisense and anti-gene agents. Anticancer Drug Des 1993;8:53-63.. An important review on applications of PNAs as gene expression modulators.
145. Weiler J, Gausepohl H, Hauser N, et al. Hybridisation based DNA screening on peptide nucleic acid (PNA) oligomer arrays. Nucleic Acids Res 1997;25:2792-9
146. DAgata R, Breveglieri G, Zanoli LM, et al. Direct detection of point mutations in nonamplified human genomic DNA. Anal Chem 2011;83:8711-17.. A key paper on the applications of PNAs as probes for PCR-free diagnosis based on SPR-Imaging.
147. Bergmann F, Bannwarth W, Tam S. Solid phase synthesis of directly linked PNA-DNA-hybrids. Tetrahedron Lett 1995;36:6823-6
148. Haaima G, Lohse A, Buchardt O, Nielsen PE. Peptide nucleic acids (PNA) containing thymine monomers derived from chiral amino acids: Hybridization and solubility properties of d-lysine PNA. Angew Chem 1996;35:1939-41
149. Lesnik E, Hassman F, Barbeau J, et al. Triplex formation between DNA and mixed purine-pyrimidine PNA analog with lysines in backbone. Nucleosides Nucleotides 1997;16:1775-9
150. Good L, Nielsen PE. Progress in developing PNA as a gene-targeted drug. Antisense Nucleic Acid Drug Dev 1997;7:431-7
151. Godskesen MA, Hyldig-Nielsen JJ. Detection of Ribosomal RNA using PNA probes. US5985563; 1999
152. Stender H, Lund K, Mollerup TA. Probes for the detection of mycobacteria. US6753421; 2004
153. Bergmann F, Herrmann R, Seidel C, Kocj T. Monomeric building blocks for labeling peptide nucleic acids. US6388061; 2002
154. Hyldig-Nielsen JJ, Just T, Pluzek KJ. In situ hybridization to detect specific nucleic acid sequences in eucaryotic samples. WO1997018325; 1997
155. Boukherroub R, Szunerits S. Chips for surface plasmon (SPR) detection. US8279444 B2; 2012.. A key patent on applications of PNAs to SPR-based diagnostic platforms.
156. Karube I, Nagata R, Sawata S. Method for detecting DNA with probe PNA. US20030165953; 2003
157. Zhang N, Appella DH. Advantages of peptide nucleic acids as diagnostic platforms for detection of nucleic acids in resource-limited settings. J Infect Dis 2010;201(Suppl 1):S42-5
158. Lansdorp PM, Verwoerd NP, Van De Rijke FM, et al. Heterogeneity in telomere length of human chromosomes. Hum Mol Genet 1996;5:685-91
159. Lansdorp P. Method for detecting multiple copies of a repeat sequence in a nucleic acid molecule. US20030022204; 1997
160. Berg RH, Buchardt O, Egholm M, Nielsen PE. Peptide nucleic acids. US5539082; 1996
161. Wang Z, Zhang K, Wooley KL, Taylor JS. Imaging mRNA expression in live cells via PNA•DNA strand displacement-activated probes. J Nucleic Acids 2012;2012:962652
162. Gasser G, Pinto A, Neumann S, et al. Synthesis, characterisation and bioimaging of a fluorescent rheniumcontaining PNA bioconjugate. Dalton Trans 2012;41:2304-13
163. Ryoo SR, Lee J, Yeo J, et al. Quantitative and multiplexed microRNA sensing in living cells based on peptide nucleic acid and nano graphene oxide (PANGO). ACS Nano 2013;7:5882-91
164. Pipkorn R, Wiessler M, Waldeck W, et al. Improved synthesis strategy for peptide nucleic acids (PNA) appropriate for cell-specific fluorescence imaging. Int J Med Sci 2012;9:1-10
165. Wiegant J, Brouwer AK, Tanke HJ, Dirks RW. Visualizing nucleic acids in living cells by fluorescence in vivo hybridization. Methods Mol Biol 2010;659:239-46
166. Tilsner J, Flors C. FIT for purpose: PNA-based probes enable mRNA imaging in living cells. ChemBioChem 2011;12:1007-9
