In vitro evolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies

RNA Biology

Volumn 13, Issue 12, 2016, Pages 1232-1245

  Lipi, Farhana ^a   Chen, Suxiang ^a,b   Chakravarthy, Madhuri ^a,b   Rakesh, Shilpa ^a   Veedu, Rakesh N ^a,b  

^a Western Australian Research Inst   (Australia)

^b MURDOCH UNIVERSITY   (Australia)

Author keywords

Aptamers; chemical antibodies; chemically modified aptamers; in vitro selection; modified nucleotides; nucleic acid ligands; SELEX

Indexed keywords

1,5 ANHYDRO HEXITOL NUCLEIC ACID; 2' AMINO APTAMER; 2' FLUORO APTAMER; 2' FLUROARABINO NUCLEIC ACID; 2' O METHYL NUCLEIC ACID; 4' THIO NUCLEIC ACID; APTAMER; BASE; BORANE DERIVATIVE; BORANOPHOSPHATE; IMIDAZOLE; LOCKED NUCLEIC ACID; NUCLEIC ACID; NUCLEOTIDE; NUCLEOTIDE BASE; PHOSPHATE; PHOSPHOROTHIOIC ACID; SLOW OFF RATE MODIFIED APTAMER; SPIEGELMER; SUGAR; THREOSE NUCLEIC ACID; UNCLASSIFIED DRUG; URIDINE; MOLECULAR LIBRARY;

CHEMICAL MODIFICATION; COMPARATIVE STUDY; EVOLUTION; HUMAN; IN VITRO STUDY; MOLECULAR LIBRARY; NUCLEIC ACID SYNTHESIS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SYSTEMATIC EVOLUTION OF LIGANDS BY EXPONENTIAL ENRICHMENT APTAMER TECHNIQUE; ANIMAL; CHEMISTRY; CONFORMATION; PHARMACOKINETICS; SYNTHESIS;

ANIMALS; APTAMERS, NUCLEOTIDE; HUMANS; NUCLEIC ACID CONFORMATION; SELEX APTAMER TECHNIQUE; SMALL MOLECULE LIBRARIES;

EID: 85003955457     PISSN: 15476286     EISSN: 15558584     Source Type: Journal    
DOI: 10.1080/15476286.2016.1236173     Document Type: Review

References (113)

1. Keefe AD, Pai S, Ellington A. Aptamers as therapeutics. Nat Rev Drug Discov 2010; 9:537-50; PMID:20592747; http://dx.doi.org/10.1038/nrd3141
2. Nimjee SM, Rusconi CP, Sullenger BA. Aptamers:an emerging class of therapeutics. Annu Rev Med 2005; 56:555-83; PMID:15660527; http://dx.doi.org/10.1146/annurev.med.56.062904.144915
3. Famulok M, Hartig JS, Mayer G. Functional aptamers and aptazymes in biotechnology, diagnostics, and therapy. Chem Rev 2007; 107:3715-43; PMID:17715981; http://dx.doi.org/10.1021/cr0306743
4. Veedu RN. Editorial (Thematic Issue:Medicinal Chemistry of Aptamers). Curr Top Med Chem 2015; 15:1065; PMID:25866280; http://dx.doi.org/10.2174/1568026615666150413161707
5. Jayasena SD. Aptamers:an emerging class of molecules that rival antibodies in diagnostics. Clin Chem 1999; 45:1628-50; PMID:10471678
6. Stoltenburg R, Reinemann C, Strehlitz B. SELEX—a (r) evolutionary method to generate high-affinity nucleic acid ligands. Biomol Eng 2007; 24:381-403; PMID:17627883; http://dx.doi.org/10.1016/j.bioeng.2007.06.001
7. Gopinath SCB. Methods developed for SELEX. Anal Bioanal Chem 2007; 387:171-82; PMID:17072603; http://dx.doi.org/10.1007/s00216-006-0826-2
8. Demarest SJ, Glaser SM. Antibody therapeutics, antibody engineering, and the merits of protein stability. Curr Opin Drug Discov Devel 2008; 11:675-87; PMID:18729019
9. Ng EWM, Shima DT, Calias P, Cunningham ET, Guyer DR, Adamis AP. Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov 2006; 5:123-32; PMID:16518379; http://dx.doi.org/10.1038/nrd1955
10. Group MDRS. A phase II randomized double-masked trial of pegaptanib, an anti–vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 2005; 112:1747-57; PMID:16154196; http://dx.doi.org/10.1016/j.ophtha.2005.06.007
