Artificial DNA: PNA & XNA最新文献

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Adding mRNA to the list of spatially organized components in bacteria. 将mRNA添加到细菌的空间组织成分列表中。
Artificial DNA: PNA & XNA Pub Date : 2010-10-01 DOI: 10.4161/adna.1.2.14150
Thomas Bentin
{"title":"Adding mRNA to the list of spatially organized components in bacteria.","authors":"Thomas Bentin","doi":"10.4161/adna.1.2.14150","DOIUrl":"https://doi.org/10.4161/adna.1.2.14150","url":null,"abstract":"<p><p>Using LNA in situ hybridization, select mRNAs have been shown to be spatially confined to their chromosomal loci in two distantly related bacterial organisms. Translating ribosomes are diffusion limited by mRNA association.</p>","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.1.2.14150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evolution of synthetic polymers. 合成聚合物的演变。
Artificial DNA: PNA & XNA Pub Date : 2010-10-01 DOI: 10.4161/adna.1.2.13501
Alexander Roloff, Oliver Seitz
{"title":"Evolution of synthetic polymers.","authors":"Alexander Roloff,&nbsp;Oliver Seitz","doi":"10.4161/adna.1.2.13501","DOIUrl":"https://doi.org/10.4161/adna.1.2.13501","url":null,"abstract":"<p><p>A strategy for the enrichment of a DNA template that encodes a functionalized PNA oligomer is discussed. The method relies on iterated cycles of chemical translation (of the template into PNA), selection (for function), and amplification (of the survivors). Potential restrictions and future perspectives are considered.</p>","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.1.2.13501","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PNA-based microbial pathogen identification and resistance marker detection: An accurate, isothermal rapid assay based on genome-specific features. 基于pna的微生物病原体鉴定和耐药性标记检测:基于基因组特异性特征的准确等温快速检测。
Artificial DNA: PNA & XNA Pub Date : 2010-10-01 DOI: 10.4161/adna.1.2.13256
Irina Smolina, Nancy S Miller, Maxim D Frank-Kamenetskii
{"title":"PNA-based microbial pathogen identification and resistance marker detection: An accurate, isothermal rapid assay based on genome-specific features.","authors":"Irina Smolina,&nbsp;Nancy S Miller,&nbsp;Maxim D Frank-Kamenetskii","doi":"10.4161/adna.1.2.13256","DOIUrl":"https://doi.org/10.4161/adna.1.2.13256","url":null,"abstract":"<p><p>With the rapidly growing availability of the entire genome sequences of microbial pathogens, there is unmet need for increasingly sensitive systems to monitor the gene-specific markers for diagnosis of bacteremia that enables an earlier detection of causative agent and determination of drug resistance. To address these challenges, a novel FISH-type genomic sequence-based molecular technique is proposed that can identify bacteria and simultaneously detect antibiotic resistance markers for rapid and accurate testing of pathogens. The approach is based on a synergistic combination of advanced Peptide Nucleic Acid (PNA)-based technology and signal-enhancing Rolling Circle Amplification (RCA) reaction to achieve a highly specific and sensitive assay. A specific PNA-DNA construct serves as an exceedingly selective and very effective biomarker, while RCA enhances detection sensitivity and provide with a highly multiplexed assay system. Distinct-color fluorescent decorator probes are used to identify about 20-nucleotide-long signature sequences in bacterial genomic DNA and/or key genetic markers of drug resistance in order to identify and characterize various pathogens. The technique's potential and its utility for clinical diagnostics are illustrated by identification of S. aureus with simultaneous discrimination of methicillin-sensitive (MSSA) versus methicillin-resistant (MRSA) strains. Overall these promising results hint to the adoption of PNA-based rapid sensitive detection for diagnosis of other clinically relevant organisms. Thereby, new assay enables significantly earlier administration of appropriate antimicrobial therapy and may, thus have a positive impact on the outcome of the patient.</p>","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.1.2.13256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 23
Hydrogelation abilities of nucleobase-modified cytidines possessing substituted triazoles. 具有取代三唑的核碱基修饰胞苷的水凝胶化能力。
