Cited by 687DNA and Nucleic Acid ChemistryRNA Interference and Gene DeliveryRNA and protein synthesis mechanisms

The DOI matches its Crossref record; 123 of the 123 references it cites were found in a registry or an index.

Phosphorothioates, Essential Components of Therapeutic Oligonucleotides

Eckstein, Fritz·2014·Nucleic Acid Therapeutics

DOI 10.1089/nat.2014.0506

Open this paper in CoChat — free account

Abstract

Phosphorothioates have found their usefulness in the general area of oligonucleotide therapeutic applications. Initially this modification was introduced into the antisense methodology because of the nuclease resistance of the phosphorothioate linkage in comparison with that of the phosphate linkage. However, as experimental data accumulated, it was detected that this chemical modification also facilitates cellular uptake and bioavailibity in vivo. Thus, today the majority of therapeutic oligonucleotides contain this modification. This review will discuss the historical development of this modification and present some of its chemical properties where they differ from those of the phosphate group. The antisense application will be discussed in the original context with cleavage of the target mRNA, but other target RNAs such as microRNAs and long noncoding RNAs will also be covered. It continues with applications where the target RNA should not be cleaved. A brief presentation of decoy oligonucleotides will be included, as well as some miscellaneous applications. Cellular uptake is a crucial step for oligonucleotides to reach their target and will be briefly reviewed. Lastly, a most surprising recent observation is the presence of phosphorothioate groups in bacterial DNA where functions still remain to be fully determined.