11. Kanwar JR, Roy K, Maremanda NG, Subramanian K, Veedu RN, Bawa R, Kanwar RK. Nucleic acid-based aptamers:applications, development and clinical trials. Curr Med Chem 2015; 22:2539-57; PMID:25723512; http://dx.doi.org/10.2174/0929867322666150227144909
12. Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 2003; 31:3406-15; PMID:12824337; http://dx.doi.org/10.1093/nar/gkg595
13. Hofacker IL. Vienna RNA secondary structure server. Nucleic Acids Res 2003; 31:3429-31; PMID:12824340; http://dx.doi.org/10.1093/nar/gkg599
14. Diafa S, Hollenstein M. Generation of aptamers with an expanded chemical repertoire. Molecules 2015; 20:16643-71; PMID:26389865; http://dx.doi.org/10.3390/molecules200916643
15. Dellafiore MA, Montserrat JM, Iribarren AM. Modified Nucleoside Triphosphates for In-vitro Selection Techniques. Front Chem 2016; 4:18; PMID:27200340; http://dx.doi.org/10.3389/fchem.2016.00018
16. Kong D, Yeung W, Hili R. Generation of Synthetic Copolymer Libraries by Combinatorial Assembly on Nucleic Acid Templates. ACS Comb Sci 2016; 18:355-70; PMID:27275512; http://dx.doi.org/10.1021/acscombsci.6b00059
17. Lapa SA, Chudinov AV, Timofeev EN. The toolbox for modified aptamers. Mol Biotechnol 2016; 58:79-92; PMID:26607475; http://dx.doi.org/10.1007/s12033-015-9907-9
18. Rohloff JC, Gelinas AD, Jarvis TC, Ochsner UA, Schneider DJ, Gold L, Janjic N. Nucleic acid ligands with protein-like side chains:modified aptamers and their use as diagnostic and therapeutic agents. Mol Ther Nucleic Acids 2014; 3:e201; PMID:25291143; http://dx.doi.org/10.1038/mtna.2014.49
19. Lauridsen LH, Rothnagel JA, Veedu RN. Enzymatic recognition of 2′‐modified ribonucleoside 5′‐triphosphates:Towards the evolution of versatile aptamers. ChemBioChem 2012; 13:19-25; PMID:22162282; http://dx.doi.org/10.1002/cbic.201100648
20. Loakes D, Holliger P. Polymerase engineering:towards the encoded synthesis of unnatural biopolymers. Chem Commun 2009:4619-31; PMID:19641798; http://dx.doi.org/10.1039/b903307f
21. Aschenbrenner J, Marx A. Direct and site-specific quantification of RNA 2′-O-methylation by PCR with an engineered DNA polymerase. Nucleic Acids Res 2016; 44:3495-502; PMID:27016740; http://dx.doi.org/10.1093/nar/gkw200
22. Elle IC, Karlsen KK, Terp MG, Larsen N, Nielsen R, Derbyshire N, Mandrup S, Ditzel HJ, Wengel J. Selection of LNA-containing DNA aptamers against recombinant human CD73. Mol Biosyst 2015; 11:1260-70; PMID:25720604; http://dx.doi.org/10.1039/C5MB00045A
23. Kasahara Y, Irisawa Y, Ozaki H, Obika S, Kuwahara M. 2′, 4′-BNA/LNA aptamers:CE-SELEX using a DNA-based library of full-length 2′-O, 4′-C-methylene-bridged/linked bicyclic ribonucleotides. Bioorg Med Chem Lett 2013; 23:1288-92; PMID:23374873; http://dx.doi.org/10.1016/j.bmcl.2012.12.093
24. Lauridsen LH, Shamaileh HA, Edwards SL, Taran E, Veedu RN. Rapid one-step selection method for generating nucleic acid aptamers:Development of a DNA aptamer against α-bungarotoxin. PLoS One 2012; 7:e41702; PMID:22860007; http://dx.doi.org/10.1371/journal.pone.0041702
25. Nitsche A, Kurth A, Dunkhorst A, Pänke O, Sielaff H, Junge W, Muth D, Scheller F, Stöcklein W, Dahmen C, et al. One-step selection of Vaccinia virus-binding DNA aptamers by MonoLEX. BMC Biotechnol 2007; 7(1):48; PMID:17199888; http://dx.doi.org/10.1186/1472-6750-7-48
