Silencing of microRNAs in vivo with "antagomirs"
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE3425 | GEO | 2005/11/02
SECONDARY ACCESSION(S): PRJNA93459
REPOSITORIES: GEO
Similar Datasets
Project description:Using a novel class of chemically-engineered oligonucleotides, termed "antagomirs", we studied the biological significance of silencing miR-122 in the liver of mice at the mRNA level Experiment Overall Design: Mice were injected on three subsequent days with antagomir-122 or scrambled control (mm-antagomir-122), respectively; 80mg/kg bodyweight/day. 24 hrs after the last treatment, mice were sacrificed and total RNA isolated from the livers. RNA from three mice was pooled and used for generation of biotin-labelled cRNA.
2008-06-12 | E-GEOD-3425 | biostudies-arrayexpress
Project description:c57BL/6J female mice treated with LNA-antimiR's against miR-122.
2011-07-05 | E-MEXP-2802 | biostudies-arrayexpress
Project description:The tooth is derived from both the ectoderm and the neural crest (ectomesenchyme). It is often used as a model for studies of the basic mechanisms of organ development, including differentiation, cellular interaction, morphogenesis, and mineralization of extracellular matrices. In mouse, tooth development begins at embryonic day 11.5 (E11.5) by thickening of the dental epithelium, whereas mineralization of enamel and dentin in first molars starts at postnatal day 0 (P0). Tooth development entails a multistep and complex process of gene expression. Studies with genetically modified mice have contributed substantially to our understanding of genes that regulate tooth development and morphology. MicroRNAs (miRNA) are a class of non-coding RNAs that regulate gene expression at a post-transcriptional level, and are considered as important regulatory molecules during foetal development. By binding to target mRNAs, miRNA induce mRNA decay or translation repression. Recent bioinformatic predictions of miRNA targets in vertebrates indicate that hundreds of miRNAs are responsible for regulation of expression of up to 30% of the human protein-coding genes. Recent experiments has verified that miRNAs can regulate expression of hundreds of mRNAs in cultured cells. Previous study has also shown that microarrays can be used to detect physiologically relevant effects of miRNAs on expression of mRNAs in vertebrates; miRNAs have been shown to alter expression of a greater number of transcripts than previously appreciated, primarily through interaction with 3M-4UTRs. Understanding the biological function of miRNAs require knowledge of their mRNA targets. Bioinformatic approaches have been used to predict mRNA targets, among which both transcription factors and pro-apoptopic genes were prominent candidates. The precise molecular function of miRNAs remains largely unknown and a better understanding may require loss-of-function studies in vivo. It has been shown that intravenous administration of a novel class of chemically engineered oligonucleotides termed M-^SantagomirsM-^T resulted in a marked reduction of corresponding miRNA levels in most tissues. This resulted in upregulated expression of hundreds of genes predicted to be repressed by miR-122 because these genes had a miR-122 recognition motif in their 3M-4UTR region. Paradoxically, antagomir treatment also revealed a significant number of downregulated genes that may be activated by miR-122. The mechanism by which miRNAs may activate gene expression in vivo is unknown. However, it may involve an indirect effect (the suppression of a transcriptional repressor), or alternatively, miRNA may have a direct effect on gene activation (e.g. chromatin remodeling). Studies of microRNA expression profiles of the developing murine molar tooth germ have shown these to be highly dynamic, some miRNAs being abundantly expressed during the early development of the molar tooth germ, while others are highly expressed only at later developmental stages. A recent study also suggested that miRNAs modulate tooth morphogenesis and ameloblast differentiation, perhaps largely by fine tuning conserved signaling networks. The function of microRNA-214 (miR-214) is unknown, however, it has been related to normal growth and skeletal development in mice. In tooth germs miR-214 is more highly expressed during later developmental stages. It was selected as a target for silencing using anti-miR-214. Here we report effects from injections of 1-100 pmol of anti-miR-214 close to developing first mandibular molar in newborn mice. At 24 hrs, or more, after injection significant changes in gene expression, and in levels of several correspondingly encoded proteins, were found in the tooth germ.