167. Kam Y, Rubinstein A, Nissan A, et al. Detection of endogenous K-ras mRNA in living cells at a single base resolution by a PNA molecular beacon. Mol Pharm 2012;9:685-93
168. Kummer S, Knoll A, Socher E, et al. Fluorescence imaging of influenza H1N1 mRNA in living infected cells using single-chromophore FIT-PNA. Angew Chem Int Ed Engl 2011;50:1931-4
169. Segura J, Fillat C, Andreu D, et al. Monitoring gene therapy by external imaging of mRNA: Pilot study on murine erythropoietin. Ther Drug Monit 2007;29:612-18
170. Yaroslavsky AI, Smolina IV. Fluorescence imaging of single-copy DNA sequences within the human genome using PNAdirected padlock probe assembly. Chem Biol 2013;20:445-53
171. Kam Y, Rubinstein A, Naik S, et al. Detection of a long non-coding RNA (CCAT1) in living cells and human adenocarcinoma of colon tissues using FIT-PNA molecular beacons. Cancer Lett 2013;doi:pii: S0304-3835(13)00126-2
172. Wang Z, Zhang K, Shen Y, et al. Imaging mRNA expression levels in living cells with PNA•DNA binary FRET probes delivered by cationic shellcrosslinked nanoparticles. Org Biomol Chem 2013;11:3159-67
173. Sadhu KK, Winssinger N. Detection of miRNA in live cells by using templated RuII-catalyzed unmasking of a fluorophore. Chemistry (Easton) 2013;19:8182-9
174. Pianowski Z, Gorska K, Oswald L, et al. Imaging of mRNA in live cells using nucleic acid-templated reduction of azidorhodamine probes. J Am Chem Soc 2009;131:6492-7
175. Pianowski ZL, Winssinger N. Fluorescence-based detection of single nucleotide permutation in DNA via catalytically templated reaction. Chem Commun (Camb) 2007;37:3820-2
176. Franzini R, Kool ET. Reductive release probes containing a chemoselectively cleavable alpha-azidoether linker and methods of use thereof. US2012178086; 2012
177. Wickstrom E, Thakur ML, Edward R. Receptor-specific targeting with complementary peptide nucleic acids conjugated to peptide analogs and radionuclides. In: Janson CG, During MJ, editors. Peptide nucleic acids, morpholinos and related antisense biomolecules. Georgetown, Texas, USA; New York, NY, USA: Eurekah.com and Kluwer Academic/Plenum Publishers; 2006. p. 61-88
178. Amirkhanov NV, Zhang K, Aruva MR, et al. Imaging human pancreatic cancer xenografts by targeting mutant KRAS2 mRNA with [(111)In]DOTA(n)- poly(diamidopropanoyl)(m)-KRAS2 PNA-D(Cys-Ser-Lys-Cys) nanoparticles. Bioconjug Chem 2010;21:731-40
179. Tian X, Aruva MR, Zhang K, et al. PET imaging of CCND1 mRNA in human MCF7 estrogen receptor positive breast cancer xenografts with oncogene-specific [64Cu]chelator-peptide nucleic acid-IGF1 analog radiohybridization probes. J Nucl Med 2007;48:1699-707
180. Piva R, Penolazzi L, Lambertini E, et al. Induction of apoptosis of human primary osteoclasts treated with a transcription factor decoy mimicking a promoter region of estrogen receptor alpha. Apoptosis 2005;10:1079-94
181. Penolazzi L, Zennaro M, Lambertini E, et al. Induction of estrogen receptor alpha expression with decoy oligonucleotide targeted to NFATc1 binding sites in osteoblasts. Mol Pharmacol 2007;71:1457-62
182. Romanelli A, Pedone C, Saviano M, et al. Molecular interactions with nuclear factor kappaB (NF-kappaB) transcription factors of a PNA-DNA chimera mimicking NF-kappaB binding sites. Eur J Biochem 2001;268:6066-75.. The first paper showing transcription factor decoy activity of molecules based on PNA-DNA-PNA chimeras.
