2'-O-[2-[(N,N-dimethylamino)oxy]ethyl]-modified oligonucleotides inhibit expression of mRNA in vitro and in vivo.

Abstract:

:Synthesis and antisense activity of oligonucleotides modified with 2'-O-[2-[(N,N-dimethylamino)oxy] ethyl] (2'-O-DMAOE) are described. The 2'-O-DMAOE-modified oligonucleotides showed superior metabolic stability in mice. The phosphorothioate oligonucleotide 'gapmers', with 2'-O-DMAOE- modified nucleoside residues at the ends and 2'-deoxy nucleosides residues in the central region, showed dose-dependent inhibition of mRNA expression in cell culture for two targets. 'Gapmer' oligonucleotides have one or two 2'-O-modified regions and a 2'-deoxyoligonucleotide phosphorothioate region that allows RNase H digestion of target mRNA. To determine the in vivo potency and efficacy, BalbC mice were treated with 2'-O-DMAOE gapmers and a dose-dependent reduction in the targeted C-raf mRNA expression was observed. Oligonucleotides with 2'-O-DMAOE modifications throughout the sequences reduced the intercellular adhesion molecule-1 (ICAM-1) protein expression very efficiently in HUVEC cells with an IC(50) of 1.8 nM. The inhibition of ICAM-1 protein expression by these uniformly modified 2'-O-DMAOE oligonucleotides may be due to selective interference with the formation of the translational initiation complex. These results demonstrate that 2'-O-DMAOE- modified oligonucleotides are useful for antisense-based therapeutics when either RNase H-dependent or RNase H-independent target reduction mechanisms are employed.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Prakash TP,Johnston JF,Graham MJ,Condon TP,Manoharan M

doi

10.1093/nar/gkh220

keywords:

subject

Has Abstract

pub_date

2004-02-03 00:00:00

pages

828-33

issue

2

eissn

0305-1048

issn

1362-4962

pii

32/2/828

journal_volume

32

pub_type

杂志文章
  • The TGGCA protein binds to the MMTV-LTR, the adenovirus origin of replication, and the BK virus enhancer.

    abstract::TGGCA-binding proteins are nuclear proteins with high affinity for double-stranded DNA homologous to the prototype recognition sequence 5'YTGGCANNNTGCCAR 3'. Their ubiquitous tissue distribution in higher vertebrates characterizes them as a class of highly conserved proteins which may exert a basic function. To obtain...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/13.6.2045

    authors: Nowock J,Borgmeyer U,Püschel AW,Rupp RA,Sippel AE

    更新日期:1985-03-25 00:00:00

  • RNApredator: fast accessibility-based prediction of sRNA targets.

    abstract::Bacterial genomes encode a plethora of small RNAs (sRNAs), which are heterogeneous in size, structure and function. Most sRNAs act as post-transcriptional regulators by means of specific base pairing interactions with the 5'-untranslated region of mRNA transcripts, thereby modifying the stability of the target transcr...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr467

    authors: Eggenhofer F,Tafer H,Stadler PF,Hofacker IL

    更新日期:2011-07-01 00:00:00

  • The Plant Ontology Database: a community resource for plant structure and developmental stages controlled vocabulary and annotations.

    abstract::The Plant Ontology Consortium (POC, http://www.plantontology.org) is a collaborative effort among model plant genome databases and plant researchers that aims to create, maintain and facilitate the use of a controlled vocabulary (ontology) for plants. The ontology allows users to ascribe attributes of plant structure ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkm908

    authors: Avraham S,Tung CW,Ilic K,Jaiswal P,Kellogg EA,McCouch S,Pujar A,Reiser L,Rhee SY,Sachs MM,Schaeffer M,Stein L,Stevens P,Vincent L,Zapata F,Ware D

    更新日期:2008-01-01 00:00:00

  • Synthesis, structure and thermodynamic properties of 8-methylguanine-containing oligonucleotides: Z-DNA under physiological salt conditions.

    abstract::Various oligonucleotides containing 8-methylguanine (m8G) have been synthesized and their structures and thermodynamic properties investigated. Introduction Of M8G into DNA sequences markedly stabilizes the Z conformation under low salt conditions. The hexamer d(CGC[M8G]CG)2 exhibits a CD spectrum characteristic of th...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/24.7.1272

    authors: Sugiyama H,Kawai K,Matsunaga A,Fujimoto K,Saito I,Robinson H,Wang AH

    更新日期:1996-04-01 00:00:00

  • Heat effects on DNA repair after ionising radiation: hyperthermia commonly increases the number of non-repaired double-strand breaks and structural rearrangements.

