{"title":"Research Progress of RNA Quadruplex.","authors":"Xiaohui Ji, Hongxia Sun, Huaxi Zhou, Junfeng Xiang, Yalin Tang, Changqi Zhao","doi":"10.1089/oli.2010.0272","DOIUrl":"10.1089/oli.2010.0272","url":null,"abstract":"<p><p>RNA/DNA sequences rich in guanine (G) can form a 4-strand structure, G-quadruplex, which has been extensively researched and observed in mammalian, fungi, and plants, with in vivo existence in eukaryotic cells. Compared with DNA quadruplex, the potential existence of RNA quadruplex appears to be generally rare; however, it is believed by some researchers to be more inevitable in vivo and speculated to play an important role where it exists. Recently, researches concerning the function of G-quadruplexes in RNAs commence, making much progress. However, there is no available review particularly focusing on RNA quadruplex till now as we know. Therefore, we decide to give a review to comprehensively summarize research progress on it. This review highlights the diverse topologies for RNA quadruplex structure and its effect factors; outlines the current knowledge of RNA quadruplex's physiological functions in biological systems, especially in gene expression; and presents the prospects of RNA quadruplex.</p>","PeriodicalId":19523,"journal":{"name":"Oligonucleotides","volume":" ","pages":"None"},"PeriodicalIF":0.0,"publicationDate":"2011-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29884511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OligonucleotidesPub Date : 2011-03-01Epub Date: 2011-03-21DOI: 10.1089/oli.2010.0271
Young Tag Ko, Ulrich Bickel, Juyang Huang
{"title":"Polyethylenimine/oligonucleotide polyplexes investigated by fluorescence resonance energy transfer and fluorescence anisotropy.","authors":"Young Tag Ko, Ulrich Bickel, Juyang Huang","doi":"10.1089/oli.2010.0271","DOIUrl":"https://doi.org/10.1089/oli.2010.0271","url":null,"abstract":"<p><p>To advance knowledge on polyplex structure and composition, fluorescence resonance energy transfer (FRET) and anisotropy measurements were applied to polyplexes of rhodamine-labeled polyethylenimine (PEI) and fluorescein-labeled double-stranded oligodeoxynucleotide (ODN). About 25 kDa PEI was compared with low-molecular-weight PEI of 2.7 kDa. FRET reached maxima at amine to phosphate (N/P) ratios of 2 and 3 for 2.7 kDa and 25 kDa PEI, respectively, with similar average distances between donor and acceptor dye molecules in polyplexes. Anisotropy measurements allowed estimating the bound fractions of PEI and ODN. At N/P = 6, all ODN was bound, but only 58% of PEI 25 kDa and 45% of PEI 2.7 kDa. In conclusion, the higher molecular weight of PEI may conformationally restrict the availability of amino groups for charge interaction with phosphate groups in ODN. Moreover, significant fractions of both types of PEI remain free in solution at N/P ratios frequently used for transfection. FRET and anisotropy measurements provide effective tools for probing polyplex compositions and designing optimized delivery systems.</p>","PeriodicalId":19523,"journal":{"name":"Oligonucleotides","volume":"21 2","pages":"109-14"},"PeriodicalIF":0.0,"publicationDate":"2011-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/oli.2010.0271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29752450","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}
{"title":"Decoy-DNA against special AT-rich sequence binding protein 1 inhibits the growth and invasive ability of human breast cancer.","authors":"Asako Yamayoshi, Mariko Yasuhara, Sanjeev Galande, Akio Kobori, Akira Murakami","doi":"10.1089/oli.2010.0277","DOIUrl":"https://doi.org/10.1089/oli.2010.0277","url":null,"abstract":"<p><p>\"Triple-negative\" (TN) breast cancers, which are characterized by estrogen receptor (-), progesterone receptor (-), and human epidermal growth factor receptor 2 (-), are typically associated with poor prognosis because of their aggressive tumor phenotypes. In recent years, the number of patients with breast cancers has remarkably increased, but there are only few available drugs for treatment of TN breast cancers. The development of novel drugs targeting TN breast cancer is urgently required. In the present study, we focused on the function of special AT-rich sequence binding protein 1 (SATB1) as a target molecule for the treatment of TN breast cancers. By recruiting chromatin remodeling enzymes and transcriptional factors, SATB1 regulates the expression of >1,000 genes related to cell growth and translocation. We synthesized a decoy DNA against SATB1, including the recognition sequence of SATB1. We examined the inhibitory effects of the decoy DNAs on cellular proliferation of a TN metastatic breast cancer cell line (MDA-MB-231). SATB1-decoy DNA inhibited the proliferation of MDA-MB-231 cells. Especially, it was significant that SATB1-decoy DNA drastically reduced the invasive and metastatic capacity of MBA-MB-231 cells. Further, in the case of MCF7 cells (SATB1-negative breast cancer cell line), SATB1-decoy DNA did not exhibit any inhibitory effect. These data suggest that SATB1-decoy DNA may be an effective candidate for use as a molecular-targeting drug for treatment of TN breast cancer.