Integrity signals

Registry

Crossref · 10.1089/nat.2014.0506

Cites

123 of 123 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Untitled work
Bartel (2004) · doi:10.1016/s0092-8674(04)00045-5 · Cited by 34,714
The nature of the chemical bond—1992
Pauling, L. C. (1992) · Journal of Chemical Education · doi:10.1021/ed069p519 · Cited by 13,235
CpG motifs in bacterial DNA trigger direct B-cell activation
Krieg, A. M., Yi, A.-K., Matson, S., Waldschmidt, T. J., Bishop, G. A., Teasdale, R., Koretzky, G. A., & Klinman, D. M. (1995) · Nature · doi:10.1038/374546a0 · Cited by 3,508
miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting
Esau, C., Davis, S., Murray, S. F., Yu, X. X., Pandey, S. K., Pear, M., Watts, L., Booten, S. L., Graham, M., McKay, R., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.005 · Cited by 2,082
Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide.
Zamecnik, P. C., & Stephenson, M. L. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.1.280 · Cited by 1,792
A Sequencing Method Based on Real-Time Pyrophosphate
Ronaghi, M., Uhlén, M., & Nyrén, P. (1998) · Science · doi:10.1126/science.281.5375.363 · Cited by 1,630
LNA-mediated microRNA silencing in non-human primates
Elmén, J., Lindow, M., Schütz, S., Lawrence, M., Petri, A., Obad, S., Lindholm, M., Hedtjärn, M., Hansen, H. F., Berger, U., et al. (2008) · Nature · doi:10.1038/nature06783 · Cited by 1,589
RNA Targeting Therapeutics: Molecular Mechanisms of Antisense Oligonucleotides as a Therapeutic Platform
Bennett, C. F., & Swayze, E. E. (2010) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105654 · Cited by 1,431
Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution
Ulitsky, I., Shkumatava, A., Jan, C. H., Sive, H. L., & Bartel, D. P. (2011) · Cell · doi:10.1016/j.cell.2011.11.055 · Cited by 1,197
A general two-metal-ion mechanism for catalytic RNA
Steitz, T. A., & Steitz, J. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.14.6498 · Cited by 1,171
RNA therapeutics: beyond RNA interference and antisense oligonucleotides
Kole, R., Krainer, A. R., & Altman, S. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3625 · Cited by 1,152
Acids and Bases: Hard acids prefer to associate with hard bases, and soft acids prefer to associate with soft bases.
Pearson, R. G. (1966) · Science · doi:10.1126/science.151.3707.172 · Cited by 979
Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial
Raal, F. J., Santos, R. D., Blom, D. J., Marais, A. D., Charng, M., Cromwell, W. C., Lachmann, R., Gaudet, D., Tan, J. L., Chasan-Taber, S., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60284-x · Cited by 934
NUCLEOSIDE PHOSPHOROTHIOATES
Eckstein, F. (1985) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.54.070185.002055 · Cited by 849
Self-citation
Evaluation of 2‘-modified oligonucleotides containing 2‘-deoxy gaps as antisense inhibitors of gene expression
Monia, B. P., Lesnik, E. A., Gonzalez, C., Lima, W. F., McGee, D. P. C., Guinosso, C. J., Kawasaki, A. M., Cook, P. D., & Freier, S. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85268-7 · Cited by 779
Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation
Modarresi, F., Faghihi, M. A., López-Toledano, M. A., Fatemi, R. P., Magistri, M., Brothers, S. P., van der Brug, M. P., & Wahlestedt, C. (2012) · Nature Biotechnology · doi:10.1038/nbt.2158 · Cited by 683
Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse modelPreprint
Hua, Y., Sahashi, K., Hung, G., Rigo, F., Passini, M. A., Bennett, C. F., & Krainer, A. R. (2010) · Genes & Development · doi:10.1101/gad.1941310 · Cited by 680
Systemic Administration of PRO051 in Duchenne's Muscular Dystrophy
Goemans, N., Tulinius, M., van den Akker, J. T., Burm, B. E. A., Ekhart, P. F., Heuvelmans, N., Holling, T. M., Janson, A. A. M., Platenburg, G. J., Sipkens, J. A., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1011367 · Cited by 675
Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice
Prakash, T. P., Graham, M., Yu, J., Carty, R., Low, A., Chappell, A., Schmidt, K., Zhao, C., Aghajan, M., Murray, H., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku531 · Cited by 588
A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioningPreprint
Valouev, A., Ichikawa, J. K., Tonthat, T., Stuart, J., Ranade, S., Peckham, H. E., Zeng, K., Malek, J. A., Costa, G. L., McKernan, K. J., et al. (2008) · Genome Research · doi:10.1101/gr.076463.108 · Cited by 580
Phosphorothioate analogs of oligodeoxynucleotides: inhibitors of replication and cytopathic effects of human immunodeficiency virus.
Matsukura, M., Shinozuka, K., Zon, G., Mitsuya, H., Reitz, M. S., Cohen, J. S., & Broder, S. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.21.7706 · Cited by 533
Specificity, duplex degradation and subcellular localization of antagomirs