    abstract::After ionising radiation double-strand breaks (dsb) are lethal if not repaired or misrepaired. Cell killing is greatly enhanced by hyperthermia and it is questioned here whether heat not only affects dsb repair capacity but also fidelity in a chromosomal context. dsb repair experiments were designed so as to mainly sc...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/29.9.1960

    authors: El-Awady RA,Dikomey E,Dahm-Daphi J

    更新日期:2001-05-01 00:00:00

  • M-Coffee: combining multiple sequence alignment methods with T-Coffee.

    abstract::We introduce M-Coffee, a meta-method for assembling multiple sequence alignments (MSA) by combining the output of several individual methods into one single MSA. M-Coffee is an extension of T-Coffee and uses consistency to estimate a consensus alignment. We show that the procedure is robust to variations in the choice...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkl091

    authors: Wallace IM,O'Sullivan O,Higgins DG,Notredame C

    更新日期:2006-03-23 00:00:00

  • Role of an upstream open reading frame in the translation of polycistronic mRNAs in plant cells.

    abstract::The influence of an upstream small open reading frame (URF) on the translation of two consecutive coding regions on an eukaryotic mRNA was studied. The cis effects of leader length, URF length, the sequences of the URF and neighboring regions, and the trans effects of the Cauliflower mosaic virus transactivator (TAV) ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/20.15.3851

    authors: Fütterer J,Hohn T

    更新日期:1992-08-11 00:00:00

  • Protection of DNA sequences by triplex-bridge formation.

    abstract::We have demonstrated that the DNA sequence between two triplex-forming polypurine.polypyrimidine (Pu.Py) tracts was protected from DNA modifying enzymes upon formation of triplex DNA structures with an oligodeoxyribonucleotide in which two triplex-forming Pu or Py tracts were placed at the termini (triplex-bridge form...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/23.3.452

    authors: Kiyama R,Oishi M

    更新日期:1995-02-11 00:00:00

  • A plant scaffold attached region detected close to a T-DNA integration site is active in mammalian cells.

    abstract::Integration of foreign genes into plant genomes by the Agrobacterium T-DNA transfer system has been considered to occur at random. It has been speculated that the chromosomal structure of the integration site might affect the expression pattern of the introduced genes. To gain insight into the molecular structure of T...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/22.14.2744

    authors: Dietz A,Kay V,Schlake T,Landsmann J,Bode J

    更新日期:1994-07-25 00:00:00

  • Invariant amino acids essential for decoding function of polypeptide release factor eRF1.

    abstract::In eukaryotic ribosome, the N domain of polypeptide release factor eRF1 is involved in decoding stop signals in mRNAs. However, structure of the decoding site remains obscure. Here, we specifically altered the stop codon recognition pattern of human eRF1 by point mutagenesis of the invariant Glu55 and Tyr125 residues ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gki927

    authors: Kolosov P,Frolova L,Seit-Nebi A,Dubovaya V,Kononenko A,Oparina N,Justesen J,Efimov A,Kisselev L

    更新日期:2005-11-10 00:00:00

  • A novel suicide substrate for DNA topoisomerases and site-specific recombinases.

    abstract::DNA topoisomerases and DNA site-specific recombinases are biologically important enzymes involved in a diverse set of cellular processes. We show that replacement of a phosphodiester linkage by a 5'-bridging phosphorothioate linkage creates an efficient suicide substrate for calf thymus topoisomerase I and lambda inte...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/23.15.2973

    authors: Burgin AB Jr,Huizenga BN,Nash HA

    更新日期:1995-08-11 00:00:00

  • PaintOmics 3: a web resource for the pathway analysis and visualization of multi-omics data.

    abstract::The increasing availability of multi-omic platforms poses new challenges to data analysis. Joint visualization of multi-omics data is instrumental in better understanding interconnections across molecular layers and in fully utilizing the multi-omic resources available to make biological discoveries. We present here P...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gky466

    authors: Hernández-de-Diego R,Tarazona S,Martínez-Mira C,Balzano-Nogueira L,Furió-Tarí P,Pappas GJ Jr,Conesa A

    更新日期:2018-07-02 00:00:00

  • Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target.

    abstract::This review presents detailed information about the structure of triplet repeat RNA and addresses the simple sequence repeats of normal and expanded lengths in the context of the physiological and pathogenic roles played in human cells. First, we discuss the occurrence and frequency of various trinucleotide repeats in...

    journal_title:Nucleic acids research

    pub_type: 杂志文章,评审

    doi:10.1093/nar/gkr729

    authors: Krzyzosiak WJ,Sobczak K,Wojciechowska M,Fiszer A,Mykowska A,Kozlowski P

    更新日期:2012-01-01 00:00:00

  • Zinc ions are differentially required for the transcription of ribosomal 5S RNA and tRNA in a HeLa-cell extract.