Artificial DNA: PNA & XNA Pub Date : 2010-10-01 DOI: 10.4161/adna.1.2.13975
David W Dodd, Nathan D Jones, Robert He Hudson
{"title":"Hydrogelation abilities of nucleobase-modified cytidines possessing substituted triazoles.","authors":"David W Dodd,&nbsp;Nathan D Jones,&nbsp;Robert He Hudson","doi":"10.4161/adna.1.2.13975","DOIUrl":"https://doi.org/10.4161/adna.1.2.13975","url":null,"abstract":"<p><p>Nucleoside-derived hydrogelators have been sought for their potential biomedical applications, such as are found in tissue engineering and drug delivery. By judiciously adding a degree of hydrophobicity certain analogues are able to form micelles, bi-layers and gels in water. Research in this area has yet to lay down solid ground rules for the rational design of novel nucleoside gelators making further studies necessary. The synthesis and examination of a series of aryl-substituted 5-triazolylcytidines yielded an analogue that gelates water. 5-(1-(2,2'-bithiophen-3-yl)-1H-1,2,3-triazol-4-yl)-2'-deoxycytidine was found to form gels in water down to 0.3 wt%. The ribocytidine analogue failed to form gel in aqueous solution; but was able to form a hydrogel in the presence of guanosine. Images obtained by SEM show the different architectures of the gel; varying from cribriform to fibrous to lamellar. The present gelating compound studied may have potential as a component of a controlled-release drug delivery system.</p>","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.1.2.13975","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Improving gene silencing of siRNAs via tricyclo-DNA modification. 通过三环dna修饰改善sirna的基因沉默。
Artificial DNA: PNA & XNA Pub Date : 2010-07-01 DOI: 10.4161/adna.1.1.11385
Damian Ittig, Samuel Luisier, Jan Weiler, Daniel Schümperli, Christian J Leumann
{"title":"Improving gene silencing of siRNAs via tricyclo-DNA modification.","authors":"Damian Ittig,&nbsp;Samuel Luisier,&nbsp;Jan Weiler,&nbsp;Daniel Schümperli,&nbsp;Christian J Leumann","doi":"10.4161/adna.1.1.11385","DOIUrl":"https://doi.org/10.4161/adna.1.1.11385","url":null,"abstract":"<p><p>Small interfering RNAs (siRNAs) can be exploited for the selective silencing of disease-related genes via the RNA interference (RNAi) machinery and therefore raise hope for future therapeutic applications. Especially chemically modified siRNAs are of interest as they are expected to convert lead siRNA sequences into effective drugs. To study the potential of tricyclo-DNA (tc-DNA) in this context we systematically incorporated tc-DNA units at various positions in a siRNA duplex targeted to the EGFP gene that was expressed in HeLa cells. Silencing activity was measured by FACS, mRNA levels were determined by RT-PCR and the biostability of the modifed siRNAs was determined in human serum. We found that modifications in the 3'-overhangs in both the sense and antisense strands were compatible with the RNAi machinery leading to similar activities compared to wild-type (wt) siRNA. Additional modifications at the 3'-end, the 5'-end and in the center of the sense (passenger) strand were also well tolerated and did not compromise activity. Extensive modifications of the 3'- and the 5'-end in the antisense (guide) strand, however, abolished RNAi activity. Interestingly, modifications in the center of the duplex on both strands, corresponding to the position of the cleavage site by AGO2, increased efficacy relative to wt by a factor of 4 at the lowest concentrations (2 nM) investigated. In all cases, reduction of EGFP fluorescence was accompanied with a reduction of the EGFP mRNA level. Serum stability analysis further showed that 3'-overhang modifications only moderately increased stability while more extensive substitution by tc-DNA residues significantly enhanced biostability.</p>","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.1.1.11385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Introducing Artificial DNA: PNA & XNA. 介绍人工DNA: PNA和XNA。
Artificial DNA: PNA & XNA Pub Date : 2010-07-01 DOI: 10.4161/adna.1.1.12932
Peter E Nielsen