2011-08-31 | E-MTAB-357 | biostudies-arrayexpress
Project description:To determine the effect of antimiR-122 administration on the mouse miRNome. To functionally investigate a possible link between miR-122 and iron metabolism we inhibited miR-122 by a single, intraperitoneal injection of Locked Nucleic Acid (LNA)-modified antimiR oligonucleotides into age- and sex-matched C57Bl/6 WT mice. To inhibit miR-122 specifically, we injected an antimiR compound with perfect complementarity to miR-122 [perfect match (PM); PM_antimiR-122]. As negative controls, mice were either injected with an LNA control compound with two mismatches (2MM, 2MM_antimiR-122) or the vehicle control (SAL; 0.9% NaCl). Mice were sacrificed three and six weeks after injection. Independent of treatment, mice were viable and exhibited no overt physical or behavioral abnormalities. To exclude that PM_antimiR-122 administration disturbs the expression of other miRNAs we analyzed miRNA expression profiles in the livers, hearts and spleens of the same mice.
2010-10-20 | E-GEOD-24786 | biostudies-arrayexpress
Project description:Quantitative proteomic analysis raw data for the manuscript entitled “Chemically Engineered Antibodies for Autophagy-based Receptor Degradation”.
2024-10-12 | PXD056766 |
Project description:To realize a carbon-neutral bioeconomy, the concept of electrobiocatalysis has been developed, in which CO2 is first chemically reduced to formate and subsequently assimilated by enzymatic cascades or engineered microbes. A key step in the assimilation of formate is its reduction into formaldehyde, which is chemically challenging. Here, we developed a two-enzyme route in which formate is activated into formyl phosphate and reduced by NAD(P)H into formaldehyde. Exploiting the promiscuity of acetate kinase and N-acetyl--glutamyl phosphate reductase, we demonstrate the phosphate (Pi) route in vitro and in vivo. We further engineered a formyl phosphate reductase variant with improved formyl phosphate conversion in vivo by suppressing cross-talk with native metabolism. We further show that the Pi route can be interfaced with a recently developed formaldehyde assimilation pathway (FORCE pathway) to provide a thermodynamically and kinetically highly efficient route from formate into C2-compounds.
2023-03-22 | MSV000091532 | MassIVE
Project description:RNA interference (RNAi)-based gene therapy has great potential in cancer and infectious disease treatment to correct abnormal up-regulation of gene expression. We show a new original method uses synthetic microRNAs combined with a thermo-inducible promoter to reduce specific gene expression. The targeted gene is the luciferase firefly reporter gene overexpressed in a subcutaneous tumor which allows the RNAi monitoring by bioluminescence imaging (BLI). The inducible inhibition was first demonstrated in vitro using genetically modified cells lines and then in vivo using the corresponding xenograft model in mice. Achieving spatio-temporal control, we demonstrate the feasibility to induce, in vivo, a specific gene inhibition on demand. Future applications of this RNAi-based gene therapy, which can be restricted to pathological tissue, would offer wide-ranging potential for disease treatment.
| S-EPMC5856835 | biostudies-literature
Project description:Gene expression profiling of HCCs developed in miR-122 knockout mice compared to age-matched wild type mice. The significance of our study is that miR-122 knockout mice spontaneously develop liver tumors and the gene expression profile demonstrated dysregulation of several pathways involved in liver disease and HCC.
2012-08-07 | GSE31731 | GEO
Project description:Chemically Engineered Antibodies for Autophagy-based Receptor Degradation
| PRJNA1172119 | ENA
Project description:modENCODE_submission_458 This submission comes from a modENCODE project of Robert Waterston. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: Our experiments are designed to detect all C. elegans transcripts by hybridizing RNA to commerically available genome tiling arrays. To maximize the chances of detecting rare transcripts with limited expression in specific cells, we are extracting RNA from selected embryonic cells isolated by FACS and from postembryonic cells by use of the mRNA tagging method. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Keywords: Transcript tiling array analysis EXPERIMENT TYPE: Transcript tiling array analysis. BIOLOGICAL SOURCE: Strain: TV1112 (engineered, target gene unc-122 tagged by RFP); Tissue: coelomocytes; Developmental Stage: Mixed stage of embryos 20dC; Genotype: wyIs58 (opt-3::GFP::RAB-3; unc-122::RFP); Sex: Hermaphrodite; NUMBER OF REPLICATES: 3; EXPERIMENTAL FACTORS: Strain TV1112 (engineered, target gene unc-122 tagged by RFP); temperature 20; Developmental Stage Mixed stage of embryos 20dC; Tissue coelomocytes
2010-08-04 | E-GEOD-23248 | biostudies-arrayexpress