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To investigate the possible role of eukaryotic initiation factor 4E-binding protein-2 (4E-BP2) in metabolism and energy homeostasis, high-fat diet-induced obese mice were treated with a 4E-BP2-specific antisense oligonucleotide (ASO) or a control 4E-BP2 ASO at a dose of 25 mg/kg body wt or with saline twice a week for 6 wk. 4E-BP2 ASO treatment reduced 4E-BP2 levels by >75% in liver and white (...
CONTEXT The GH receptor (GHR) pseudoexon 6Psi defect is a frequent cause of GH insensitivity (GHI) resulting from a non-functioning GH receptor (GHR). It results in a broad range of phenotypes and may also be present in patients diagnosed as idiopathic short stature. OBJECTIVE Our objective was to correct aberrant GHR splicing and inclusion of 6Psi using exon-skipping antisense oligonucleotid...
Allele-specific oligonucleotide real-time quantitative PCR (ASO-RQPCR) is a standardized technique for detection and monitoring of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) but not multiple myeloma (MM) due to a low applicability inherent with presence of somatic hypermutation. Herein, by a staged PCR approach and sequencing, clonality and tumor-specific complementari...
Lipid droplets in the liver are coated with the perilipin family of proteins, notably adipocyte differentiation-related protein (ADRP) and tail-interacting protein of 47 kDa (TIP47). ADRP is increased in hepatic steatosis and is associated with hyperlipidemia, insulin resistance, and glucose intolerance. We have shown that reducing ADRP in the liver via antisense oligonucleotide (ASO) treatment...
OBJECTIVE The goal of this study was to determine the expression signature and the potential role of microRNAs in human arteries with arteriosclerosis obliterans (ASO). METHODS AND RESULTS The expression profiles of microRNAs in human arteries with ASO and in normal control arteries were determined by quantitative reverse transcription-polymerase chain reaction array. Among the 617 detected m...
The solvothermal reaction of n-BuSn(O)OH with PhPO(3)H(2) afforded the hexanuclear monoorganooxotin phosphonate cage, {[(n-BuSn)(3)(MeO)(3)O](2)(O(3)PPh)(4)}.MeOH 1. When the n-Bu(2)Sn(PhCO(2))(2) precursor reacted with PhPO(3)H(2) in a 1 : 1 stoichiometric ratio, the diorganotin phosphonate ladder [n-Bu(2)SnO(3)PPh](n) 2 was obtained. The reaction of [n-Bu(2)(PrO)Sn](2)O with 4-OH-3-NO(2)-C(6)...
The study was aimed at investigating the feasibility of using a poly (amidoamine) (PAMAM) dendrimer as a carrier for topical iontophoretic delivery of an antisense oligonucleotide (ASO). Bcl-2, an anti-apoptotic protein implicated in skin cancer, was used as the model target protein to demonstrate the topical gene silencing approach. Confocal laser scanning microscopy studies demonstrated that ...
MicroRNAs (miRNAs) are a class of 20-24 nt noncoding RNAs that regulate target mRNAs post-transcriptionally by binding with imperfect complementarity in the 3'-untranslated region (3'-UTR) and inhibiting translation or RNA stability. Current understanding of miRNA biology is limited, and antisense oligonucleotide (ASO) inhibition is a powerful technique for miRNA functionalization in vitro and ...
Antisense oligonucleotides (ASOs) with phosphorothioate (PS) linkages are broadly used as research tools and therapeutic agents. Chemically modified PS-ASOs can mediate efficient target reduction by site-specific cleavage of RNA through RNase H1. PS-ASOs are known to be internalized via a number of endocytotic pathways and are released from membrane-enclosed endocytotic organelles, mainly late ...
microRNAs (miRNAs) have been shown to play a role in cancer. Antisense oligonucleotides can bind directly to miRNAs and block their activity, which are generally named anti-miRNAs. To suppress A549 cell proliferation in vitro and in vivo by anti-miRNAs, an anti-miR-150 expression vector (PR-ASO-150), regulated by the H1 promoter and containing a '...
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