Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids. In general, the compounds are phosphorothioate oligonucleotides wherein the 5′-terminal internucleoside linkage or the 5′- and 3′-terminal linkages are modified.
Figure 1. ODN2395 binding to platelets and induction of platelet activation, aggregation, and adhesion. (a) ODN2395 was incubated with platelets and binding was assessed (***, P , 0.001 vs. background [BG], 10 µM non-PS-modified ODN2395 ["ODN2395 nonmod"], and 50 nM ODN2395; n = 6). (b) CD62P surface expression after ODN2395 incubation of human washed platelets compared with unstimulated control samples and ODN2395 nonmod (*, P , 0.05 vs. unstimulated/1-10 µM ODN2395 nonmod/50 nM ODN2395; ***, P , 0.001 vs. unstimulated/1-10 µM ODN2395 nonmod/50 nM ODN2395; n = 5). (c) Platelet aggregation after 5 µM ODN2395 stimulation of PRP; final aggregation compared with 5 µM ADP/1 µg/ml collagen stimulation; representative aggregation curves (n = 6). (d) Murine GPIIb/IIIa activation after incubation with ODN2395 (1 µM/5 µM; *, P , 0.05/***, P , 0.001 vs. unstimulated WT/TRL9−/−; n = 4-5) detected on platelets from WT or mice deficient in TLR9 (TRL9−/−) using a single chain antibody ...
Baker IDI Heart and Diabetes Institute, St. Vincents Institute of Medical Research, and Bio21 Institute, University of Melbourne, Melbourne, Victoria 3010, AustraliaBaker IDI Heart and Diabetes Institute, St. Vincents Institute of Medical Research, and Bio21 Institute, University of Melbourne, Melbourne, Victoria 3010, Australia ...
Sequence-specific phosphorothioate oligonucleotides comprising nucleoside units which are joined together by either substantially all Sp or substantially all Rp phosphorothioate intersugar linkages ar
The present invention discloses novel methods and compositions useful for removing toxic heavy metals from a host organism containing detectable levels of such heavy metals. The method comprises administering to the host organism a therapeutically effective amount of a heavy-metal binding agent which, when saturated with heavy metal atoms, is readily excreted from the body. In a preferred embodiment of the present invention, the binding agent is an oligomeric phosphorothioate oligonucleotide.
BACKGROUND: Long oligonucleotide microarrays are potentially more cost- and management-efficient than cDNA microarrays, but there is little information on the relative performance of these two probe types. The feasibility of using unmodified oligonucleotides to accurately measure changes in gene expression is also unclear.. RESULTS: Unmodified sense and antisense 70-mer oligonucleotides representing 75 known rat genes and 10 Arabidopsis control genes were synthesized, printed and UV cross-linked onto glass slides. Printed alongside were PCR-amplified cDNA clones corresponding to the same genes, enabling us to compare the two probe types simultaneously. Our study was designed to evaluate the mRNA profiles of heart and brain, along with Arabidopsis cRNA spiked into the labeling reaction at different relative copy number. Hybridization signal intensity did not correlate with probe type but depended on the extent of UV irradiation. To determine the effect of oligonucleotide concentration on ...
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Trying to complete the Isis Blood Code? Our Guide to the Code Vein Isis Vestige locations will help make this task a lot quicker.
Isis Pharmaceuticals, Inc. (Nasdaq: ISIS), the leader in antisense therapeutics, today announced that management will present a company overview at Goldman Sachs 31st Annual Global
ISIS-FGFR4Rx to Treat ObesityCARLSBAD, Calif., Jan. 6, 2011 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced today that it has added two new drugs to its development pipeline,
This article answers the question about the difference between ISIS and ISIl . It provides a comprehensive look at how they became a powerful force and causes of sectarian conflict in the Mid-East.
When I look at Isis there I can just hear the purr. I would bet if you buried that little mic right between her front paws in that shot, you would get a great 25-50Hz rumble that would do a little sub-woofer proud. Im assuming shes grown accustom to the presence of microphones in her world by this time.. ...
Isis Pharmaceuticals, Inc. Stock Trading Halted Today - read this article along with other careers information, tips and advice on BioSpace
L-lysyl-L-threonyl-L phenylalanyl-N-3-carboxypropyl)-glycine amide, acetate salt. 5) Treatment of perinatal asphyxia - Allopurinol sodium. 6) Treatment of Duchenne muscular dystrophy - Exon 52 specific phosphorothioate oligonucleotide. 7) Treatment of Duchenne muscular dystrophy - Exon 55 specific phosphorothioate oligonucleotide. 8) Treatment of malaria - Artesunate. 9) Treatment of chronic lymphocytic leukaemia - 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide. 10) Treatment of very-long-chain-acyl-CoA dehydrogenase deficiency - Triheptanoin. 11) Treatment of long-chain L-3-hydroxyacyl-CoA-dehydrogenase deficiency - Triheptanoin. 12) Treatment of chronic lymphocytic leukaemia - Humanised single chain monoclonal antibody against CD37. 13) Treatment of non-infectious uveitis - Voclosporin. Copyright © 2012-2013, Orphan Druganaut Blog. All rights ...