Krützfeldt, J., Kuwajima, S., Braich, R. S., Rajeev, K. G., Pena, J., Tuschl, T., Manoharan, M., & Stoffel, M. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm024 · Cited by 462
Role of RNase H in hybrid-arrested translation by antisense oligonucleotides.
Walder, R. Y., & Walder, J. A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.14.5011 · Cited by 453
Regulation of Gene Expression with Double-Stranded Phosphorothioate Oligonucleotides
Bielinska, A. U., Shivdasani, R. A., Zhang, L., & Nabel, G. J. (1990) · Science · doi:10.1126/science.2237444 · Cited by 372
Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents
Stein, C. A., Hansen, J. B., Lai, J., Wu, S., Voskresenskiy, A., H⊘g, A., Worm, J., Hedtjärn, M., Souleimanian, N., Miller, P., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp841 · Cited by 360
RNA catalyses nuclear pre-mRNA splicing
Fica, S. M., Tuttle, N., Novak, T., Li, N., Lu, J., Koodathingal, P., Dai, Q., Staley, J. P., & Piccirilli, J. A. (2013) · Nature · doi:10.1038/nature12734 · Cited by 348
A semisynthetic epitope for kinase substrates
Allen, J. J., Li, M., Brinkworth, C. S., Paulson, J., Wang, D., Hübner, A., Chou, W.-H., Davis, R. J., Burlingame, A. L., Messing, R. O., et al. (2007) · Nature Methods · doi:10.1038/nmeth1048 · Cited by 330
MODIFIED OLIGONUCLEOTIDES: Synthesis and Strategy for Users
Verma, S. K., & Eckstein, F. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.99 · Cited by 315
Self-citation
Stability constants of magnesium and cadmium complexes of adenine nucleotides and thionucleotides and rate constants for formation and dissociation of magnesium-ATP and magnesium-ADP
Pecoraro, V. L., Hermes, J. D., & Cleland, W. W. (1984) · Biochemistry · doi:10.1021/bi00317a026 · Cited by 291
Oligodeoxynucleoside phosphoramidates and phosphorothioates as inhibitors of human immunodeficiency virus.
Agrawal, S., Goodchild, J., Civeira, M. P., Thornton, A., Sarin, P. S., & Zamecnik, P. C. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.19.7079 · Cited by 291
Pharmacokinetic Properties of 2′-O-(2-Methoxyethyl)-Modified Oligonucleotide Analogs in Rats
Geary, R. S., Watanabe, T. A., Truong, L., Freier, S., Lesnik, E. A., Sioufi, N. B., Sasmor, H. M., Manoharan, M., & Levin, A. A. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38831-7 · Cited by 289
Bond Order and Charge Localization in Nucleoside Phosphorothioates
Frey, P. A., & Sammons, R. D. (1985) · Science · doi:10.1126/science.2984773 · Cited by 281
Mechanisms of single-stranded phosphorothioate modified antisense oligonucleotide accumulation in hepatocytes
Koller, E., Vincent, T. M., Chappell, A., De, S., Manoharan, M., & Bennett, C. F. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr089 · Cited by 281
Automated solid-phase synthesis, separation, and stereochemistry of phosphorothioate analogs of oligodeoxyribonucleotides
Stec, W. J., Zon, G., & Egan, W. (1984) · Journal of the American Chemical Society · doi:10.1021/ja00332a054 · Cited by 278
Single-Stranded RNAs Use RNAi to Potently and Allele-Selectively Inhibit Mutant Huntingtin Expression
Yu, D., Pendergraff, H. M., Liu, J., Kordasiewicz, H. B., Cleveland, D. W., Swayze, E. E., Lima, W. F., Crooke, S. T., Prakash, T. P., & Corey, D. R. (2012) · Cell · doi:10.1016/j.cell.2012.08.002 · Cited by 277
The Role of Environmental Carcinogens, Viruses, and Genetic
Powers, A. A., & Carbone, M. (2002) · Cancer Biology & Therapy · doi:10.4161/cbt.1.4.4 · Cited by 276
Phosphorothioation of DNA in bacteria by dnd genes
Wang, L., Chen, S., Xu, T., Taghizadeh, K., Wishnok, J. S., Zhou, X., You, D., Deng, Z., & Dedon, P. C. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.39 · Cited by 274
Regulation of viral expression of human immunodeficiency virus in vitro by an antisense phosphorothioate oligodeoxynucleotide against rev (art/trs) in chronically infected cells.
Matsukura, M., Zon, G., Shinozuka, K., Robert-Guroff, M., Shimada, T., Stein, C. A., Mitsuya, H., Wong‐Staal, F., Cohen, J. S., & Broder, S. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.11.4244 · Cited by 263
Single-Stranded siRNAs Activate RNAi in Animals
Lima, W. F., Prakash, T. P., Murray, H. M., Kinberger, G. A., Li, W., Chappell, A. E., Li, C., Murray, S., Gaus, H. J., Seth, P. P., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.014 · Cited by 260
The use of phosphorothioate-modified DNA in restriction enzyme reactions to prepare nicked DNA
Taylor, J. W., SCHMIDT, W. A., Cosstick, R., Okruszek, A., & Eckstein, F. (1985) · Nucleic Acids Research · doi:10.1093/nar/13.24.8749 · Cited by 245
Self-citation
Fomivirsen
Perry, C. M., & Balfour, J. A. B. (1999) · Drugs · doi:10.2165/00003495-199957030-00010 · Cited by 243
DNA and RNA Sequence Determination Based on Phosphorothioate Chemistry
Gish, G. D., & Eckstein, F. (1988) · Science · doi:10.1126/science.2453926 · Cited by 232