183. Available from: Http://clinicaltrials.gov/ct2/show/record/NCT01839604
184. Available from: Http://clinicaltrialsfeeds. org
185. Available from: Http://clinicaltrials.gov/ct2/show/record/NCT00159250
186. Available from: Http://clinicaltrials.gov/show/NCT00903461
187. Soomets U, Hallbrink M, Langel U. Antisense properties of peptide nucleic acids. Front Biosci 1999;4:D782-6
188. Doyle DF, Braasch DA, Simmons CG, et al. Inhibition of gene expression inside cells by peptide nucleic acids: Effect of mRNA target sequence, mismatched bases, and PNA length. Biochemistry 2001;40:53-64
189. Kaihatsu K, Huffman KE, Corey DR. Intracellular uptake and inhibition of gene expression by PNAs and PNApeptide conjugates. Biochemistry 2004;43:14340-7
190. Filipowicz W, Jaskiewicz L, Kolb FA, Pillai RS. Post-transcriptional gene silencing by siRNAs and miRNAs. Curr Opin Struct Biol 2005;15:331-41
191. He L, Hannon GJ. MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet 2010;5:522-31.. A key review on microRNAs.
192. Sontheimer EJ, Carthew RW. Silence from within: Endogenous siRNAs and miRNAs. Cell 2005;122:9-12
193. Alvarez-Garcia I, Miska EA. MicroRNA functions in animal development and human disease. Development 2005;132:4653-62
194. Zheng H, Fu R, Wang JT, et al. Advances in the techniques for the prediction of microRNA targets. Int J Mol Sci 2013;14:8179-87
195. Brown BD, Naldini L. Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat Rev Genet 2009;10:578-85
196. Czech MP. MicroRNAs as therapeutic targets. New Engl J Med 2006;354:1194-5
197. Kota SK, Balasubramanian S. Cancer therapy via modulation of micro RNA levels: A promising future. Drug Discov Today 2010;15:733-40
198. Wang Z. MicroRNA interference: An update. J Biol Med 2011;1:1-12
199. Krutzfeldt J, Rajewsky N, Braich R, et al. Silencing of microRNAs in vivo with antagomirs. Nature 2005;438:685-9
200. Fabani MM, Abreu-Goodger C, Williams D, et al. Efficient inhibition of miR-155 function in vivo by peptide nucleic acids. Nucleic Acids Res 2010;38:4466-75
201. Bianchi N, Zuccato C, Lampronti I, et al. Expression of miR-210 during erythroid differentiation and induction of gamma-globin gene expression. BMB Rep 2009;42:493-9
202. Nastruzzi C, Cortesi R, Esposito E, et al. Liposomes as carriers for DNA-PNA hybrids. J Control Release 2000;68:237-49
203. Zhou P, Dragulescu-Andrasi A, Bhattacharya B, et al. Synthesis of cellpermeable peptide nucleic acids and characterization of their hybridization and uptake properties. Bioorg Med Chem Lett 2006;16:4931-5
204. Sforza S, Tedeschi T, Calabretta A, et al. A peptide nucleic acid embedding a pseudopeptide nuclear localization sequence in the backbone behaves as a peptide mimic. Eur J Org Chem 2010;13:2441-4
205. Oh SY, Ju YS, Park H. A Highly effective and long-lasting inhibition of miRNA with PNA-based antisense oligonucleotides. Mol Cells 2009;28:341-5
206. Nielsen PE, Good L. Peptide nucleic acids having antibacterial activity. US6734161; 2004
207. Nielsen PE, Good L. Antibacterial and antibiotic methods using peptide nucleic acids and pharmaceutical compositions therefor. US6300318; 2001
208. Corey DR, Norton JC, Piatyszek MA, et al. Modulation of mammalian telomerase by peptide nucleic acids. US6015710; 2000