26. Peng L, Stephens BJ, Bonin K, Cubicciotti R, Guthold M. A combined atomic force/fluorescence microscopy technique to select aptamers in a single cycle from a small pool of random oligonucleotides. Microsc Res Tech 2007; 70:372-81; PMID:17262788; http://dx.doi.org/10.1002/jemt.20421
27. Fan M, McBurnett SR, Andrews CJ, Allman AM, Bruno JG, Kiel JL. Aptamer selection express:a novel method for rapid single-step selection and sensing of aptamers. J Biomol Tech 2008; 19:311; PMID:19183794
28. Lin Y, Qiu Q, Gill SC, Jayasena SD. Modified RNA sequence pools for in vitro selection. Nucleic Acids Res 1994; 22:5229-34; PMID:7529404; http://dx.doi.org/10.1093/nar/22.24.5229
29. Green LS, Jellinek D, Bell C, Beebe LA, Feistner BD, Gill SC, Jucker FM, Janjić N. Nuclease-resistant nucleic acid ligands to vascular permeability factor/vascular endothelial growth factor. Chem Biol 1995; 2:683-95; PMID:9383475; http://dx.doi.org/10.1016/1074-5521(95)90032-2
30. Beaudry A, DeFoe J, Zinnen S, Burgin A, Beigelman L. In vitro selection of a novel nuclease-resistant RNA phosphodiesterase. Chem Biol 2000; 7:323-34; PMID:10801472; http://dx.doi.org/10.1016/S1074-5521(00)00110-1
31. Jellinek D, Green LS, Bell C, Lynott CK, Gill N, Vargeese C, Kirschenheuter G, McGee DP, Abesinghe P. Potent 2′-amino-2′-deoxypyrimidine RNA inhibitors of basic fibroblast growth factor. Biochemistry 1995; 34:11363-72; PMID:7547864; http://dx.doi.org/10.1021/bi00036a009
32. Bugaut A, Toulmé J-J, Rayner B. SELEX and dynamic combinatorial chemistry interplay for the selection of conjugated RNA aptamers. Org Biomol Chem 2006; 4:4082-8; PMID:17312962; http://dx.doi.org/10.1039/b610890c
33. Ruckman J, Green LS, Beeson J, Waugh S, Gillette WL, Henninger DD, Claesson-Welsh L, Janjic N. 2′-Fluoropyrimidine RNA-based aptamers to the 165-amino acid form of vascular endothelial growth factor (VEGF165). Inhibition of receptor binding and VEGF-induced vascular permeability through interactions requiring the exon 7-encoded domain. J Biol Chem 1998; 273:20556-67; PMID:9685413; http://dx.doi.org/10.1074/jbc.273.32.20556
34. Lupold SE, Hicke BJ, Lin Y, Coffey DS. Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. Cancer Res 2002; 62:4029-33; PMID:12124337; http://dx.doi.org/10.1158/0008-5472.can-12-2152
35. McNamara JO, Andrechek ER, Wang Y, Viles KD, Rempel RE, Gilboa E, Sullenger BA, Giangrande PH. Cell type–specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol 2006; 24:1005-15; PMID:16823371; http://dx.doi.org/10.1038/nbt1223
36. Biesecker G, Dihel L, Enney K, Bendele RA. Derivation of RNA aptamer inhibitors of human complement C5. Immunopharmacology 1999; 42:219-30; PMID:10408383; http://dx.doi.org/10.1016/S0162-3109(99)00020-X
37. Layzer JM, Sullenger BA. Simultaneous generation of aptamers to multiple gamma-carboxyglutamic acid proteins from a focused aptamer library using DeSELEX and convergent selection. Oligonucleotides 2007; 17:1-11; PMID:17461758; http://dx.doi.org/10.1089/oli.2006.0059
38. Rusconi CP, Scardino E, Layzer J, Pitoc GA, Ortel TL, Monroe D, Sullenger BA. RNA aptamers as reversible antagonists of coagulation factor IXa. Nature 2002; 419:90-4; PMID:12214238; http://dx.doi.org/10.1038/nature00963
39. Lamberti I, Scarano S, Esposito CL, Antoccia A, Antonini G, Tanzarella C, De Franciscis V, Minunni M. In vitro selection of RNA aptamers against CA125 tumor marker in ovarian cancer and its study by optical biosensing. Methods 2016; 97:58-68; PMID:26542762; http://dx.doi.org/10.1016/j.ymeth.2015.10.022
40. Kubik MF, Bell C, Fitzwater T, Watson SR, Tasset DM. Isolation and characterization of 2′-fluoro-, 2′-amino-, and 2′-fluoro-/amino-modified RNA ligands to human IFN-gamma that inhibit receptor binding. J Immunol 1997; 159:259-67; PMID:9200462
41. Pagratis NC, Bell C, Chang Y-F, Jennings S, Fitzwater T, Jellinek D, Dang C. Potent 2′-amino-, and 2′-fluoro-2′-deoxyribonucleotide RNA inhibitors of keratinocyte growth factor. Nat Biotechnol 1997; 15:68-73; PMID:9035109; http://dx.doi.org/10.1038/nbt0197-68
42. Burmeister PE, Lewis SD, Silva RF, Preiss JR, Horwitz LR, Pendergrast PS, McCauley TG, Kurz JC, Epstein DM, Wilson C. Direct in vitro selection of a 2′-O-methyl aptamer to VEGF. Chem Biol 2005; 12:25-33; PMID:15664512; http://dx.doi.org/10.1016/j.chembiol.2004.10.017
43. Burmeister PE, Wang C, Killough JR, Lewis SD, Horwitz LR, Ferguson A, Thompson KM, Pendergrast PS, McCauley TG, Kurz M. 2-Deoxy purine, 2-O-methyl pyrimidine (dRmY) aptamers as candidate therapeutics. Oligonucleotides 2006; 16:337-51; PMID:17155909; http://dx.doi.org/10.1089/oli.2006.16.337
44. Waters EK, Genga RM, Schwartz MC, Nelson JA, Schaub RG, Olson KA, Kurz JC, McGinness KE. Aptamer ARC19499 mediates a procoagulant hemostatic effect by inhibiting tissue factor pathway inhibitor. Blood 2011; 117:5514-22; PMID:21389323; http://dx.doi.org/10.1182/blood-2010-10-311936
45. Chelliserrykattil J, Ellington A. Evolution of a T7 RNA polymerase variant that transcribes 2′-O-methyl RNA. Nat Biotechnol 2004; 22:1155-60; PMID:15300257; http://dx.doi.org/10.1038/nbt1001
46. Fa M, Radeghieri A, Henry AA, Romesberg FE. Expanding the substrate repertoire of a DNA polymerase by directed evolution. J Am Chem Soc 2004; 126:1748-54; PMID:14871106; http://dx.doi.org/10.1021/ja038525p
47. Siegmund V, Santner T, Micura R, Marx A. Screening mutant libraries of T7 RNA polymerase for candidates with increased acceptance of 2′-modified nucleotides. Chem Commun 2012; 48:9870-2; PMID:22932771; http://dx.doi.org/10.1039/c2cc35028a
48. Padilla R, Sousa R. A Y639F/H784A T7 RNA polymerase double mutant displays superior properties for synthesizing RNAs with non‐canonical NTPs. Nucleic Acids Res 2002; 30:e138-e; PMID:12490729; http://dx.doi.org/10.1093/nar/gnf138
49. Wu Y, Sefah K, Liu H, Wang R, Tan W. DNA aptamer–micelle as an efficient detection/delivery vehicle toward cancer cells. Proc Natl Acad Sci 2010; 107:5-10; PMID:20080797; http://dx.doi.org/10.1073/pnas.0909611107
50. Kato Y, Minakawa N, Komatsu Y, Kamiya H, Ogawa N, Harashima H, Matsuda A. New NTP analogs:the synthesis of 4′-thioUTP and 4′-thioCTP and their utility for SELEX. Nucleic Acids Res 2005; 33:2942-51; PMID:15914669; http://dx.doi.org/10.1093/nar/gki578
51. Ferreira-Bravo IA, Cozens C, Holliger P, DeStefano JJ. Selection of 2′-deoxy-2′-fluoroarabinonucleotide (FANA) aptamers that bind HIV-1 reverse transcriptase with picomolar affinity. Nucleic Acids Res 2015; 43:9587-99; PMID:26476448; http://dx.doi.org/10.1093/nar/gkv1057
52. Pinheiro VB, Taylor AI, Cozens C, Abramov M, Renders M, Zhang S, Chaput JC, Wengel J, Peak-Chew S-Y, McLaughlin SH. Synthetic genetic polymers capable of heredity and evolution. Science 2012; 336:341-4; PMID:22517858; http://dx.doi.org/10.1126/science.1217622