Self-citation
Synthesis, Properties, and Applications of Oligonucleotides Containing an RNA Dinucleotide Phosphorothiolate Linkage
Li, N., Frederiksen, J. K., & Piccirilli, J. A. (2011) · Accounts of Chemical Research · doi:10.1021/ar200131t · Cited by 225
Structural principles for the inhibition of the 3′-5′ exonuclease activity of Escherichia coli DNA polymerase I by phosphorothioates
Brautigam, C. A., & Steitz, T. A. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1586 · Cited by 205
Adenosine 5′-0(3-thiotriphosphate) in the control of phosphorytase activity
Gratecos, D., & Fischer, E. H. (1974) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(74)80237-8 · Cited by 190
CpG Still Rocks! Update on an Accidental Drug
Krieg, A. Μ. (2012) · Nucleic Acid Therapeutics · doi:10.1089/nat.2012.0340 · Cited by 184
Thiophosphate analogs of nucleoside di- and triphosphates
Goody, R. S., & Eckstein, F. (1971) · Journal of the American Chemical Society · doi:10.1021/ja00752a042 · Cited by 181
Self-citation
Antisense Drug Technology
(2007) · CRC Press eBooks · doi:10.1201/9780849387951 · Cited by 181
RNase H cleavage of RNA hybridized to oligonucleotides containing methylphosphonate, phosphorothioate and phosphodiester bonds
Furdon, P. J., Domiński, Z., & Kole, R. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.22.9193 · Cited by 178
A study of the mechanism of DNA polymerase I from Escherichia coli with diastereomeric phosphorothioate analogs of deoxyadenosine triphosphate.
Burgers, P., & Eckstein, F. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50258-1 · Cited by 176
Self-citation
Mapping the active site of ribonuclease P RNA using a substrate containing a photoaffinity agent.
Burgin, A. B., & Pace, N. R. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07633.x · Cited by 175
Absolute configuration of the diastereomers of adenosine 5'-O-(1-thiotriphosphate): consequences for the stereochemistry of polymerization by DNA-dependent RNA polymerase from Escherichia coli.
Burgers, P., & Eckstein, F. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.10.4798 · Cited by 169
Self-citation
Synthesis and configurational analysis of a dinucleoside phosphate isotopically chiral at phosphorus. Stereochemical course of Penicillium citrinum nuclease P1 reaction
Potter, B. V. L., Connolly, B. A., & Eckstein, F. (1983) · Biochemistry · doi:10.1021/bi00275a008 · Cited by 166
Self-citation
Synthesis and characterization of an octanucleotide containing the EcoRI recognition sequence with a phosphorothioate group at the cleavage site
Connolly, B. A., Potter, B. V. L., Eckstein, F., Pingoud, A. M., & Grotjahn, L. (1984) · Biochemistry · doi:10.1021/bi00310a010 · Cited by 159
Self-citation
Divalent cation-dependent stereospecificity of adenosine 5‘-O-(2-thiotriphosphate) in the hexokinase and pyruvate kinase reactions. The absolute stereochemistry of the diastereoisomers of adenosine 5‘-O-(2-thiotriphosphate).
Jaffe, E. K., & Cohn, M. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34617-3 · Cited by 149
Inhibition of deoxyribonucleases by phosphorothioate groups in oligodeoxyribonucleotides
Spitzer, S. G., & Eckstein, F. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.24.11691 · Cited by 143
Self-citation
Geometry of the First Step in the Action of Ribonuclease-A
Usher, D. A., Erenrich, E. S., & Eckstein, F. (1972) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.69.1.115 · Cited by 140
Self-citation
Interferon Induction Increased through Chemical Modification of a Synthetic Polyribonucleotide
Clercq, E. D., Eckstein, F., & Merigan, T. C. (1969) · Science · doi:10.1126/science.165.3898.1137 · Cited by 135
Self-citation
Cellular Uptake and Intracellular Trafficking of Oligonucleotides: Implications for Oligonucleotide Pharmacology
Juliano, R. L., Ming, X., Carver, K. A., & Laing, B. M. (2014) · Nucleic Acid Therapeutics · doi:10.1089/nat.2013.0463 · Cited by 135
A novel host-specific restriction system associated with DNA backbone S-modification in Salmonella
Xu, T., Yao, F., Zhou, X., Deng, Z., & You, D. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq610 · Cited by 134
Absolute Stereochemistry of the Second Step of Ribonuclease Action
Usher, D. A., Richardson, D. I., & Eckstein, F. (1970) · Nature · doi:10.1038/228663a0 · Cited by 132
Self-citation
Stereospecificity of nucleases towards phosphorothioate-substituted RNA: stereochemistry of transcription by T7 RNA polymerase
Griffiths, A. D., POTTER, B. V. L., & Eperon, I. C. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.10.4145 · Cited by 127
Characterization of Target mRNA Reduction Through In Situ RNA Hybridization in Multiple Organ Systems Following Systemic Antisense Treatment in Animals