{"title":"Introducing Artificial DNA: PNA & XNA.","authors":"Peter E Nielsen","doi":"10.4161/adna.1.1.12932","DOIUrl":"https://doi.org/10.4161/adna.1.1.12932","url":null,"abstract":"","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.1.1.12932","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Inhibition of hepatitis B virus replication in vivo using lipoplexes containing altritol-modified antiviral siRNAs. 含altritol修饰的抗病毒sirna的脂质体在体内抑制乙型肝炎病毒复制
Artificial DNA: PNA & XNA Pub Date : 2010-07-01 DOI: 10.4161/adna.1.1.11981
Justin Hean, Carol Crowther, Abdullah Ely, Rafique Ul Islam, Samantha Barichievy, Kristie Bloom, Marc S Weinberg, Willem Al van Otterlo, Charles B de Koning, Felix Salazar, Patricia Marion, Eric B Roesch, Marc Lemaitre, Piet Herdewijn, Patrick Arbuthnot
{"title":"Inhibition of hepatitis B virus replication in vivo using lipoplexes containing altritol-modified antiviral siRNAs.","authors":"Justin Hean,&nbsp;Carol Crowther,&nbsp;Abdullah Ely,&nbsp;Rafique Ul Islam,&nbsp;Samantha Barichievy,&nbsp;Kristie Bloom,&nbsp;Marc S Weinberg,&nbsp;Willem Al van Otterlo,&nbsp;Charles B de Koning,&nbsp;Felix Salazar,&nbsp;Patricia Marion,&nbsp;Eric B Roesch,&nbsp;Marc Lemaitre,&nbsp;Piet Herdewijn,&nbsp;Patrick Arbuthnot","doi":"10.4161/adna.1.1.11981","DOIUrl":"https://doi.org/10.4161/adna.1.1.11981","url":null,"abstract":"<p><p>Chronic infection with the hepatitis B virus (HBV) occurs in approximately 6% of the world's population and carriers of the virus are at risk for complicating hepatocellular carcinoma. Current treatment options have limited efficacy and chronic HBV infection is likely to remain a significant global medical problem for many years to come. Silencing HBV gene expression by harnessing RNA interference (RNAi) presents an attractive option for development of novel and effective anti HBV agents. However, despite significant and rapid progress, further refinement of existing technologies is necessary before clinical application of RNAi-based HBV therapies is realized. Limiting off target effects, improvement of delivery efficiency, dose regulation and preventing reactivation of viral replication are some of the hurdles that need to be overcome. To address this, we assessed the usefulness of the recently described class of altritol-containing synthetic siRNAs (ANA siRNAs), which were administered as lipoplexes and tested in vivo in a stringent HBV transgenic mouse model. Our observations show that ANA siRNAs are capable of silencing of HBV replication in vivo. Importantly, non specific immunostimulation was observed with unmodified siRNAs and this undesirable effect was significantly attenuated by ANA modification. Inhibition of HBV replication of approximately 50% was achieved without evidence for induction of toxicity. These results augur well for future application of ANA siRNA therapeutic lipoplexes.</p>","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.1.1.11981","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 37
Mega-cloning and the advent of synthetic genomes. 大规模克隆和合成基因组的出现。
Artificial DNA: PNA & XNA Pub Date : 2010-07-01 DOI: 10.4161/adna.1.1.12935
Lise Goltermann, Thomas Bentin
{"title":"Mega-cloning and the advent of synthetic genomes.","authors":"Lise Goltermann,&nbsp;Thomas Bentin","doi":"10.4161/adna.1.1.12935","DOIUrl":"https://doi.org/10.4161/adna.1.1.12935","url":null,"abstract":"<p><p>Molecular biology owes its prominent role in the biological sciences to the tools of recombinant DNA. While the foundations of recombinant DNA were laid in the 1970s with the discovery of type II restriction endonucleases,1,2 development of robust sequencing technology3 and pioneering work on gene synthesis,4,5 it was not until the turn of the new millennium before the first complete synthetic viral genomes saw the light of day including that of hepatitis C,6 poliovirus,7 and bacteriophage PhiX174.8 Recombinant DNA has come of age as entire cellular genomes are sequenced and stored as digitized information. So what's next? One novel branch of recombinant DNA, referred to as synthetic genomics,9 is occupied with (re)construction of entire cellular genomes from virtual sequence information and using chemical components. Here we look at the most recent developments in such de novo construction. For a broader and more extensive review on genome engineering, the reader is referred to the excellent paper by Carr and Church.10.</p>","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.1.1.12935","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Peptide nucleic acid probes with charged photocleavable mass markers: Towards PNA-based MALDI-TOF MS genetic analysis. 带电荷光可切割质量标记的肽核酸探针:基于pna的MALDI-TOF质谱遗传分析。