53. Yu H, Zhang S, Chaput JC. Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor. Nat Chem 2012; 4:183-7; PMID:22354431; http://dx.doi.org/10.1038/nchem.1241
54. Yu H, Zhang S, Dunn MR, Chaput JC. An efficient and faithful in vitro replication system for threose nucleic acid. J Am Chem Soc 2013; 135:3583-91; PMID:23432469; http://dx.doi.org/10.1021/ja3118703
55. Larsen AC, Dunn MR, Hatch A, Sau SP, Youngbull C, Chaput JC. A general strategy for expanding polymerase function by droplet microfluidics. Nat Commun 2016; 7:11235; PMID:27044725; http://dx.doi.org/10.1038/ncomms11235
56. Veedu RN, Vester B, Wengel J. In vitro incorporation of LNA nucleotides. Nucleosides Nucleotides Nucleic Acids 2007; 26:1207-10; PMID:18058567; http://dx.doi.org/10.1080/15257770701527844
57. Veedu RN, Vester B, Wengel J. Novel applications of locked nucleic acids. Nucleic Acids Symp Ser:Oxford Univ Press, 2007; 51(1):29-30; PMID:18029570; http://dx.doi.org/10.1093/nass/nrm015
58. Veedu RN, Vester B, Wengel J. Enzymatic incorporation of LNA nucleotides into DNA strands. ChemBioChem 2007; 8:490-2; PMID:17315250; http://dx.doi.org/10.1002/cbic.200600501
59. Veedu RN, Vester B, Wengel J. Polymerase chain reaction and transcription using locked nucleic acid nucleotide triphosphates. J Am Chem Soc 2008; 130:8124-5; PMID:18533656; http://dx.doi.org/10.1021/ja801389n
60. Veedu RN, Vester B, Wengel J. Efficient enzymatic synthesis of LNA-modified DNA duplexes using KOD DNA polymerase. Org Biomol Chem 2009; 7:1404-9; PMID:19300826; http://dx.doi.org/10.1039/b819946a
61. Veedu RN, Wengel J. Locked nucleic acid nucleoside triphosphates and polymerases:on the way towards evolution of LNA aptamers. Mol Biosyst 2009; 5:787-92; PMID:19603111; http://dx.doi.org/10.1039/b905513b
62. Veedu RN, Wengel J. Locked nucleic acids:promising nucleic acid analogs for therapeutic applications. Chem Biodivers 2010; 7:536-42; PMID:20232325; http://dx.doi.org/10.1002/cbdv.200900343
63. Veedu RN, Wengel J. Locked nucleic acid as a novel class of therapeutic agents. RNA Biol 2009; 6:321-3; PMID:19458498; http://dx.doi.org/10.4161/rna.6.3.8807
64. Crouzier L, Dubois C, Edwards SL, Lauridsen LH, Wengel J, Veedu RN. Efficient reverse transcription using locked nucleic acid nucleotides towards the evolution of nuclease resistant RNA aptamers. PLoS One 2012; 7:e35990; PMID:22558297; http://dx.doi.org/10.1371/journal.pone.0035990
65. Højland T, Veedu RN, Vester B, Wengel J. Enzymatic synthesis of DNA strands containing α-L-LNA (α-L-configured locked nucleic acid) thymine nucleotides. Artif DNA PNA XNA 2012; 3:14-21; PMID:22679529; http://dx.doi.org/10.4161/adna.19272
66. Johannsen MW, Veedu RN, Madsen AS, Wengel J. Enzymatic polymerisation involving 2′-amino-LNA nucleotides. Bioorg Med Chem Lett 2012; 22:3522-6; PMID:22503454; http://dx.doi.org/10.1016/j.bmcl.2012.03.073
67. Veedu RN, Vester B, Wengel J. Polymerase directed incorporation studies of LNA-G nucleoside 5′-triphosphate and primer extension involving all four LNA nucleotides. New J Chem 2010; 34:877-9; http://dx.doi.org/10.1039/b9nj00628a
68. Wheeler M, Chardon A, Goubet A, Morihiro K, Tsan SY, Edwards SL, Kodama T, Obika S, Veedu RN. Synthesis of selenomethylene-locked nucleic acid (SeLNA)-modified oligonucleotides by polymerases. Chem Commun 2012; 48:11020-2; PMID:23042489; http://dx.doi.org/10.1039/c2cc36464f
69. Kuwahara M, Obika S, Nagashima J-i, Ohta Y, Suto Y, Ozaki H, Sawai H, Imanishi T. Systematic analysis of enzymatic DNA polymerization using oligo-DNA templates and triphosphate analogs involving 2′, 4′-bridged nucleosides. Nucleic Acids Res 2008; 36:4257-65; PMID:18583360; http://dx.doi.org/10.1093/nar/gkn404
70. Kasahara Y, Irisawa Y, Fujita H, Yahara A, Ozaki H, Obika S, Kuwahara M. Capillary electrophoresis–systematic evolution of ligands by exponential enrichment selection of base- and sugar-modified DNA aptamers:target binding dominated by 2′-O, 4′-C-methylene-bridged/locked nucleic acid primer. Anal Chem 2013; 85:4961-7; PMID:23662585; http://dx.doi.org/10.1021/ac400058z
71. Klussmann S, Nolte A, Bald R, Erdmann VA, Fürste JP. Mirror-image RNA that binds D-adenosine. Nat Biotechnol 1996; 14:1112-5; PMID:9631061; http://dx.doi.org/10.1038/nbt0996-1112
72. Nolte A, Klussmann S, Bald R, Erdmann VA, Fürste JP. Mirror-design of L-oligonucleotide ligands binding to L-arginine. Nat Biotechnol 1996; 14:1116-9; PMID:9631062; http://dx.doi.org/10.1038/nbt0996-1116
73. Williams KP, Liu X-H, Schumacher TNM, Lin HY, Ausiello DA, Kim PS, Bartel DP. Bioactive and nuclease-resistant L-DNA ligand of vasopressin. Proc Natl Acad Sci 1997; 94:11285-90; PMID:9326601; http://dx.doi.org/10.1073/pnas.94.21.11285
74. Purschke WG, Radtke F, Kleinjung F, Klussmann S. A DNA Spiegelmer to staphylococcal enterotoxin B. Nucleic Acids Res 2003; 31:3027-32; PMID:12799428; http://dx.doi.org/10.1093/nar/gkg413
75. Vater A, Jarosch F, Buchner K, Klussmann S. Short bioactive Spiegelmers to migraine‐associated calcitonin gene‐related peptide rapidly identified by a novel approach:Tailored‐SELEX. Nucleic Acids Res 2003; 31:e130-e; PMID:14576330; http://dx.doi.org/10.1093/nar/gng130
76. Eulberg D, Buchner K, Maasch C, Klussmann S. Development of an automated in vitro selection protocol to obtain RNA-based aptamers:identification of a biostable substance P antagonist. Nucleic Acids Res 2005; 33:e45-e; PMID:15745995; http://dx.doi.org/10.1093/nar/gni044
77. Faulhammer D, Eschgaller B, Stark S, Burgstaller P, Englberger W, Erfurth J, Kleinjung F, Rupp J, Vulcu SD, Schroder W. Biostable aptamers with antagonistic properties to the neuropeptide nociceptin/orphanin FQ. RNA 2004; 10:516-27; PMID:14970396; http://dx.doi.org/10.1261/rna.5186504
78. Leva S, Lichte A, Burmeister J, Muhn P, Jahnke B, Fesser D, Erfurth J, Burgstaller P, Klussmann S. GnRH binding RNA and DNA Spiegelmers:a novel approach toward GnRH antagonism. Chem Biol 2002; 9:351-9; PMID:11927260; http://dx.doi.org/10.1016/S1074-5521(02)00111-4
79. Jarosch F, Buchner K, Klussmann S. In vitro selection using a dual RNA library that allows primerless selection. Nucleic Acids Res 2006; 34:e86-e; PMID:16855281; http://dx.doi.org/10.1093/nar/gkl463
80. Helmling S, Maasch C, Eulberg D, Buchner K, Schröder W, Lange C, Vonhoff S, Wlotzka B, Tschöp MH, Rosewicz S. Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer. Proc Natl Acad Sci U S A 2004; 101:13174-9; PMID:15329412; http://dx.doi.org/10.1073/pnas.0404175101
81. Sundaram P, Kurniawan H, Byrne ME, Wower J. Therapeutic RNA aptamers in clinical trials. Eur J Pharm Sci 2013; 48:259-71; PMID:23142634; http://dx.doi.org/10.1016/j.ejps.2012.10.014
82. 2016 NPA. NOXXON Pharma AG 2016.
83. Yatime L, Maasch C, Hoehlig K, Klussmann S, Andersen GR, Vater A. Structural basis for the targeting of complement anaphylatoxin C5a using a mixed L-RNA/L-DNA aptamer. Nat Commun 2015; 6:6481; PMID:25901944; http://dx.doi.org/10.1038/ncomms7481
84. Wang Z, Xu W, Liu L, Zhu TF. A synthetic molecular system capable of mirror-image genetic replication and transcription. Nat Chem 2016; 8:698-704; PMID:27325097; http://dx.doi.org/10.1038/nchem.2517
85. Kuwahara M, Nagashima J-i, Hasegawa M, Tamura T, Kitagata R, Hanawa K, Hososhima S-i, Kasamatsu T, Ozaki H, Sawai H. Systematic characterization of 2′-deoxynucleoside-5′-triphosphate analogs as substrates for DNA polymerases by polymerase chain reaction and kinetic studies on enzymatic production of modified DNA. Nucleic Acids Res 2006; 34:5383-94; PMID:17012278; http://dx.doi.org/10.1093/nar/gkl637
86. MacPherson IS, Temme JS, Habeshian S, Felczak K, Pankiewicz K, Hedstrom L, Krauss IJ. Multivalent glycocluster design through directed evolution. Angew Chem Int Ed 2011; 50:11238-42; PMID:22191092; http://dx.doi.org/10.1002/anie.201105555
87. Temme JS, MacPherson IS, DeCourcey JF, Krauss IJ. High temperature SELMA:Evolution of DNA-supported oligomannose clusters which are tightly recognized by HIV bnAb 2G12. J Am Chem Soc 2014; 136:1726-9; PMID:24446826; http://dx.doi.org/10.1021/ja411212q
88. Tolle F, Brändle GM, Matzner D, Mayer G. A Versatile approach towards nucleobase‐modified aptamers. Angew Chem Int Ed 2015; 54:10971-4; PMID:26224087; http://dx.doi.org/10.1002/anie.201503652
89. Horiya S, MacPherson IS, Krauss IJ. Recent strategies targeting HIV glycans in vaccine design. Nat Chem Biol 2014; 10:990-9; PMID:25393493; http://dx.doi.org/10.1038/nchembio.1685
90. Temme JS, Drzyzga MG, MacPherson IS, Krauss IJ. Directed Evolution of 2G12‐Targeted Nonamannose Glycoclusters by SELMA. Chem Eur J 2013; 19:17291-5; PMID:24227340; http://dx.doi.org/10.1002/chem.201303848
91. Veedu R, Burri H, Kumar P, Sharma P, Hrdlicka P, Vester B, Wengel J. Polymerase-directed synthesis of C5-ethynyl locked nucleic acids. Bioorg Med Chem Lett 2010; 20:6565-8; PMID:20932755; http://dx.doi.org/10.1016/j.bmcl.2010.09.044
92. Zhang L, Yang Z, Sefah K, Bradley KM, Hoshika S, Kim M-J, Kim H-J, Zhu G, Jiménez E, Cansiz S. Evolution of functional six-nucleotide DNA. J Am Chem Soc 2015; 137:6734-7; PMID:25966323; http://dx.doi.org/10.1021/jacs.5b02251
93. Thyer R, Ellefson J. Synthetic biology:New letters for life's alphabet. Nature 2014; 509:291-2; PMID:24805244; http://dx.doi.org/10.1038/nature13335
94. Sefah K, Yang Z, Bradley KM, Hoshika S, Jiménez E, Zhang L, Zhu G, Shanker S, Yu F, Turek D. In vitro selection with artificial expanded genetic information systems. Proc Natl Acad Sci 2014; 111:1449-54; PMID:24379378; http://dx.doi.org/10.1073/pnas.1311778111
95. Georgiadis MM, Singh I, Kellett WF, Hoshika S, Benner SA, Richards NG. Structural basis for a six nucleotide genetic alphabet. J Am Chem Soc 2015; 137:6947-55; PMID:25961938; http://dx.doi.org/10.1021/jacs.5b03482
96. Latham JA, Johnson R, Toole JJ. The application of a modified nucleotide in aptamer selection:novel thrombin aptamers containing-(1-pentynyl)-2′-deoxyuridine. Nucleic Acids Res 1994; 22:2817-22; PMID:7519769; http://dx.doi.org/10.1093/nar/22.14.2817
97. Jensen KB, Atkinson BL, Willis MC, Koch TH, Gold L. Using in vitro selection to direct the covalent attachment of human immunodeficiency virus type 1 Rev protein to high-affinity RNA ligands. Proc Natl Acad Sci 1995; 92:12220-4; PMID:8618873; http://dx.doi.org/10.1073/pnas.92.26.12220
98. Battersby TR, Ang DN, Burgstaller P, Jurczyk SC, Bowser MT, Buchanan DD, Kennedy RT, Benner SA. Quantitative analysis of receptors for adenosine nucleotides obtained via in vitro selection from a library incorporating a cationic nucleotide analog. J Am Chem Soc 1999; 121:9781-9; PMID:11543572; http://dx.doi.org/10.1021/ja9816436
99. Vaish NK, Larralde R, Fraley AW, Szostak JW, McLaughlin LW. A novel, modification-dependent ATP-binding aptamer selected from an RNA library incorporating a cationic functionality. Biochemistry 2003; 42:8842-51; PMID:12873145; http://dx.doi.org/10.1021/bi027354i
100. Shoji A, Kuwahara M, Ozaki H, Sawai H. Modified DNA aptamer that binds the (R)-isomer of a thalidomide derivative with high enantioselectivity. J Am Chem Soc 2007; 129:1456-64; PMID:17263432; http://dx.doi.org/10.1021/ja067098n
101. Imaizumi Y, Kasahara Y, Fujita H, Kitadume S, Ozaki H, Endoh T, Kuwahara M, Sugimoto N. Efficacy of base-modification on target binding of small molecule DNA aptamers. J Am Chem Soc 2013; 135:9412-9; PMID:23734784; http://dx.doi.org/10.1021/ja4012222
102. Li M, Lin N, Huang Z, Du L, Altier C, Fang H, Wang B. Selecting aptamers for a glycoprotein through the incorporation of the boronic acid moiety. J Am Chem Soc 2008; 130:12636-8; PMID:18763762; http://dx.doi.org/10.1021/ja801510d
103. Vaught JD, Bock C, Carter J, Fitzwater T, Otis M, Schneider D, Rolando J, Waugh S, Wilcox SK, Eaton BE. Expanding the chemistry of DNA for in vitro selection. J Am Chem Soc 2010; 132:4141-51; PMID:20201573; http://dx.doi.org/10.1021/ja908035g
104. Santoro SW, Joyce GF, Sakthivel K, Gramatikova S, Barbas CF. RNA cleavage by a DNA enzyme with extended chemical functionality. J Am Chem Soc 2000; 122:2433-9; PMID:11543272; http://dx.doi.org/10.1021/ja993688s
105. Kimoto M, Yamashige R, Matsunaga K-i, Yokoyama S, Hirao I. Generation of high-affinity DNA aptamers using an expanded genetic alphabet. Nat Biotechnol 2013; 31:453-7; PMID:23563318; http://dx.doi.org/10.1038/nbt.2556
106. Hollenstein M, Hipolito CJ, Lam CH, Perrin DM. Toward the combinatorial selection of chemically modified DNAzyme RNase A mimics active against all-RNA substrates. ACS Comb Sci 2013; 15:174-82; PMID:23485334; http://dx.doi.org/10.1021/co3001378
107. Gold L, Ayers D, Bertino J, Bock C, Bock A, Brody EN, Carter J, Dalby AB, Eaton BE, Fitzwater T. Aptamer-based multiplexed proteomic technology for biomarker discovery. PLoS One 2010; 5:e15004; PMID:21165148; http://dx.doi.org/10.1371/journal.pone.0015004
108. Davies DR, Gelinas AD, Zhang C, Rohloff JC, Carter JD, O'Connell D, Waugh SM, Wolk SK, Mayfield WS, Burgin AB. Unique motifs and hydrophobic interactions shape the binding of modified DNA ligands to protein targets. Proc Natl Acad Sci 2012; 109:19971-6; PMID:23139410; http://dx.doi.org/10.1073/pnas.1213933109
109. Ochsner UA, Katilius E, Janjic N. Detection of Clostridium difficile toxins A, B and binary toxin with slow off-rate modified aptamers. Diagn Microbiol Infect Dis 2013; 76:278-85; PMID:23680240; http://dx.doi.org/10.1016/j.diagmicrobio.2013.03.029
110. Jhaveri S, Olwin B, Ellington AD. In vitro selection of phosphorothiolated aptamers. Bioorg Med Chem Lett 1998; 8:2285-90; PMID:9873529; http://dx.doi.org/10.1016/S0960-894X(98)00414-4
111. King DJ, Bassett SE, Li X, Fennewald SA, Herzog NK, Luxon BA, Shope R, Gorenstein DG. Combinatorial selection and binding of phosphorothioate aptamers targeting human NF-κB RelA (p65) and p50. Biochemistry 2002; 41:9696-706; PMID:12135392; http://dx.doi.org/10.1021/bi020220k
112. King DJ, Ventura DA, Brasier AR, Gorenstein DG. Novel combinatorial selection of phosphorothioate oligonucleotide aptamers. Biochemistry 1998; 37:16489-93; PMID:9843415; http://dx.doi.org/10.1021/bi981780f
113. Lato SM, Ozerova NDS, He K, Sergueeva Z, Shaw BR, Burke DH. Boron-containing aptamers to ATP. Nucleic Acids Res 2002; 30:1401-7; PMID:11884639; http://dx.doi.org/10.1093/nar/30.6.1401