Hung, G., Xiao, X., Peralta, R. Q., Bhattacharjee, G., Murray, S., Norris, D., Guo, S., & Monia, B. P. (2013) · Nucleic Acid Therapeutics · doi:10.1089/nat.2013.0443 · Cited by 126
Solid-Phase Synthesis of Stereoregular Oligodeoxyribonucleoside Phosphorothioates Using Bicyclic Oxazaphospholidine Derivatives as Monomer Units
Oka, N., Yamamoto, M., Sato, T., & Wada, T. (2008) · Journal of the American Chemical Society · doi:10.1021/ja805780u · Cited by 123
Chiral phosphorothioate analogues of B-DNA
Cruse, W. B. T., Salisbury, S. A., Brown, T., Cosstick, R., Eckstein, F., & Kennard, O. (1986) · Journal of Molecular Biology · doi:10.1016/0022-2836(86)90035-5 · Cited by 123
Self-citation
Deoxyribonucleoside 3‘- O -(2-Thio- and 2-Oxo-“spiro”-4,4-pentamethylene-1,3,2-oxathiaphospholane)s: Monomers for Stereocontrolled Synthesis of Oligo(deoxyribonucleoside phosphorothioate)s and Chimeric PS/PO Oligonucleotides
Stec, W. J., Karwowski, B. T., Boczkowska, M., Guga, P., Koziołkiewicz, M., Sochacki, M., Wieczorek, M. W., & Błaszczyk, J. (1998) · Journal of the American Chemical Society · doi:10.1021/ja973801j · Cited by 122
Phosphorothioate primers improve the amplification of DNA sequences by DNA polymerases with proofreading activity
Skerra, A. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.14.3551 · Cited by 118
Nucleoside Phosphorothioates
Eckstein, F. (1966) · Journal of the American Chemical Society · doi:10.1021/ja00970a054 · Cited by 116
Self-citation
Stereodifferentiation—the effect of P chirality of oligo (nucleoside phosphorothioates) on the activity of bacterial RNase H
Koziołkiewicz, M., Krakowiak, A., Kwinkowski, M., Boczkowska, M., & Stec, W. J. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.24.5000 · Cited by 111
Chemical Modification Study of Antisense Gapmers
Stanton, R. V., Sciabola, S., Salatto, C. T., Weng, Y., Moshinsky, D., Little, J., Walters, E., Kreeger, J. M., DiMattia, D. A., Chen, T. X., et al. (2012) · Nucleic Acid Therapeutics · doi:10.1089/nat.2012.0366 · Cited by 110
Genomic mapping of phosphorothioates reveals partial modification of short consensus sequences
Cao, B., Chen, C., DeMott, M. S., Cheng, Q., Clark, T. A., Xiong, X., Zheng, X., Butty, V. L., Levine, S. S., Yuan, G., et al. (2014) · Nature Communications · doi:10.1038/ncomms4951 · Cited by 107
TLR9-mediated siRNA delivery for targeting of normal and malignant human hematopoietic cells in vivo
Zhang, Q., Hossain, D. M. S., Nechaev, S., Kozłowska, A. K., Zhang, W., Liu, Y., Kowolik, C. M., Swiderski, P. M., Rossi, J. J., Forman, S. J., et al. (2013) · Blood · doi:10.1182/blood-2012-07-442590 · Cited by 107
Defining the chemical groups essential for Tetrahymena group I intron function by nucleotide analog interference mapping
Strobel, S. A., & Shetty, K. D. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.7.2903 · Cited by 107
Synthetic oligonucleotides recruit ILF2/3 to RNA transcripts to modulate splicing
Rigo, F., Hua, Y., Chun, S. J., Prakash, T. P., Krainer, A. R., & Bennett, C. F. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.939 · Cited by 104
A Chemical View of Oligonucleotides for Exon Skipping and Related Drug Applications
Järver, P., O’Donovan, L., & Gait, M. J. (2013) · Nucleic Acid Therapeutics · doi:10.1089/nat.2013.0454 · Cited by 102
Deoxynucleoside [1-thio]triphosphates prevent proofreading during in vitro DNA synthesis.
Kunkel, T. A., Eckstein, F., Mildvan, A. S., Koplitz, R. M., & Loeb, L. A. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.11.6734 · Cited by 102
Self-citation
Stereochemistry of a substrate for pancreatic ribonuclease. Crystal and molecular structure of the triethylammonium salt of uridine 2', 3'-0,0-cyclophosphorothioate
Saenger, W., & Eckstein, F. (1970) · Journal of the American Chemical Society · doi:10.1021/ja00718a038 · Cited by 98
Self-citation
Movement of the Guide Sequence During RNA Catalysis by a Group I Ribozyme
Wang, J., Downs, W. D., & Cech, T. R. (1993) · Science · doi:10.1126/science.7682726 · Cited by 97
Antisense Oligonucleotides for the Treatment of Spinal Muscular Atrophy
Porensky, P. N., & Burghes, A. H. M. (2013) · Human Gene Therapy · doi:10.1089/hum.2012.225 · Cited by 89
Stereodefined Phosphorothioate Analogues of DNA: Relative Thermodynamic Stability of the Model PS-DNA/DNA and PS-DNA/RNA Complexes
Boczkowska, M., Guga, P., & Stec, W. J. (2002) · Biochemistry · doi:10.1021/bi026225z · Cited by 88
A study of the mechanism of T4 DNA polymerase with diastereomeric phosphorothioate analogues of deoxyadenosine triphosphate.
Romaniuk, P. J., & Eckstein, F. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34435-1 · Cited by 86
Self-citation
Phosphorothioate DNA as an antioxidant in bacteria
Xie, X., Liang, J., Pu, T., Xu, F., Yao, F., Yang, Y., Zhao, Y., You, D., Zhou, X., Deng, Z., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks650 · Cited by 81