</p>","PeriodicalId":19523,"journal":{"name":"Oligonucleotides","volume":"21 2","pages":"115-21"},"PeriodicalIF":0.0,"publicationDate":"2011-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/oli.2010.0277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29823042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OligonucleotidesPub Date : 2011-03-01Epub Date: 2011-03-04DOI: 10.1089/oli.2011.0278
Jihoon Kim, Sung Wan Kim, Won Jong Kim
{"title":"PEI-g-PEG-RGD/small interference RNA polyplex-mediated silencing of vascular endothelial growth factor receptor and its potential as an anti-angiogenic tumor therapeutic strategy.","authors":"Jihoon Kim, Sung Wan Kim, Won Jong Kim","doi":"10.1089/oli.2011.0278","DOIUrl":"https://doi.org/10.1089/oli.2011.0278","url":null,"abstract":"<p><p>Tumor angiogenesis appears to be achieved by the expression of vascular endothelial growth factor (VEGF) within solid tumors that stimulate host vascular endothelial cell mitogenesis and possibly chemotaxis. VEGF's angiogenic actions are mediated through its high-affinity binding to 2 endothelium-specific receptor tyrosine kinase, Flt-1 (VEGFR1), and Flk-1/KDR (VEGFR2). RNA interference-mediated knockdown of protein expression at the messenger RNA level provides a new therapeutic strategy to overcome various diseases. To achieve high efficacy in RNA interference-mediated therapy, it is critical to develop an efficient delivering system to deliver small interference RNA (siRNA) into tissues or cells site-specifically. We previously reported an angiogenic endothelial cell-targeted polymeric gene carrier, PEI-g-PEG-RGD. This targeted carrier was developed by the conjugation of the ανβ3/ανβ5 integrin-binding RGD peptide (ACDCRGDCFC) to the cationic polymer, branched polyethylenimine, with a hydrophilic polyethylene glycol (PEG) spacer. In this study, we used PEI-g-PEG-RGD to deliver siRNA against VEGFR1 into tumor site. The physicochemical properties of PEI-g-PEG-RGD/siRNA complexes was evaluated. Further, tumor growth profile was also investigated after systemic administration of PEI-g-PEG-RGD/siRNA complexes.</p>","PeriodicalId":19523,"journal":{"name":"Oligonucleotides","volume":"21 2","pages":"101-7"},"PeriodicalIF":0.0,"publicationDate":"2011-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/oli.2011.0278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29716243","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}
OligonucleotidesPub Date : 2011-03-01Epub Date: 2011-03-21DOI: 10.1089/oli.2010.0273
R Geoffrey Sargent, Soya Kim, Dieter C Gruenert
{"title":"Oligo/polynucleotide-based gene modification: strategies and therapeutic potential.","authors":"R Geoffrey Sargent, Soya Kim, Dieter C Gruenert","doi":"10.1089/oli.2010.0273","DOIUrl":"https://doi.org/10.1089/oli.2010.0273","url":null,"abstract":"<p><p>Oligonucleotide- and polynucleotide-based gene modification strategies were developed as an alternative to transgene-based and classical gene targeting-based gene therapy approaches for treatment of genetic disorders. Unlike the transgene-based strategies, oligo/polynucleotide gene targeting approaches maintain gene integrity and the relationship between the protein coding and gene-specific regulatory sequences. Oligo/polynucleotide-based gene modification also has several advantages over classical vector-based homologous recombination approaches. These include essentially complete homology to the target sequence and the potential to rapidly engineer patient-specific oligo/polynucleotide gene modification reagents. Several oligo/polynucleotide-based approaches have been shown to successfully mediate sequence-specific modification of genomic DNA in mammalian cells. The strategies involve the use of polynucleotide small DNA fragments, triplex-forming oligonucleotides, and single-stranded oligodeoxynucleotides to mediate homologous exchange. The primary focus of this review will be on the mechanistic aspects of the small fragment homologous replacement, triplex-forming oligonucleotide-mediated, and single-stranded oligodeoxynucleotide-mediated gene modification strategies as it relates to their therapeutic potential.</p>","PeriodicalId":19523,"journal":{"name":"Oligonucleotides","volume":"21 2","pages":"55-75"},"PeriodicalIF":0.0,"publicationDate":"2011-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/oli.2010.0273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29752456","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}