TY - JOUR. T1 - Phosphorothioate-modified oligodeoxynucleotides inhibit human cytomegalovirus replication by blocking virus entry. AU - Luganini, Anna. AU - Caposio, Patrizia. AU - Landolfo, Santo. AU - Gribaudo, Giorgio. PY - 2008/3. Y1 - 2008/3. N2 - Studies in animal models have provided evidence that Toll-like receptor 9 (TLR9) agonists, such as synthetic oligodeoxynucleotides (ODNs) that contain immunostimulatory deoxycytidyl-deoxyguanosine (CpG) motifs (CpG ODNs), protect against a wide range of viral pathogens. This antiviral activity has been suggested to be indirect and secondary to CpG-induced cytokines and inflammatory responses triggered through TLR9 activation. However, few studies have addressed the potential of CpG ODNs as direct antiviral agents. Here, we report on the ability of some CpG ODNs to directly suppress, almost completely, human cytomegalovirus (HCMV) replication in both primary fibroblasts and endothelial cells. Murine CMV replication was inhibited as well, whereas no ...
An improved delivery system for antisense oligonucleotides involves a liposomal composition, comprising a liposome which consists essentially of neutral phospholipids and an antisense oligonucleotide that is entrapped in the liposome and is selected from the group consisting of phosphodiester oligonucleotides, phosphorothioate oligonucleotides, and p-ethoxy oligonucleotides.
Almsherqi, Z.A., Deng, Y., Kohlwein, S.D. (2006). Cubic membranes: A legend beyond the Flatland* of cell membrane organization. Journal of Cell Biology 173 (6) : 839-844. [email protected] Repository. https://doi.org/10.1083/jcb. ...
Angiozyme: nuclease-stabilized ribozyme with phosphorothioate linkages developed against VEGF-receptor subtype Flt-1 mRNA for use as an angiogenesis inhibitor; base sequence given in first source
Gemalto annonce avoir été choisi par Isis pour le déploiement de paiement mobile et de services NFC aux États-Unis. Isis a donc retenu la solution Allynis Trusted Service Manager (TSM) de Gemalto pour sécuriser sa plateforme de commerce mobile. Isis,...
Researchers for Genzyme (GENZ) and Isis Pharmaceuticals (ISIS) trumpeted the success of their cholesterol drug mipomersen in a late-stage trial, but investors heard a sour note when the side affects
Health,...- Conference Call Webcast Thursday May 7 08:30 a.m. EDT at ...CARLSBAD Calif. May 7 /- Isis Pharmaceuticals... ...,Isis,Reports,Strong,Financial,Results,and,Highlights,for,First,Quarter,of,2009,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Isis Pharmaceuticals announces plans to provide details regarding its late-stage pipeline, and also extends its gains following yesterdays development milestone.
Prosecutors say three people suspected of supporting the ISIS group and thought to have been planning an attack in Europe were arrested earlier this year.
Reports from Australia indicate a disturbing number of doctors and nurses have chosen to support ISIS, as summarized by Albawaba News from the Australian Daily Telegraph.
eBiochemicals provides information on the O,O-Bisisopropyl O-(4-(methylsulfinyl)phenyl) phosphorothioate(O,O-diisopropyl O-(4-(methylsulfinyl)phenyl) phosphorothioate): structure, NMR,MS,IR,spectral data, msds, molecular formula, cas, physical and chemical properties, and suppliers.
Kurdish forces in Syria found cocaine in the home of a slain ISIS commander, sparking further rumors that militants are using narcotics to cope with the effects of battle. ISIS leader Emir Abu...
The Iraqi government is working to keep jihadist group the Islamic State of Iraq and Syria (ISIS) from taking Baghdad, but terrorist expert Arnaud de Borchgrave says it looks doubtful that Iraq will be able to keep ISIS from reaching the capital city.
An onslaught of ISIS attacks in recent days has suddenly pushed more than 130,000 Syrian Kurdish refugees into Turkey-which has already taken in more t ...
A recently unsealed affidavit alleges that U.S. citizen Mohamed Elshinawy pledged allegiance to ISIS and received about $8,700 from the terrorist...