Direct sequencing of polymerase chain reaction amplified DNA fragments through the incorporation of deoxynucleoside α-thiotriphosphates
Nakamaye, K. L., Gish, G. D., Eckstein, F., & Vosberg, H.-P. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.21.9947 · Cited by 79
Self-citation
Antisense 2′-Deoxy, 2′-Fluoroarabino Nucleic Acid (2′F-ANA) Oligonucleotides: In Vitro Gymnotic Silencers of Gene Expression Whose Potency Is Enhanced by Fatty Acids
Souleimanian, N. E., Deleavey, G. F., Soifer, H. S., Wang, S., Tiemann, K., Damha, M. J., & Stein, C. A. (2012) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2012.35 · Cited by 71
Development of Therapeutic Splice-Switching Oligonucleotides
Disterer, P., Kryczka, A., Liu, Y., Badi, Y. E., Wong, J. J., Owen, J. S., & Khoo, B. C. E. (2014) · Human Gene Therapy · doi:10.1089/hum.2013.234 · Cited by 71
Potent Gene-Specific Inhibitory Properties of Mixed-Backbone Antisense Oligonucleotides Comprised of 2‘-Deoxy-2‘-fluoro- d -arabinose and 2‘-Deoxyribose Nucleotides,
Lok, C., Viazovkina, E., Min, K., Nagy, E., Wilds, C. J., Damha, M. J., & Parniak, M. A. (2002) · Biochemistry · doi:10.1021/bi0115075 · Cited by 70
Design, synthesis and biological evaluation of novel antagonist compounds of Toll-like receptors 7, 8 and 9
Kandimalla, E. R., Bhagat, L., Wang, D., Yu, D. S., Sullivan, T., Monica, N. L., & Agrawal, S. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt078 · Cited by 69
Oligonucleotide N3′→P5′ Phosphoramidates and Thio‐Phoshoramidates as Potential Therapeutic Agents
Gryaznov, S. M. (2010) · Chemistry & Biodiversity · doi:10.1002/cbdv.200900187 · Cited by 68
Synthesis of dinucleoside monophosphorothioates via addition of sulphur to phosphite triesters.
Burgers, P., & Eckstein, F. (1978) · Tetrahedron Letters · doi:10.1016/s0040-4039(01)95072-5 · Cited by 62
Self-citation
Fluorescent labelling of tRNA and oligodeoxynucleotides using T4 RNA ligase
Cosstick, R., McLaughlin, L. W., & Eckstein, F. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.4.1791 · Cited by 61
Self-citation
Impaired Transition State Complementarity in the Hydrolysis of O-Arylphosphorothioates by Protein-Tyrosine Phosphatases
Zhang, Y., Hollfelder, F., Gordon, S. J., Chen, L., Keng, Y., Wu, L., Herschlag, D., & Zhang, Z. (1999) · Biochemistry · doi:10.1021/bi990836i · Cited by 59
Peptide Conjugation of 2′- O -methyl Phosphorothioate Antisense Oligonucleotides Enhances Cardiac Uptake and Exon Skipping in mdx Mice
Jirka, S. M. G., Heemskerk, H., Winter, C. L. T.-D., Muilwijk, D., Pang, K. H., de Visser, P. C., Janson, A. A. M., Karnaoukh, T. G., Vermue, R., Hoen, P. A. C. ’., et al. (2013) · Nucleic Acid Therapeutics · doi:10.1089/nat.2013.0448 · Cited by 59
Stereochemical course of polymerization catalyzed by avian myeloblastosis virus reverse transcriptase.
Bartlett, P. A., & Eckstein, F. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34212-1 · Cited by 59
Self-citation
The antiviral activity of thiophosphate-substituted polyribonucleotides in vitro and in vivo
Clercq, E. D., Eckstein, F., Sternbach, H., & Merigan, T. C. (1970) · Virology · doi:10.1016/0042-6822(70)90285-0 · Cited by 57
Self-citation
Sulfur does not form double bonds in phosphorothioate anions
Liang, C., & Allen, L. C. (1987) · Journal of the American Chemical Society · doi:10.1021/ja00255a034 · Cited by 55
Stereochemical course of DNA hydrolysis by nuclease S1.
Potter, B. V. L., Romaniuk, P. J., & Eckstein, F. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)33051-5 · Cited by 54
Self-citation
Phosphorothioate-containing RNAs show mRNA activity in the prokaryotic translation systemsin vitro
Ueda, T., Tohda, H., Chikazumi, N., Eckstein, F., & Watanabe, K. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.3.547 · Cited by 52
Self-citation
P-Chirality-Dependent Immune Activation by Phosphorothioate CpG Oligodeoxynucleotides
Krieg, A. Μ., Guga, P., & Stec, W. J. (2003) · Oligonucleotides · doi:10.1089/154545703322860807 · Cited by 51
Pathological phenotypes and in vivo DNA cleavage by unrestrained activity of a phosphorothioate‐based restriction system in S almonella
Cao, B., Cheng, Q., Gu, C., Yao, F., DeMott, M. S., Zheng, X., Deng, Z., Dedon, P. C., & You, D. (2014) · Molecular Microbiology · doi:10.1111/mmi.12692 · Cited by 49
Stereodependent Inhibition of Plasminogen Activator Inhibitor Type 1 by Phosphorothioate Oligonucleotides: Proof of Sequence Specificity in Cell Culture and In Vivo Rat Experiments
Stec, W. J., Cierniewski, C. S., Okruszek, A., Kobylańska, A., Pawłowska, Z., Koziołkiewicz, M., Pluskota, E., Maciaszek, A. D., Rębowska, B., & Stasiak, M. (1997) · Antisense and Nucleic Acid Drug Development · doi:10.1089/oli.1.1997.7.567 · Cited by 45
ss-siRNAs allele selectively inhibit ataxin-3 expression: multiple mechanisms for an alternative gene silencing strategy