OligonucleotidesPub Date : 2011-03-01Epub Date: 2011-04-05DOI: 10.1089/oli.2011.0280
Xiaoran Ding, Jing Yang, Shengqi Wang
{"title":"Antisense oligonucleotides targeting abhydrolase domain containing 2 block human hepatitis B virus propagation.","authors":"Xiaoran Ding, Jing Yang, Shengqi Wang","doi":"10.1089/oli.2011.0280","DOIUrl":"https://doi.org/10.1089/oli.2011.0280","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) infection is a major health concern worldwide and only a minority of treated patients develop a sustained protective response following a short course of therapy, and most patients require prolonged treatment to suppress viral replication. However, several recent reports showed that inhibition of certain host cell proteins prevented viral infection, specifically the human abhydrolase domain containing 2 (ABHD2) has been confirmed by our previous study to be upregulated in HepG2.2.15 cells but downregulated by lamivudine. These observations suggested that ABHD2 was important for HBV propagation and could be a target of novel anti-HBV drugs. To assess the importance of ABHD2 to the HBV infection process, antisense oligonucleotides (ASODNs) were used to downregulate ABHD2 expression in HepG2.2.15 cells. From 5 ASODNS candidates tested, AB3 significantly downregulated ABHD2 mRNA and protein expression levels. Further, AB3 significantly reduced HBV DNA, hepatitis B surface antigen, and hepatitis B \"e\" antigen protein expression levels in cell medium without affecting cell viability. These results suggest that downregulation of ABHD2 using ASODNs blocked HBV replication and expression without affecting host cell physiology. Further, data demonstrated an essential role of ABHD2 in HBV propagation, suggesting it can serve as a novel target for anti-HBV drug development.</p>","PeriodicalId":19523,"journal":{"name":"Oligonucleotides","volume":"21 2","pages":"77-84"},"PeriodicalIF":0.0,"publicationDate":"2011-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/oli.2011.0280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29792938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OligonucleotidesPub Date : 2011-03-01Epub Date: 2011-03-17DOI: 10.1089/oli.2010.0263
Ji-Young Ahn, Minjoung Jo, Pooja Dua, Dong-Ki Lee, Soyoun Kim
{"title":"A sol-gel-based microfluidics system enhances the efficiency of RNA aptamer selection.","authors":"Ji-Young Ahn, Minjoung Jo, Pooja Dua, Dong-Ki Lee, Soyoun Kim","doi":"10.1089/oli.2010.0263","DOIUrl":"https://doi.org/10.1089/oli.2010.0263","url":null,"abstract":"<p><p>RNA and DNA aptamers that bind to target molecules with high specificity and affinity have been a focus of diagnostics and therapeutic research. These aptamers are obtained by SELEX often requiring many rounds of selection and amplification. Recently, we have shown the efficient binding and elution of RNA aptamers against target proteins using a microfluidic chip that incorporates 5 sol-gel binding droplets within which specific target proteins are imbedded. Here, we demonstrate that our microfluidic chip in a SELEX experiment greatly improved selection efficiency of RNA aptamers to TATA-binding protein, reducing the number of selection cycles needed to produce high affinity aptamers by about 80%. Many aptamers were identical or homologous to those isolated previously by conventional filter-binding SELEX. The microfluidic chip SELEX is readily scalable using a sol-gel microarray-based target multiplexing. Additionally, we show that sol-gel embedded protein arrays can be used as a high-throughput assay for quantifying binding affinities of aptamers.</p>","PeriodicalId":19523,"journal":{"name":"Oligonucleotides","volume":"21 2","pages":"93-100"},"PeriodicalIF":0.0,"publicationDate":"2011-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/oli.2010.0263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29750169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OligonucleotidesPub Date : 2011-03-01Epub Date: 2011-03-17DOI: 10.1089/oli.2010.0267
Minjoung Jo, Ji-Young Ahn, Joohyung Lee, Seram Lee, Sun Woo Hong, Jae-Wook Yoo, Jeehye Kang, Pooja Dua, Dong-Ki Lee, Seunghun Hong, Soyoun Kim