After Kurdish forces pushed Islamic State militants back from the embattled Mount Sinjar in northwestern Iraq, they returned home only to find devastation. RT traveled to the region to see how people are coping with the scars that war has left behind.
The potential for therapeutic application of splice-switching oligonucleotides (SSOs) to modulate pre-mRNA splicing is increasingly evident in a number of diseases. However, the primary drawback of this approach is poor cell and in vivo oligonucleotide uptake efficacy. Biological activities can be significantly enhanced through the use of synthetically conjugated cationic cell penetrating peptides (CPPs). Studies to date have focused on the delivery of a single SSO conjugated to a CPP, but here we describe the conjugation of two phosphorodiamidate morpholino oligonucleotide (PMO) SSOs to a single CPP for simultaneous delivery and pre-mRNA targeting of two separate genes, exon 23 of the Dmd gene and exon 5 of the Acvr2b gene, in a mouse model of Duchenne muscular dystrophy. Conjugations of PMOs to a single CPP were carried out through an amide bond in one case and through a triazole linkage (click chemistry) in the other. The most active bi-specific CPP-PMOs demonstrated comparable exon skipping levels
2010) Splice-switching as a treatment for duchenne muscular dystrophy. In: Pathology Update 2010. Royal College of Pathologists Australasia, 26 - 28 February 2010, Melbourne, Australia. ...
Cu2+ is a very important metal ion in biology, environmental science, and industry. Developing biosensors for Cu2+ is a key topic in analytical chemistry. DNAzyme-based sensors are highly attractive:, for their excellent sensitivity, stability, and programmability, In the past decade, a few Cu2+ biosensors were reported using DNAzymes with DNA cleavage or DNA ligation activity. However, they require unstable ascorbate or imidazole activation. So far, no RNA cleaving DNAzymes specific for Cu2+ are known. In this work, a phosphorothioate (PS) RNA-containing library was used for in vitro selection, and a few new Cu2+-specific RNA-cleaving DNAzymes were isolated. Among them, a DNAzyme named PSCu10 was studied further. It has only eight nucleotides in the enzyme loop with a cleavage rate of 0.1 min(-1) in the presence of 1 mu M Cu2+ at pH 6.0 (its optimal pH). Between the two diastereomers of the PS RNA chiral center, the R-p isomer is 37 times more active than the S-p one. Among the other divalent ...
Yes, of course, we have to circle around to Isis, for Isis is a formidable Scorpion Goddess Herself. In this guise, She is called Iset Ta-Wahaet, Isis the Scorpion. In other texts, Isis is joined with Serket Hetyt, the Scorpion Goddess, She Who Casues the Throat to Breathe, as Isis-Serket. (It is interesting to note…
Many questions remain after the Paris attacks, but one thing is clear-- ISIS is becoming increasingly difficult for authorities to track. In recent years, ISIS has recruited individuals in Syria, Iraq and abroad, many of whom have become radicalized. The
Dinucleoside phosphorodithioate phosphoramidite precursors useful in the synthesis of oligonucleotide phosphorodithioate which can be used as antisense inhibitors of translation.
Antisense oligos containing phosphorothioate bonds can be used in medium containing serum. However, it is recommended that you inactivate the exonucleases in the serum to decrease the chances of degredation even when protecting modifications (such as phosphorothioate bonds) are present. Exonuclease inactivation can be accomplished by heat inactivatation at 65°C (instead of 56°C) for 30 minutes. The half life of such an antisense oligo will be dependent on the target transcript, the cell type, and the antisense construct, resulting in no set average for this number. There are reports of antisense oligos lasting 24 hours in vivo (mice ...
From M A Navigator (January 12, 2011) Stanley Crooke, the chief executive of US drug developer Isis Pharmaceuticals (NASDAQ ISIS), expects that French drug make
Drug developer Isis Pharmaceuticals Inc. and partner Genzyme said Thursday a panel of advisers to the Food and Drug Administration had voted 9 to 6 to recommend approval of Kynamro, for treating patients genetically predisposed to have sky-high LDL, or bad cholesterol. The FDA is not bound to follow recommendations of its advisers, but usually does so.
For the first time, the United States launches manned airstrikes from a base in Turkey against ISIS forces in Syria, the Pentagon said.
See an archive of all isis stories published on the New York Media network, which includes NYMag, The Cut, Vulture, and Grub Street.