Liu, J., Yu, D., Aiba, Y., Pendergraff, H. M., Swayze, E. E., Lima, W. F., Hu, J., Prakash, T. P., & Corey, D. R. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt693 · Cited by 42
Acceptor Helix Interactions in a Class II tRNA Synthetase: Photoaffinity Crosslinking of an RNA Miniduplex Substrate
Musier‐Forsyth, K., & SCHIMMEL, P. R. (1994) · Biochemistry · doi:10.1021/bi00169a019 · Cited by 42
A Polyribonucleotide Containing Alternating → P = O and → P = S Linkages
Matzura, H., & Eckstein, F. (1968) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1967.tb19551.x · Cited by 41
Self-citation
Metal-ion rescue revisited: Biochemical detection of site-bound metal ions important for RNA folding
Frederiksen, J. K., Li, N., Das, R., Herschlag, D., & Piccirilli, J. A. (2012) · RNA · doi:10.1261/rna.028738.111 · Cited by 40
Incorporation of phosphorothioate groups into fd and φX174 DNA
Vosberg, H.-P., & Eckstein, F. (1977) · Biochemistry · doi:10.1021/bi00635a020 · Cited by 38
Self-citation
Allele-Selective Inhibition of Mutant Atrophin-1 Expression by Duplex and Single-Stranded RNAs
Hu, J., Liu, J., Jayaprakash, K. N., Lackey, J. G., Kuchimanchi, S., Rajeev, K. G., Manoharan, M., Swayze, E. E., Lima, W. F., Prakash, T. P., et al. (2014) · Biochemistry · doi:10.1021/bi500610r · Cited by 35
Target mRNA inhibition by oligonucleotide drugs in man
Lightfoot, H. L., & Hall, J. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks861 · Cited by 34
Effect of ion pairing on bond order and charge localization in alkyl phosphorothioates
Baraniak, J., & Frey, P. A. (1988) · Journal of the American Chemical Society · doi:10.1021/ja00220a067 · Cited by 34
Uridin‐2′.3′‐O.O‐cyclothiophosphat
Eckstein, F., & Gindl, H. (1968) · Chemische Berichte · doi:10.1002/cber.19681010518 · Cited by 33
Self-citation
Fomiversen Sodium Approved to Treat CMV Retinitis
Piascik, P. (1999) · Journal of the American Pharmaceutical Association (1996) · doi:10.1016/s1086-5802(16)30428-4 · Cited by 32
Phosphorus-oxygen bond order in adenosine 5'-O-phosphorothioate dianion
Iyengar, R., Eckstein, F., & Frey, P. A. (1984) · Journal of the American Chemical Society · doi:10.1021/ja00338a059 · Cited by 31
Self-citation
Thiol-ene Enabled Detection of Thiophosphorylated Kinase Substrates
Garber, K. C. A., & Carlson, E. E. (2013) · ACS Chemical Biology · doi:10.1021/cb400184v · Cited by 27
Thiophosphorylated Substrate Analogs Are Potent Active Site-Directed Inhibitors of Protein-Tyrosine Phosphatases
Hiriyanna, K. T., Baedke, D. S., Baek, K., Forney, B. A., Kordiyak, G. J., & Ingebritsen, T. S. (1994) · Analytical Biochemistry · doi:10.1006/abio.1994.1545 · Cited by 26
Polyribonucleotides containing a thiophosphate backbone
Eckstein, F., & Gindl, H. (1969) · FEBS Letters · doi:10.1016/0014-5793(69)80037-2 · Cited by 26
Self-citation
Modification of Decoy Oligodeoxynucleotides to Achieve the Stability and Therapeutic Efficacy
Osako, M. K., Hironori Nakagami, A., & Morishita, R. (2012) · Current Topics in Medicinal Chemistry · doi:10.2174/156802612803531397 · Cited by 25
Stereochemistry of the transesterification step of pancreatic ribonuclease
Eckstein, F., Saenger, W., & Suck, D. (1972) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(72)80235-3 · Cited by 25
Self-citation
Kinase Assay Based on Thiophosphorylation and Biotinylation
Jeong, S., & Nikiforov, T. T. (1999) · BioTechniques · doi:10.2144/99276rr01 · Cited by 23
Site-Specific Derivatization of RNA with Photocrosslinkable Groups
Konarska, M. M. (1999) · Methods · doi:10.1006/meth.1999.0753 · Cited by 22
Decoy oligodeoxynucleotide against STAT transcription factors decreases allergic inflammation in a rat asthma model
Lührmann, A., Tschernig, T., von der Leyen, H. E., Hecker, M., Pabst, R., & Wagner, A. H. (2010) · Experimental Lung Research · doi:10.3109/01902140903144138 · Cited by 22
Exploring the Effect of Sequence Length and Composition on Allele-Selective Inhibition of Human Huntingtin Expression by Single-Stranded Silencing RNAs
Hu, J., Liu, J., Yu, D., Aiba, Y., Lee, S., Pendergraff, H. M., Boubaker-Vitre, J., Artates, J. W., Lagier‐Tourenne, C., Lima, W. F., et al. (2014) · Nucleic Acid Therapeutics · doi:10.1089/nat.2013.0476 · Cited by 22
Synthesis, Properties and Application of Nucleic Acids Containing Phosphorothiolate Linkages
Cosstick, R., & Gaynor, J. W. (2008) · Current Organic Chemistry · doi:10.2174/138527208783743769 · Cited by 20
Inhibition of restriction endonuclease hydrolysis by phosphorothioate-containing DNA
Sayers, J. R., Olsen, D. B., & Eckstein, F. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.22.9495 · Cited by 19
Self-citation
Antisense-Mediated Exon Skipping: Networking to Meet Opportunities and to Overcome Challenges
Aartsma-Rus, A. M. (2014) · Nucleic Acid Therapeutics · doi:10.1089/nat.2014.1500 · Cited by 17