{"title":"Development of single-stranded DNA aptamers for specific Bisphenol a detection.","authors":"Minjoung Jo, Ji-Young Ahn, Joohyung Lee, Seram Lee, Sun Woo Hong, Jae-Wook Yoo, Jeehye Kang, Pooja Dua, Dong-Ki Lee, Seunghun Hong, Soyoun Kim","doi":"10.1089/oli.2010.0267","DOIUrl":"https://doi.org/10.1089/oli.2010.0267","url":null,"abstract":"<p><p>The development of reagents with high affinity and specificity to small molecules is crucial for the high-throughput detection of chemical compounds, such as toxicants or pollutants. Aptamers are short and single-stranded (ss) oligonucleotides able to recognize target molecules with high affinity. Here, we report the selection of ssDNA aptamers that bind to Bisphenol A (BPA), an environmental hormone. Using SELEX process, we isolated high affinity aptamers to BPA from a 10(15) random library of 60 mer ssDNAs. The selected aptamers bound specifically to BPA, but not to structurally similar molecules, such as Bisphenol B with one methyl group difference, or 4,4'-Bisphenol with 2 methyl groups difference. Using these aptamers, we developed an aptamer-based sol-gel biochip and detected BPA dissolved in water. This novel BPA aptamer-based detection can be further applied to the universal and high-specificity detection of small molecules.</p>","PeriodicalId":19523,"journal":{"name":"Oligonucleotides","volume":"21 2","pages":"85-91"},"PeriodicalIF":0.0,"publicationDate":"2011-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/oli.2010.0267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29750173","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}
OligonucleotidesPub Date : 2011-02-01Epub Date: 2010-12-23DOI: 10.1089/oli.2010.0264
Jiehua Zhou, John J Rossi
{"title":"Cell-specific aptamer-mediated targeted drug delivery.","authors":"Jiehua Zhou, John J Rossi","doi":"10.1089/oli.2010.0264","DOIUrl":"https://doi.org/10.1089/oli.2010.0264","url":null,"abstract":"<p><p>Nucleic acid aptamers are in vitro-selected small, single-stranded DNA or RNA oligonucleotides that can specifically recognize their target on the basis of their unique 3-dimensional structures. Recent advances in the development of escort aptamers to deliver and enhance the efficacy of other therapeutic agents have drawn enthusiasm in exploiting cell-type-specific aptamers as drug delivery vehicles. This review mainly focuses on the recent developments of aptamer-mediated targeted delivery systems. We also place particular emphasis on aptamers evolved against cell membrane receptors and possibilities for translation to clinical applications.</p>","PeriodicalId":19523,"journal":{"name":"Oligonucleotides","volume":"21 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2011-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/oli.2010.0264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29555677","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}
OligonucleotidesPub Date : 2011-02-01Epub Date: 2011-01-31DOI: 10.1089/oli.2010.0259
Sibaji Sarkar, Douglas V Faller
{"title":"T-oligos inhibit growth and induce apoptosis in human ovarian cancer cells.","authors":"Sibaji Sarkar, Douglas V Faller","doi":"10.1089/oli.2010.0259","DOIUrl":"https://doi.org/10.1089/oli.2010.0259","url":null,"abstract":"<p><p>Ovarian cancer remains a leading cause of death among women worldwide, and current treatment regimens for advanced disease are inadequate. Oligonucleotides with sequence homology to telomeres (called T-oligos) have been shown to mimic DNA damage responses in cells and induce cytotoxic effects in certain tumor cell lines. We studied the effects of 2 distinct 16 mer T-oligos in 4 human ovarian epithelial carcinoma cell lines. A T-oligo with perfect homology to the telomere overhang region demonstrated some cytotoxic activity in half of the cell lines. A G-rich T-oligo derivative showed more potency and broader cytotoxic activity in these lines than the parental T-oligo. Activation of apoptotic pathways in ovarian cancer cells by exposure to the T-oligo was demonstrated by multiple independent assays. T-oligo was shown to have additive, or more than additive, activity in combination with 2 different histone deacetylase drugs currently in clinical testing. T-oligos may therefore provide a new and tumor-targeted approach to ovarian cancers.</p>","PeriodicalId":19523,"journal":{"name":"Oligonucleotides","volume":"21 1","pages":"47-53"},"PeriodicalIF":0.0,"publicationDate":"2011-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/oli.2010.0259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29638357","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}