    abstract::Chelation of divalent cations by 5 mM EDTA and subsequent removal by dialysis from a cytoplasmic HeLa cell extract leads to a complete loss of 5S rRNA transcription without affecting tRNA synthesis. Transcription complexes for 5S RNA can no longer be assembled in such a zinc-depleted extract and this ability can be fu...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/12.23.8971

    authors: Wingender E,Dilloo D,Seifart KH

    更新日期:1984-12-11 00:00:00

  • Identification of new eukaryotic tRNA genes in genomic DNA databases by a multistep weight matrix analysis of transcriptional control regions.

    abstract::A linear method for the search of eukaryotic nuclear tRNA genes in DNA databases is described. Based on a modified version of the general weight matrix procedure, our algorithm relies on the recognition of two intragenic control regions known as A and B boxes, a transcription termination signal, and on the evaluation ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/22.7.1247

    authors: Pavesi A,Conterio F,Bolchi A,Dieci G,Ottonello S

    更新日期:1994-04-11 00:00:00

  • Targeted mutagenesis of DNA with alkylating RecA assisted oligonucleotides.

    abstract::Site-specific mutation was demonstrated in a shuttle vector system using nitrogen mustard-conjugated oligodeoxyribonucleotides (ODNs). Plasmid DNA was modified in vitro by ODNs containing all four DNA bases in the presence of Escherichia coli RecA protein. Up to 50% of plasmid molecules were alkylated in the targeted ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/27.24.e38

    authors: Singer MJ,Podyminogin MA,Metcalf MA,Reed MW,Brown DA,Gamper HB,Meyer RB,Wydro RM

    更新日期:1999-12-15 00:00:00

  • Evolutionarily divergent spliceosomal snRNAs and a conserved non-coding RNA processing motif in Giardia lamblia.

    abstract::Non-coding RNAs (ncRNAs) have diverse essential biological functions in all organisms, and in eukaryotes, two such classes of ncRNAs are the small nucleolar (sno) and small nuclear (sn) RNAs. In this study, we have identified and characterized a collection of sno and snRNAs in Giardia lamblia, by exploiting our discov...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks887

    authors: Hudson AJ,Moore AN,Elniski D,Joseph J,Yee J,Russell AG

    更新日期:2012-11-01 00:00:00

  • Nanoscopic structure of DNA condensed for gene delivery.

    abstract::Scanning force microscopy was used to examine DNA condensates prepared with varying stoichiometries of lipospermine or polyethylenimine in physiological solution. For the first time, individual DNA strands were clearly visualized in incomplete condensates without drying. Using lipospermine at sub-saturating concentrat...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/25.15.3095

    authors: Dunlap DD,Maggi A,Soria MR,Monaco L

    更新日期:1997-08-01 00:00:00

  • DAXX in cancer: phenomena, processes, mechanisms and regulation.

    abstract::DAXX displays complex biological functions. Remarkably, DAXX overexpression is a common feature in diverse cancers, which correlates with tumorigenesis, disease progression and treatment resistance. Structurally, DAXX is modular with an N-terminal helical bundle, a docking site for many DAXX interactors (e.g. p53 and ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章,评审

    doi:10.1093/nar/gkz634

    authors: Mahmud I,Liao D

    更新日期:2019-09-05 00:00:00

  • Life without tRNAArg-adenosine deaminase TadA: evolutionary consequences of decoding the four CGN codons as arginine in Mycoplasmas and other Mollicutes.

    abstract::In most bacteria, two tRNAs decode the four arginine CGN codons. One tRNA harboring a wobble inosine (tRNA(Arg)ICG) reads the CGU, CGC and CGA codons, whereas a second tRNA harboring a wobble cytidine (tRNA(Arg)CCG) reads the remaining CGG codon. The reduced genomes of Mycoplasmas and other Mollicutes lack the gene en...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt356

    authors: Yokobori S,Kitamura A,Grosjean H,Bessho Y

    更新日期:2013-07-01 00:00:00

  • Efficient cDNA cloning by direct phenotypic correction of a mutant human cell line (HPRT-) using an Epstein-Barr virus-derived cDNA expression vector.

    abstract::Human cells are, in general, poor recipients of foreign DNA, which has severely hampered the cloning of genes by direct phenotypic correction of deficient human cell lines after DNA mediated gene transfer. In this communication a methodology is presented which largely circumvents this problems. The method relies on th...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/19.18.4861

    authors: Belt PB,Jongmans W,de Wit J,Hoeijmakers JH,van de Putte P,Backendorf C

    更新日期:1991-09-25 00:00:00

  • The human insulin receptor mRNA contains a functional internal ribosome entry segment.

    abstract::Regulation of mRNA translation is an important mechanism determining the level of expression of proteins in eukaryotic cells. Translation is most commonly initiated by cap-dependent scanning, but many eukaryotic mRNAs contain internal ribosome entry segments (IRESs), providing an alternative means of initiation capabl...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkp623

    authors: Spriggs KA,Cobbold LC,Ridley SH,Coldwell M,Bottley A,Bushell M,Willis AE,Siddle K