209. Grandis JR, Danith HLY, Thomas SM. Antisense guanidinium peptide nucleic acid (GPNA) oligonucleotides as antitumor agents. US7960360; 2011
210. Matthew TD, Neil LR, William TR. Gene therapy for mitochondrial DNA defects using peptide nucleic acids. WO1997041150; 1997
211. Mizrahi RA, Schirle NT, Beal PA. Potent and selective inhibition of A-to-I RNA editing with 2-O-methyl/locked nucleic acid-containing antisense oligoribonucleotides. ACS Chem Biol 2013;8:832-9
212. Zaghloul EM, Madsen AS, Moreno PM, et al. Optimizing anti-gene oligonucleotide Zorro-LNA for improved strand invasion into duplex DNA. Nucleic Acids Res 2011;39:1142-54
213. Stanton R, Sciabola S, Salatto C. Chemical modification study of antisense gapmers. Nucleic Acid Ther 2012;22:344-59
214. Emmrich S, Wang W, John K, et al. Antisense gapmers selectively suppress individual oncogenic p73 splice isoforms and inhibit tumor growth in vivo. Mol Cancer 2009;8:61
215. Comparison of sequencing and PNA clamping of EGFR gene in patients with non-small cell type lung cancer. Available from: Http://clinicaltrials.gov/show/ NCT01767974
216. Anticipative diagnosis of central venous catheter related bloodstream infections using biphasic PNA-FISH and gram stain/AOLC tests. Available from: Http://clinicaltrials.gov/show/NCT01481038
217. Chakrabarti A, Zhang K, Aruva MR, et al. Radiohybridization PET imaging of KRAS G12D mRNA expression in human pancreas cancer xenografts with [(64)Cu]DO3A-peptide nucleic acidpeptide nanoparticles. Cancer Biol Ther 2007;6:948-56
218. Gambari R. Alternative options for DNA-based experimental therapy of beta-thalassemia. Expert Opin Biol Ther 2012;12:443-62
219. Colosimo A, Guida V, Antonucci I, et al. Sequence-specific modification of a beta-thalassemia locus by small DNA fragments in human erythroid progenitor cells. Haematologica 2007;92:129-30
220. Chin JY, Kuan JY, Lonkar PS, et al. Correction of a splice-site mutation in the beta-globin gene stimulated by triplex-forming peptide nucleic acids. Proc Natl Acad Sci USA 2008;105:13514-19
221. Rogers FA, Lin SS, Hegan DC, et al. Targeted gene modification of hematopoietic progenitor cells in mice following systemic administration of a PNA-peptide conjugate. Mol Ther 2011, doi:10.1038/mt.2011.163
222. Chin JY, Reza F, Glazer PM. Triplex-forming peptide nucleic acids induce heritable elevations in gammaglobin expression in hematopoietic progenitor cells. Mol Ther 2013;21:580-7
223. Thiede C, Bayerdorffer E, Blasczyk R, et al. Simple and sensitive detection of mutations in the ras proto-oncogenes using PNA-mediated PCR clamping. Nucleic Acids Res 1996;24:983-4
224. Ellison G, Zhu G, Moulis A, et al. EGFR mutation testing in lung cancer: A review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol 2013;66:79-89
225. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-39
226. Miyazawa H, Tanaka T, Nagai Y, et al. Peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp-based detection test for gefitinib-refractory T790M epidermal growth factor receptor mutation. Cancer Sci 2008;99:595-600.. A key paper on the therapeutic oriented application of PNA-clamping.
227. Matsumoto H, Ohide A, Matsuda K, Fujimoto H. Highly sensitive method for detecting mutated gene. US20130005589; 2013