Abstract：
:The available reagents for the attachment of functional moieties to plasmid DNA are limiting. Most reagents bind plasmid DNA in a non-sequence- specific manner, with undefined stoichiometry, and affect DNA charge and delivery properties or involve chemical modifications that abolish gene expression. The design and ability of oligonucleotides (ODNs) containing locked nucleic acids (LNAs) to bind supercoiled, double-stranded plasmid DNA in a sequence-specific manner are described for the first time. The main mechanism for LNA ODNs binding plasmid DNA is demonstrated to be by strand displacement. LNA ODNs are more stably bound to plasmid DNA than similar peptide nucleic acid (PNA) 'clamps' for procedures such as particle-mediated DNA delivery (gene gun). It is shown that LNA ODNs remain associated with plasmid DNA after cationic lipid-mediated transfection into mammalian cells. LNA ODNs can bind to DNA in a sequence-specific manner so that binding does not interfere with plasmid conformation or gene expression. Attachment of CpG-based immune adjuvants to plasmid by 'hybrid' phosphorothioate-LNA ODNs induces tumour necrosis factor-alpha production in the macrophage cell line RAW264.7. This observation exemplifies an important new, controllable methodology for adding functionality to plasmids for gene delivery and DNA vaccination.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Hertoghs KM,Ellis JH,Catchpole IRdoi
10.1093/nar/gkg801keywords:
subject
Has Abstractpub_date
2003-10-15 00:00:00pages
5817-30issue
20eissn
0305-1048issn
1362-4962journal_volume
31pub_type
杂志文章abstract：:The cloned 18 S ribosomal RNA gene from Saccharomyces cerevisiae have been sequenced, using the Maxam-Gilbert procedure. From this data the complete sequence of 1789 nucleotides of the 18 S RNA was deduced. Extensive homology with many eucaryotic as well as E. coli ribosomal small subunit rRNA (S-rRNA) has been observ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/8.23.5779
更新日期：1980-12-11 00:00:00
abstract：:Transcription initiation complexes formed by bacterial RNA polymerases (RNAPs) exhibit dramatic species-specific differences in stability, leading to different strategies of transcription regulation. The molecular basis for this diversity is unclear. Promoter complexes formed by RNAP from Thermus aquaticus (Taq) are c...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gks973
更新日期：2012-12-01 00:00:00
abstract：:A-tracts are functionally important DNA sequences which induce helix bending and have peculiar structural properties. While A-tract structure has been qualitatively well characterized, their mechanical properties remain controversial. A-tracts appear structurally rigid and resist nucleosome formation, but seem flexibl...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gku338
更新日期：2014-06-01 00:00:00
abstract：:We report a crystal structure that shows an antibiotic that extracts a nucleobase from a DNA molecule 'caught in the act' after forming a covalent bond but before departing with the base. The structure of trioxacarcin A covalently bound to double-stranded d(AACCGGTT) was determined to 1.78 A resolution by MAD phasing ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkn245
更新日期：2008-06-01 00:00:00
abstract：:The modulation of GLI2, an oncogenic transcription factor commonly upregulated in cancer, is in many cases not due to genetic defects, suggesting dysregulation through alternative mechanisms. The identity of these molecular events remains for the most part unknown. Here, we identified TFII-I as a novel repressor of GL...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkaa476
更新日期：2020-07-27 00:00:00
abstract：:We have isolated the mouse MyoD1 gene flanked by its promoter region by screening a genomic library with synthetic oligonucleotides. The structural gene is interrupted by two G + C rich introns. Transfection of the cloned gene inserted into an expression vector converts fibroblasts to myoblasts. Sequence analysis of a...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/19.23.6433
更新日期：1991-12-11 00:00:00
abstract：:Xenbase (www.xenbase.org), the model organism database for Xenopus laevis and X. (Silurana) tropicalis, is the principal centralized resource of genomic, development data and community information for Xenopus research. Recent improvements include the addition of the literature and interaction tabs to gene catalog page...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkp953
更新日期：2010-01-01 00:00:00
abstract：:MicroRNAs are small (approximately 22 nt) RNAs that regulate gene expression and play important roles in both normal and disease physiology. The use of microarrays for global characterization of microRNA expression is becoming increasingly popular and has the potential to be a widely used and valuable research tool. H...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkn932
更新日期：2009-02-01 00:00:00
abstract：:The allele frequency net database (http://www.allelefrequencies.net) is an online repository that contains information on the frequencies of immune genes and their corresponding alleles in different populations. The extensive variability observed in genes and alleles related to the immune system response and its signi...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkq1128
更新日期：2011-01-01 00:00:00
abstract：:The SPARC gene 5'flanking sequence has been shown to contain enhancer elements, but also negative control elements immediately upstream of the enhancer elements. Although these 5'enhancer elements are active in F9 and PYS-2 cells, their activities are nullified by the 5'repressor activity. In the present study we have...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/25.15.3169
更新日期：1997-08-01 00:00:00
abstract：:Genotoxic stress induces alternative splicing of the oncogene MDM2 generating MDM2-ALT1, an isoform attributed with tumorigenic properties. However, the mechanisms underlying this event remain unclear. Here we explore MDM2 splicing regulation by utilizing a novel minigene that mimics endogenous MDM2 splicing in respon...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv223
更新日期：2015-04-30 00:00:00
abstract：:The Genomes Online Database (GOLD) (https://gold.jgi.doe.gov) is a manually curated data management system that catalogs sequencing projects with associated metadata from around the world. In the current version of GOLD (v.6), all projects are organized based on a four level classification system in the form of a Stud...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkw992
更新日期：2017-01-04 00:00:00
abstract：:In 2.5 x 10(-4)M EDTA buffer, the derivative melting curve of calf thymus DNA shows a major band at 47 degrees with a shoulder at about 54 degrees . The fraction of melting area of this shoulder is about 13%. For reconstituted polylysine-calf thymus DNA complexes, in addition to the melting of free DNA regions at abou...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/1.2.257
更新日期：1974-02-01 00:00:00
abstract：:Insertion of the insertion sequence Is2(I) directly before the galE gene of the galactose operon results in a Gal minus phenotype (1, 2). The Gal-constitutive allele galc200 (and its deletion derivative galc200 delta 31) arise from such a Gal minus mutant by the insertion of LS2(II) DNA within the LS2(I) sequence (3)....
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/10.16.5015
更新日期：1982-08-25 00:00:00
abstract：:CDK12 (cyclin-dependent kinase 12) is a regulatory kinase with evolutionarily conserved roles in modulating transcription elongation. Recent tumor genome studies of breast and ovarian cancers highlighted recurrent CDK12 mutations, which have been shown to disrupt DNA repair in cell-based assays. In breast cancers, CDK...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkx187
更新日期：2017-06-20 00:00:00
abstract：:Splicing is a biological phenomenon that removes the non-coding sequence from the transcripts to produce a mature transcript suitable for translation. To study this phenomenon, information on the intron-exon arrangement of a gene is essential, usually obtained by aligning mRNA/EST sequences to their cognate genomic se...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkg561
更新日期：2003-07-01 00:00:00
abstract：:Antimicrobial peptides (AMPs) are gaining importance as anti-infective agents. Here we describe the updated Collection of Antimicrobial Peptide (CAMP) database, available online at http://www.camp.bicnirrh.res.in/. The 3D structures of peptides are known to influence antimicrobial activity. Although there exists datab...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt1157
更新日期：2014-01-01 00:00:00
abstract：:Members of several classes of proto-oncogenes replicate during the first third of S-phase in two human (K562 erythroleukemia and HeLa), one Chinese hamster (CHO) and eight mouse cell lines. These cell lines exhibit a variety of specialized functions characteristic of pre-B and B cells, T cells and erythroid cells. The...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/15.1.87
更新日期：1987-01-12 00:00:00
abstract：:Rotaviruses are a major cause of acute, often fatal, gastroenteritis in infants and young children world-wide. Virions contain an 11 segment double-stranded RNA genome. Little is known about the cis-acting sequences and structural elements of the viral RNAs. Using a database of 1621 full-length sequences of mammalian ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkq663
更新日期：2010-11-01 00:00:00
abstract：:Gene set enrichment testing can enhance the biological interpretation of ChIP-seq data. Here, we develop a method, ChIP-Enrich, for this analysis which empirically adjusts for gene locus length (the length of the gene body and its surrounding non-coding sequence). Adjustment for gene locus length is necessary because ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gku463
更新日期：2014-07-01 00:00:00
abstract：:African trypanosomes are extracellular protozoan parasites that are transmitted from one mammalian host to the next by tsetse flies. Bloodstream forms express variant surface glycoprotein (VSG); the tsetse fly (procyclic) forms express instead the procyclic acidic repetitive protein (PARP). PARP mRNA is abundant in pr...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/24.7.1202
更新日期：1996-04-01 00:00:00
abstract：:Human thymine-DNA glycosylase (TDG) is well known to excise thymine and uracil from G.T and G.U mismatches, respectively, and was therefore proposed to play a central role in the cellular defense against genetic mutation through spontaneous deamination of 5-methylcytosine and cytosine. In this study, we characterized ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkg344
更新日期：2003-05-01 00:00:00
abstract：:We investigate the role of water molecules in 89 protein-RNA complexes taken from the Protein Data Bank. Those with tRNA and single-stranded RNA are less hydrated than with duplex or ribosomal proteins. Protein-RNA interfaces are hydrated less than protein-DNA interfaces, but more than protein-protein interfaces. Majo...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gku679
更新日期：2014-09-01 00:00:00
abstract：:We describe an algorithm for gene identification in DNA sequences derived from shotgun sequencing of microbial communities. Accurate ab initio gene prediction in a short nucleotide sequence of anonymous origin is hampered by uncertainty in model parameters. While several machine learning approaches could be proposed t...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkq275
更新日期：2010-07-01 00:00:00
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
更新日期：2014-12-16 00:00:00
abstract：:The chromatin structure of yeast ribosomal DNA was analyzed in vivo by crosslinking intact cells with psoralen. We found that in exponentially growing cultures the regions coding for the 35S rRNA precursor fall into two distinct classes. One class was highly accessible to psoralen and associated with nascent RNAs, cha...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/21.10.2331
更新日期：1993-05-25 00:00:00
abstract：:The accumulation of somatic mitochondrial DNA (mtDNA) mutations contributes to the pathogenesis of human disease. Currently, mitochondrial mutations are largely considered results of inaccurate processing of its heavily damaged genome. However, mainly from a lack of methods to monitor mtDNA mutations with sufficient s...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkw716
更新日期：2016-10-14 00:00:00
abstract：:The Zebrafish Information Network (ZFIN) (https://zfin.org/) is the database for the model organism, zebrafish (Danio rerio). ZFIN expertly curates, organizes, and provides a wide array of zebrafish genetic and genomic data, including genes, alleles, transgenic lines, gene expression, gene function, mutant phenotypes,...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkaa1010
更新日期：2021-01-08 00:00:00
abstract：:A cDNA library was constructed from the mRNA of the ZR-75 oestrogen responsive human breast cancer cell line and screened for oestrogen regulated mRNA sequences. Of the recombinants isolated, 30 contained cDNA that corresponded to a single mRNA species of 2.1 kb that was induced between 10 and 15 fold by oestradiol tr...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/15.9.3773
更新日期：1987-05-11 00:00:00
abstract：:Human single-strand (ss) DNA binding proteins 1 (hSSB1) has been shown to participate in DNA damage response and maintenance of genome stability by regulating the initiation of ATM-dependent signaling. ATM phosphorylates hSSB1 and prevents hSSB1 from ubiquitin-proteasome-mediated degradation. However, the E3 ligase th...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gku876
更新日期：2014-10-01 00:00:00