    更新日期:2009-09-01 00:00:00

  • Determinants of a transcriptionally competent environment at the GM-CSF promoter.

    abstract::Granulocyte macrophage-colony stimulating factor (GM-CSF) is produced by T cells, but not B cells, in response to immune signals. GM-CSF gene activation in response to T-cell stimulation requires remodelling of chromatin associated with the gene promoter, and these changes do not occur in B cells. While the CpG methyl...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn117

    authors: Brettingham-Moore KH,Sprod OR,Chen X,Oakford P,Shannon MF,Holloway AF

    更新日期:2008-05-01 00:00:00

  • Alternative splicing at GYNNGY 5' splice sites: more noise, less regulation.

    abstract::Numerous eukaryotic genes are alternatively spliced. Recently, deep transcriptome sequencing has skyrocketed proportion of alternatively spliced genes; over 95% human multi-exon genes are alternatively spliced. One fundamental question is: are all these alternative splicing (AS) events functional? To look into this is...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gku1253

    authors: Wang M,Zhang P,Shu Y,Yuan F,Zhang Y,Zhou Y,Jiang M,Zhu Y,Hu L,Kong X,Zhang Z

    更新日期:2014-12-16 00:00:00

  • Amino acid sequence variations in Nicotiana CRR4 orthologs determine the species-specific efficiency of RNA editing in plastids.

    abstract::In flowering plants, RNA editing is a posttranscriptional process that converts specific C to U in organelle mRNAs. Nicotiana tabacum is an allotetraploid species derived from the progenitors of Nicotiana sylvestris and Nicotiana tomentosiformis. These Nicotiana species have been used as a model for understanding the ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn629

    authors: Okuda K,Habata Y,Kobayashi Y,Shikanai T

    更新日期:2008-11-01 00:00:00

  • Flap endonuclease overexpression drives genome instability and DNA damage hypersensitivity in a PCNA-dependent manner.

    abstract::Overexpression of the flap endonuclease FEN1 has been observed in a variety of cancer types and is a marker for poor prognosis. To better understand the cellular consequences of FEN1 overexpression we utilized a model of its Saccharomyces cerevisiae homolog, RAD27. In this system, we discovered that flap endonuclease ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gky313

    authors: Becker JR,Gallo D,Leung W,Croissant T,Thu YM,Nguyen HD,Starr TK,Brown GW,Bielinsky AK

    更新日期:2018-06-20 00:00:00

  • Sequence requirement for specific interaction of an enhancer binding protein (EBP1) with DNA.

    abstract::Short DNA sequence motifs have been identified in viral and cellular enhancers which represent the binding sites for a variety of trans- acting factors. One such HeLa cell factor, EBP1, has been purified and shown to bind to sequences in the SV40 enhancer. The PRDII element in the human beta-interferon gene regulatory...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/17.2.499

    authors: Clark L,Hay RT

    更新日期:1989-01-25 00:00:00

  • Quantitation of supercoiled circular content in plasmid DNA solutions using a fluorescence-based method.

    abstract::A method for quantifying the proportion of supercoiled circular (SC) forms in DNA solutions is described. The method (SCFluo) takes advantage of the reversible denaturation property of SC forms and the high specificity of the PicoGreen fluorochrome for double-stranded (ds)DNA. Fluorescence values of forms capable of r...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/28.12.e57

    authors: Levy MS,Lotfian P,O'Kennedy R,Lo-Yim MY,Shamlou PA

    更新日期:2000-06-15 00:00:00

  • Splicing factor SF3a60 is the mammalian homologue of PRP9 of S.cerevisiae: the conserved zinc finger-like motif is functionally exchangeable in vivo.

    abstract::A cDNA encoding the 60 kDa subunit of mammalian splicing factor SF3a has been isolated. The deduced protein sequence reveals a 30% identity to the PRP9 splicing protein of the yeast S.cerevisiae. The highest homology is present in a zinc finger-like region in the C-terminal domain of both proteins. The PRP9 zinc finge...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/22.24.5223

    authors: Krämer A,Legrain P,Mulhauser F,Gröning K,Brosi R,Bilbe G

    更新日期:1994-12-11 00:00:00

  • Studies on the ability of partially iodinated 16S RNA to participate in 30S ribosome assembly.

    abstract::Deproteinated 16S RNA was iodinated at pH 5.0 in an aqueous solution containing TlCl3 plus KI for 1-5 hours at 42 degrees C. Under these conditions 33 moles of iodine are incorporated per mole of RNA. As judged by sucrose gradient sedimentation, the iodinated RNA does not exhibit any large alteration in conformation a...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/3.11.3001

    authors: Schendel PL,Craven GR

    更新日期:1976-11-01 00:00:00