Artificial DNA: PNA & XNA Pub Date : 2010-07-01 DOI: 10.4161/adna.1.1.12199
Rachel J Ball, Philip S Green, Nittaya Gale, G John Langley, Tom Brown
{"title":"Peptide nucleic acid probes with charged photocleavable mass markers: Towards PNA-based MALDI-TOF MS genetic analysis.","authors":"Rachel J Ball,&nbsp;Philip S Green,&nbsp;Nittaya Gale,&nbsp;G John Langley,&nbsp;Tom Brown","doi":"10.4161/adna.1.1.12199","DOIUrl":"https://doi.org/10.4161/adna.1.1.12199","url":null,"abstract":"<p><p>Halogen-labelled peptide organic acid (HPOA) monomers have been synthesised and incorporated into sequence-specific peptide nucleic acid (PNA) probes. Three different types of probe have been prepared; the unmodified PNA probe, the PNA probe with a mass marker, and the PNA probe with photocleavable mass marker. All three types of probe have been used in model studies to develop a mass spectrometry-based hybridisation assay for detection of point mutations in DNA.</p>","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.1.1.12199","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
In vivo efficacy and off-target effects of locked nucleic acid (LNA) and unlocked nucleic acid (UNA) modified siRNA and small internally segmented interfering RNA (sisiRNA) in mice bearing human tumor xenografts. 经锁定核酸(LNA)和解锁核酸(UNA)修饰的 siRNA 和小型内部分段干扰 RNA(sisiRNA)在携带人类肿瘤异种移植物的小鼠中的体内疗效和脱靶效应。
Artificial DNA: PNA & XNA Pub Date : 2010-07-01 DOI: 10.4161/adna.1.1.12204
Orf Mook, Jeroen Vreijling, Suzy L Wengel, Jesper Wengel, Chuanzheng Zhou, Jyoti Chattopadhyaya, Frank Baas, Kees Fluiter
{"title":"In vivo efficacy and off-target effects of locked nucleic acid (LNA) and unlocked nucleic acid (UNA) modified siRNA and small internally segmented interfering RNA (sisiRNA) in mice bearing human tumor xenografts.","authors":"Orf Mook, Jeroen Vreijling, Suzy L Wengel, Jesper Wengel, Chuanzheng Zhou, Jyoti Chattopadhyaya, Frank Baas, Kees Fluiter","doi":"10.4161/adna.1.1.12204","DOIUrl":"10.4161/adna.1.1.12204","url":null,"abstract":"<p><p>The clinical use of small interfering RNA (siRNA) is hampered by poor uptake by tissues and instability in circulation. In addition, off-target effects pose a significant additional problem for therapeutic use of siRNA. Chemical modifications of siRNA have been reported to increase stability and reduce off-target effects enabling possible therapeutic use of siRNA. Recently a large scale direct comparison of the impact of 21 different types of novel chemical modifications on siRNA efficiency and cell viability was published.1 It was found that several types of chemical modifications could enhance siRNA activity beyond that of an unmodified siRNA in vitro. In addition, a novel siRNA design, termed small internally segmented interfering RNA (sisiRNA), composed of an intact antisense strand and segmented guide strand stabilized using LNA was shown to be effective in cell based assays. In the present study we examined the in vivo efficacy of the LNA and UNA modified siRNA and sisiRNA in a mouse model bearing human tumor xenografts. We studied the biodistribution and efficacy of target knockdown in the mouse model. In addition we used whole genome profiling to assess the off-target effects in the liver of the mouse and the tumor xenografts. We report that LNA and UNA modified siRNA and sisiRNA improve the efficacy in target knockdown as compared with unmodified siRNA in the tumor xenografts without formulation. However, the level of off-target gene regulation in both the tumor and the liver correlated with the increase in efficacy in target knockdown, unless the seed region of the siRNA was modified.</p>","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109444/pdf/adna0101_0036.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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