Flagged first, then by citations

Research works printed but not linked: 5

Dias N, and Stein CA. (2002) Antisense oligonucleotides: Basic concepts and mechanisms. Mol Cancer Ther, 1:347–355.
Juliano RL. (2005). Peptide-oligonucleotide conjugatesfor the delivery of antisense and siRNA. Curr Opin Mel Ther, 7:132–136.
Manoharan M. (2013). RNAi therapeutics using GalNAc-siRNA conjugate delivery platform: New era of oligonucleotides. Presented at Oligonucleotide Therapeutics Society Ninth Annual Meeting, Naples, Italy, October 6–8, 2013.
Bhat B, , Neben S, , Tay J, , Liu K, , Chau N, , Hogan D, , MacKenna D, , Gibson N. (2014). RG-101, a GalNAC-conjugated anti-miR employing a unique mechanism of action by targeting host factor microRNA-122 (miR-122), demonstrates potent activity and reduction of HCV in preclinical studies. Hepatology, 58:1377A–1395A.
Hutchinson CAIII, , Smith HO, , Pfannkoch C, and Venter JC. (2005). Cell-free cloning using φ29 DNA polymerase. Proc Natl Acad Sci (USA), 102:17322–17336.

Sorted by citations

Advances in oligonucleotide drug delivery
Roberts, T. C., Langer, R., & Wood, M. J. A. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0075-7 · Cited by 2,121
The evolution of commercial drug delivery technologies
Vargason, A. M., Anselmo, A. C., & Mitragotri, S. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00698-w · Cited by 1,361
The chemical evolution of oligonucleotide therapies of clinical utility
Khvorova, A., & Watts, J. K. (2017) · Nature Biotechnology · doi:10.1038/nbt.3765 · Cited by 1,216
Overcoming cellular barriers for RNA therapeutics
Dowdy, S. F. (2017) · Nature Biotechnology · doi:10.1038/nbt.3802 · Cited by 1,139
Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells
Hendel, A., Bak, R. O., Clark, J. T., Kennedy, A. B., Ryan, D. E., Roy, S., Steinfeld, I., Lunstad, B. D., Kaiser, R. J., Wilkens, A. B., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3290 · Cited by 1,090

See all 687

Authors: Eckstein, F.
Affiliations: Max Planck Society (DE)
Corresponding author: Eckstein, Fritz
Venue: Nucleic Acid Therapeutics
Publisher: SAGE Publications
Published: 2014-12
Volume: 24
Issue: 6
Pages: 374-387
ISSN: 2159-3337 (ISSN-L)
2159-3345
DOI: 10.1089/nat.2014.0506
OpenAlex: W2316132657
Cited by: 684
References: 123
Citations by year: 2026: 69 · 2025: 87 · 2024: 86 · 2023: 75 · 2022: 81 · 2021: 69 · 2020: 64 · 2019: 49 · 2018: 39 · 2017: 25 · 2016: 20 · 2015: 20
FWCI: 2.04
Type: journal article
Language: en
Open access: closed
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Nucleic Acid Therapeutics (publishedVersion)
PubMed (publishedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords: phosphorothioate, oligonucleotide therapeutics, antisense oligonucleotides, nuclease resistance, cellular uptake, bioavailability, microRNA targeting, long non-coding RNA, decoy oligonucleotides, bacterial DNA
MeSH terms: Animals, Humans, Protein Binding, Rabbits, Transcription Factors, Oligonucleotides, Antisense, History, 20th Century, Mice, Phosphorothioate Oligonucleotides

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Phosphorothioates, Essential Components of Therapeutic Oligonucleotides

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks