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Antisense oligonucleotide

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https://www.readbyqxmd.com/read/28106744/oligonucleotide-therapy-for-obstructive-and-restrictive-respiratory-diseases
#1
REVIEW
Wupeng Liao, Jinrui Dong, Hong Yong Peh, Lay Hong Tan, Kah Suan Lim, Li Li, Wai-Shiu Fred Wong
Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28080251/tetrahedral-dna-nanoparticle-vector-for-intracellular-delivery-of-targeted-peptide-nucleic-acid-antisense-agents-to-restore-antibiotic-sensitivity-in-cefotaxime-resistant-escherichia-coli
#2
John Benedict Readman, George Dickson, Nick G Coldham
The bacterial cell wall presents a barrier to the uptake of unmodified synthetic antisense oligonucleotides, such as peptide nucleic acids, and so is one of the greatest obstacles to the development of their use as therapeutic anti-bacterial agents. Cell-penetrating peptides have been covalently attached to antisense agents, to facilitate penetration of the bacterial cell wall and deliver their cargo into the cytoplasm. Although they are an effective vector for antisense oligonucleotides, they are not specific for bacterial cells and can exhibit growth inhibitory properties at higher doses...
January 12, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28080221/molecular-mechanisms-of-antisense-oligonucleotides
#3
Stanley T Crooke
In 1987, when I became interested in the notion of antisense technology, I returned to my roots in RNA biochemistry and began work to understand how oligonucleotides behave in biological systems. Since 1989, my research has focused primarily on this topic, although I have been involved in most areas of research in antisense technology. I believe that the art of excellent science is to frame large important questions that are perhaps not immediately answerable with existing knowledge and methods, and then conceive a long-term (multiyear) research strategy that begins by answering the most pressing answerable questions on the path to the long-term goals...
January 12, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28078998/lipoprotein-a-management-pharmacological-and-apheretic-treatment
#4
Ruth Hanssen, Ioanna Gouni-Berthold
Lipoprotein (a) [Lp(a)] is an low-density lipoprotein (LDL)-like particle with an additional apolipoprotein, apolipoprotein (a), [apo(a)] attached to apolipoprotein B. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) is causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). The risk association between Lp(a) concentrations and CVD is still controversial but seems to be continuous and without an obvious threshold Lp(a) level. Circulating concentrations of Lp(a) are genetically determined; desirable levels are amplt; 50 mg/dl...
12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28064104/dermal-transdermal-delivery-of-small-interfering-rna-and-antisense-oligonucleotides-advances-and-hurdles
#5
REVIEW
Kevin Ita
A diverse array of nucleic acids has been studied by several researchers for the management of several diseases. Among these compounds, small interfering RNA and antisense oligonucleotides have attracted considerable attention. Antisense oligonucleotides are synthetic single stranded strings of nucleic acids that bind to RNA and thereby alter or reduce expression of the target RNA while siRNAs, on the other hand, are double-stranded RNA molecules which can hybridize with a specific mRNA sequence and block the translation of numerous genes...
January 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28054653/the-long-non-coding-rna-neat1-is-responsive-to-neuronal-activity-and-is-associated-with-hyperexcitability-states
#6
Guy Barry, James A Briggs, Do Won Hwang, Sam P Nayler, Patrick R J Fortuna, Nicky Jonkhout, Fabien Dachet, Jesper L V Maag, Pieter Mestdagh, Erin M Singh, Lotta Avesson, Dominik C Kaczorowski, Ezgi Ozturk, Nigel C Jones, Irina Vetter, Luis Arriola-Martinez, Jianfei Hu, Gloria R Franco, Victoria M Warn, Andrew Gong, Marcel E Dinger, Frank Rigo, Leonard Lipovich, Margaret J Morris, Terence J O'Brien, Dong Soo Lee, Jeffrey A Loeb, Seth Blackshaw, John S Mattick, Ernst J Wolvetang
Despite their abundance, the molecular functions of long non-coding RNAs in mammalian nervous systems remain poorly understood. Here we show that the long non-coding RNA, NEAT1, directly modulates neuronal excitability and is associated with pathological seizure states. Specifically, NEAT1 is dynamically regulated by neuronal activity in vitro and in vivo, binds epilepsy-associated potassium channel-interacting proteins including KCNAB2 and KCNIP1, and induces a neuronal hyper-potentiation phenotype in iPSC-derived human cortical neurons following antisense oligonucleotide knockdown...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28053087/targeting-traf3ip2-by-genetic-and-interventional-approaches-inhibits-ischemia-reperfusion-induced-myocardial-injury-and-adverse-remodeling
#7
John M Erikson, Anthony J Valente, Srinivas Mummidi, Hemanthkumar Kandikattu, Vincent G DeMarco, Shawn B Bender, William P Fay, Ulrich Siebenlist, Bysani Chandrasekar
Re-establishing blood supply is the primary goal for reducing myocardial injury in subjects with ischemic heart disease. Paradoxically, reperfusion results in oxidative stress and a marked inflammatory response in the heart. TRAF3IP2 (TRAF3 Interacting Protein 2; previously known as CIKS or Act1) is an oxidative stress-responsive cytoplasmic adapter molecule that is an upstream regulator of both IκB kinase (IKK) and c-Jun N-terminal kinase (JNK), and an important mediator of autoimmune and inflammatory responses...
January 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28053071/mouse-models-for-drug-discovery-can-new-tools-and-technology-improve-translational-power
#8
Aamir Zuberi, Cathleen Lutz
The use of mouse models in biomedical research and preclinical drug evaluation is on the rise. The advent of new molecular genome-altering technologies such as CRISPR/Cas9 allows for genetic mutations to be introduced into the germ line of a mouse faster and less expensively than previous methods. In addition, the rapid progress in the development and use of somatic transgenesis using viral vectors, as well as manipulations of gene expression with siRNAs and antisense oligonucleotides, allow for even greater exploration into genomics and systems biology...
December 2016: ILAR Journal
https://www.readbyqxmd.com/read/28051352/antisense-oligonucleotides-targeting-raf-1-block-japanese-encephalitis-virus-in-vitro-and-in-vivo
#9
Li Zhang, Qingjun Li, Xiaoran Ding, Bo Zhang, Qiling Zhang, Xinyan Qu, Yujia Huo, Jing Yang, Shengqi Wang
Japanese encephalitis virus (JEV) infections represent a major health concern in Southeast Asia since no effective treatments are available. Recently, several reports have demonstrated that inhibition of certain host cell proteins prevents viral infection. Raf-1 kinase is a central component of many signaling pathways involved in normal cell growth and oncogenic transformation, and Ras/Raf/ERK signaling activation has been observed during viral infections (including JEV infection). In this study, Raf-1 was confirmed to be upregulated by JEV infection, which suggested that Raf-1 might be important for JEV infection and might be a target for novel anti-JEV drugs...
January 4, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28045030/small-rna-zippers-lock-mirna-molecules-and-block-mirna-function-in-mammalian-cells
#10
Lingyu Meng, Cuicui Liu, Jinhui Lü, Qian Zhao, Shengqiong Deng, Guangxue Wang, Jing Qiao, Chuyi Zhang, Lixiao Zhen, Ying Lu, Wenshu Li, Yuzhen Zhang, Richard G Pestell, Huiming Fan, Yi-Han Chen, Zhongmin Liu, Zuoren Yu
MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed 'small RNA zipper'. It is designed to connect miRNA molecules end to end, forming a DNA-RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30-50 nM small RNA zippers...
January 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28042781/mir-21-an-oncogenic-target-mirna-for-cancer-therapy-molecular-mechanisms-and-recent-advancements-in-chemo-and-radio-resistance
#11
Sanaz Javanmardi, Mahmoud Reza Aghamaali, Samira Sadat Abolmaali, Samaneh Mohammadi, Ali Mohammad Tamaddon
In the past decade, miRNAs have been extensively attracted the scientist's attentions as tumor suppressors or oncogenes that have been implicated in tumor progression, metastasis and intrinsic resistance to various cancer therapies. microRNA-21 (miR-21) demonstrates a potential oncogenic function and target tumor inhibitor proteins in almost all types of cancer. miR-21 overexpression has been studied in terms of cell proliferation, migration, invasion, metastasis, and apoptosis regulation.Inhibition of miRNA expression using antisense technology by various nanovectors of different sizes, shapes and compositions has been evolved progressively to overcome the barriers confronted by miRNA delivery...
January 1, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28036257/epigenetic-therapy-in-urologic-cancers-an-update-on-clinical-trials
#12
REVIEW
Inês Faleiro, Ricardo Leão, Alexandra Binnie, Ramon Andrade de Mello, Ana-Teresa Maia, Pedro Castelo-Branco
Epigenetic dysregulation is one of many factors that contribute to cancer development and progression. Numerous epigenetic alterations have been identified in urologic cancers including histone modifications, DNA methylation changes, and microRNA expression. Since these changes are reversible, efforts are being made to develop epigenetic drugs that restore the normal epigenetic patterns of cells, and many clinical trials are already underway to test their clinical potential. In this review we analyze multiple clinical trials (n=51) that test the efficacy of these drugs in patients with urologic cancers...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28026123/liposomal-spherical-nucleic-acids-for-regulating-long-noncoding-rnas-in-the-nucleus
#13
Anthony J Sprangers, Liangliang Hao, Resham J Banga, Chad A Mirkin
Emerging evidence indicates that long noncoding RNAs (lncRNAs) are actively involved in a number of developmental and tumorigenic processes. Here, the authors describe the first successful use of spherical nucleic acids as an effective nanoparticle platform for regulating lncRNAs in cells; specifically, for the targeted knockdown of the nuclear-retained metastasis associated lung adenocarcinoma transcript 1 (Malat1), a key oncogenic lncRNA involved in metastasis of several cancers. Utilizing the liposomal spherical nucleic acid (LSNA) constructs, the authors first explored the delivery of antisense oligonucleotides to the nucleus...
December 27, 2016: Small
https://www.readbyqxmd.com/read/28018102/apolipoprotein-b100-is-required-for-hepatitis-c-infectivity-and-mipomersen-inhibits-hepatitis-c
#14
Esperance A K Schaefer, James Meixiong, Christina Mark, Amy Deik, Daniel L Motola, Dahlene Fusco, Andrew Yang, Cynthia Brisac, Shadi Salloum, Wenyu Lin, Clary B Clish, Lee F Peng, Raymond T Chung
AIM: To characterize the role of apolipoprotein B100 (apoB100) in hepatitis C viral (HCV) infection. METHODS: In this study, we utilize a gene editing tool, transcription activator-like effector nucleases (TALENs), to generate human hepatoma cells with a stable genetic deletion of APOB to assess of apoB in HCV. Using infectious cell culture-competent HCV, viral pseudoparticles, replicon models, and lipidomic analysis we determined the contribution of apoB to each step of the viral lifecycle...
December 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28017471/the-antisense-transcript-smn-as1-regulates-smn-expression-and-is-a-novel-therapeutic-target-for-spinal-muscular-atrophy
#15
Constantin d'Ydewalle, Daniel M Ramos, Noah J Pyles, Shi-Yan Ng, Mariusz Gorz, Celeste M Pilato, Karen Ling, Lingling Kong, Amanda J Ward, Lee L Rubin, Frank Rigo, C Frank Bennett, Charlotte J Sumner
The neuromuscular disorder spinal muscular atrophy (SMA), the most common inherited killer of infants, is caused by insufficient expression of survival motor neuron (SMN) protein. SMA therapeutics development efforts have focused on identifying strategies to increase SMN expression. We identified a long non-coding RNA (lncRNA) that arises from the antisense strand of SMN, SMN-AS1, which is enriched in neurons and transcriptionally represses SMN expression by recruiting the epigenetic Polycomb repressive complex-2...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28007899/use-of-antisense-oligonucleotides-to-correct-the-splicing-error-in-iscu-myopathy-patient-cell-lines
#16
Gregory P Holmes-Hampton, Daniel R Crooks, Ronald G Haller, Shuling Guo, Susan M Freier, Brett P Monia, Tracey A Rouault
ISCU myopathy is an inherited disease that primarily affects individuals of northern Swedish descent who share a single point mutation in the fourth intron of the ISCU gene. The current study shows correction of specific phenotypes associated with disease following treatment with an antisense oligonucleotide (ASO) targeted to the site of the mutation. We have shown that ASO treatment diminished aberrant splicing and increased ISCU protein levels in both patient fibroblasts and patient myotubes in a concentration dependent fashion...
October 7, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28007532/role-of-g-protein-coupled-estrogen-receptor-gper-gpr30-in-maintenance-of-meiotic-arrest-in-fish-oocytes
#17
REVIEW
Peter Thomas
An essential role for GPER (formerly known as GPR30) in regulating mammalian reproduction has not been identified to date, although it has shown to be involved in the regulation a broad range of other estrogen-dependent functions. In contrast, an important reproductive role for GPER in the maintenance of oocyte meiotic arrest has been identified in teleost fishes, which is briefly reviewed here. Recent studies have clearly shown that ovarian follicle production of estradiol-17β (E2) maintains meiotic arrest in several teleost species through activation of GPER coupled to a stimulatory G protein (Gs) on oocyte plasma membranes resulting in stimulation of cAMP production and maintenance of elevated cAMP levels...
December 19, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28005462/recognition-of-c9orf72-mutant-rna-by-single-stranded-silencing-rnas
#18
Jiaxin Hu, Frank Rigo, Thazha P Prakash, David R Corey
Mutations within the chromosome 9 open reading frame 72 (c9orf72) gene are associated with both familial amyotrophic lateral sclerosis and frontotemporal dementia. The mutation leads to an expanded GGGGCC hexanucleotide repeat within the first intron of c9orf72 and an expanded CCCCGG repeat within a corresponding antisense transcript. Both the mutant intronic and antisense RNAs have been implicated in disease. We have previously reported that duplex RNAs complementary to the repeats can recognize disease-causing RNA and block detection of nuclear foci formed by the mutant transcripts...
December 22, 2016: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28003732/regulation-of-photoreceptor-gene-transcription-via-a-highly-conserved-transcriptional-regulatory-element-by-vsx-gene-products
#19
Yi Pan, Daniel F Comiskey, Lisa E Kelly, Dawn S Chandler, Heithem M El-Hodiri
PURPOSE: The photoreceptor conserved element-1 (PCE-1) sequence is found in the transcriptional regulatory regions of many genes expressed in photoreceptors. The retinal homeobox (Rx or Rax) gene product functions by binding to PCE-1 sites. However, other transcriptional regulators have also been reported to bind to PCE-1. One of these, vsx2, is expressed in retinal progenitor and bipolar cells. The purpose of this study is to identify Xenopus laevis vsx gene products and characterize vsx gene product expression and function with respect to the PCE-1 site...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27998711/progress-and-promise-of-antisense-oligonucleotide-therapeutics-for-central-nervous-system-diseases
#20
REVIEW
Kathie M Bishop
Antisense oligonucleotide (ASO) drugs are an emerging class of therapeutics that have recently demonstrated progress and promise to treat diseases of the central nervous system (CNS). ASOs for a variety of targets and mechanisms are currently being investigated in clinical trials and pre-clinically for a number of CNS diseases. This review examines the available data regarding central ASO delivery, distribution, pharmacokinetics, pharmacodynamics and therapeutic opportunities.
December 18, 2016: Neuropharmacology
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