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A simple method for the configurational analysis of the four major 2-deoxynucleoside 5-[160, 180] phosphorothioates, (1), and adenosine 5-[160, 180] phosphorothioate, (1a), is described. The method involves permethylation of (1,1a) with diazomethane or dimethyl sulphate, to generate the corresponding S-methyl-O-methyl phosphorothioate, (2,2a), 8P(3:1 DMF:d4-MeOH) +30ppm. Having assigned the diastereoisomers of (2,2a) to their corresponding 31P.n.m.r. resonances, the 18O-isotope is located by examination of 31P(180) isotope shifts. A larger shift, (0.05ppm), is observed on the diastereoisomer with 180 in the P-O position than in the P-OMe position, (0.02ppm). Configurations of (2,2a) were assigned by partial hydrolysis of the Sp diastereoisomer of a 1:1 mixture of the diastereoisomers of 2-deoxyribonucleoside- or adenosine 5-O-methyl phosphorothioate diester, (3,3a), 8P(3:1 DMF:d4-MeOH) +58ppm, by snake venom phosphodiesterase. Subsequent methylation of (3,3a) yielded correspondingly ...
Question 2: Can we predict the liver injury in humans using toxicogenomics data from animals. Around 40% of drug-induced liver injury (DILI) cases are not detected in the preclinical studies using the conventional indicators (such as pathology, clinical chemistry data). It has been hypothesized that genomic biomarkers will be more sensitive than conventional markers in detecting human hepatotoxicity signals in preclinical studies (i.e., in vitro and in vivo assays). In this project, we provide the human hepatotoxicity data for most of the drugs (the last three columns in the table named "Drug Information"). The contests can explore the possibility of predicting the DILI potential in humans using the in vitro data from rat primary hepatocytes or human primary hepatocytes, or the animal data from two different treatment protocols. Alternatively, these data can also be combined to enhance the predictive power for the human hepatotoxic potential ...
Isis Pharmaceuticals has announced positive Phase II results in patients with Type 2 diabetes treated with ISIS 113715 as a single-agent. An intent-to-treat analysis of all patients enrolled in the trial treated with 200 mg/wk for three months showed statistically significant improvement in multiple measures of glucose control. ISIS 113715 did not cause hypoglycemia (low blood sugar), did not cause weight gain and was well tolerated. ISIS 113715, a second-generation antisense drug, is a novel insulin sensitizer that reduces the expression of protein tyrosine phosphatase-1B (PTP-1B). PTP-1B is a mediator of insulin resistance, one of two main defects in patients with Type 2 diabetes. ...
Jordan promptly announced that it would execute the six ISIS terrorists in its custody.. To a greater degree even than al Qaeda, ISIS has become an international symbol of pure evil. It carries on a constant recruiting campaign among the worlds Muslims, and while most, of course, are repelled by the groups outrages, some are not. The territory ISIS controls has become a magnet for the demented, the power-mad and the simply evil. Its adherents are being sent back to their home countries around the world to pursue jihad. ISIS wants to rule the world. It wont succeed in that objective, and one would think that an organization so crazed and so ill-attuned to the realities of governance must be inherently unstable, and cant cohere for long. Perhaps that is right, but in the meantime, grave damage is being done.. Evil thrives where it is seen to prosper. It is success, not failure, that draws converts. To millions around the world, ISIS is triumphant, its enemies defeated and humiliated. The only ...
Throne." Egyptian mother goddess. Isis has many names: "Mistress of Magic,The Queen of Heaven (similar to Astarte), The Great Lady, the God-Mother, lady of Re-a-nefer; Isis-Nebuut, Lady of Sekhet; Lady of Besitet; Isis in Per Pakht, the Queen of Mesen; Isis of Ta-at-nehepet; Isis, dweller in Netru; Isis, Lady of Hebet; Isis in P-she-Hert; Isis, Lady of Khebt; Usert-Isis, Giver of Life, Lady of Abaton, Lady of Philae and Lady of the Countries of the South." Isis ruled over all matters concerning mothering, life, and sorcery. She was the daughter of Geb and Nut, according to the Heliopolitan genealogy, sister-wife of Osiris and, according to most myths, the mother of Horus. As the personification of the throne, Isis was an important source of the Pharaohs power. Isis Latin epithet was Stella Maris, which means, "star of the sea." Isis was depicted in human form, crowned either by a throne or by cow horns enclosing a sun disk, occasionally a vulture was incorporated in her crown. She is also ...
Macherey-Nagel™ Nucleodur™ C18 Isis HPLC Column I.D.: 2mm; Length: 250mm; Particle Size: 3um Macherey-Nagel™ Nucleodur™ C18 Isis HPLC...
Micelární čistící roztok. Program TEEN DERM zahrnuje přípravky, které umožňují dokonalé a současně šetrné každodenní čištění mastné kůže, urychlují vymizení projevů akné a zabraňují jejich opětovnému vytvoření.