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.

TY - JOUR. T1 - Phase II study of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C alpha, in patients with previously treated low-grade non-Hodgkins lymphoma. AU - Rao, S.. AU - Watkins, D.. AU - Cunningham, D.. AU - Dunlop, D.. AU - Johnson, P.. AU - Selby, P.. AU - Hancock, B.W.. AU - Fegan, C.. AU - Culligan, D.. AU - Schey, S.. AU - Morris, T. AU - Lissitchkov, T.. AU - Oliver, J.W.. AU - Holmlund, J.T.. PY - 2004/1. Y1 - 2004/1. N2 - Background: The purpose of this study was to assess the efficacy and safety of ISIS 3521, an antisense phosphorothioate oligonucleotide to protein kinase C in patients with relapsed low-grade non-Hodgkins lymphoma (NHL). Patients and methods: Twenty-six patients received ISIS 3521 (2 mg/kg/day) as a continuous infusion over 21 days of each 28-day cycle. Results: The median age of the patients was 53 years (range 37-77). Histological subtypes were low-grade follicular lymphoma (n=22) and B-cell small lymphocytic lymphoma (n=4). Twenty-one (81%) ...

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

Fingerprint Dive into the research topics of Phase II study of PKC-α antisense oligonucleotide aprinocarsen in combination with gemcitabine and carboplatin in patients with advanced non-small cell lung cancer. Together they form a unique fingerprint. ...

The pharmacokinetics of a 2′-O-(2-methoxyethyl)-ribose modified phosphorothioate oligonucleotide, ISIS 104838 (human tumor necrosis factor-α antisense), have been characterized in mouse, rat, dog, monkey, and human. Plasma pharmacokinetics after i.v. administration exhibited relatively rapid distribution from plasma to tissues with a distribution half-life estimated from approximately 15 to 45 min in all species. Absorption after s.c. injection was high (80-100%), and absorption after intrajejunal administration in proprietary formulations was as high as 10% bioavailability compared with i.v. administration. Urinary excretion of the parent drug was low, with less than 1% of the administered dose excreted in urine after i.v. infusion in monkeys at clinically relevant doses (≤5 mg/kg). ISIS 104838 is highly bound to plasma proteins, likely preventing renal filtration. However, shortened oligonucleotide metabolites of ISIS 104838 lose their affinity to bind plasma proteins. Thus, excretion of ...

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 ...

Inhibitory TLR7 and/or TLR9 oligonucleotides (inhibitory oligonucleotide [INH-ODN]) are characterized by a phosphorothioate backbone and a CC(T)XXX???GGG motif, respectively. INH-ODN 2088 is a prototypic member of this class of INH-ODN and acts as a TLR7 and TLR9 antagonist. It contains a G quadruple that leads to higher order structures by the formation of G tetrads. These structures are unfavorable for the prediction of their pharmacological and immunological behavior. We show in this study that modification of Gs within the G quadruple by 7-deaza-guanine or 7-deaza-2-O-methyl-guanine avoids higher order structures and improves their inhibitory potential. Whereas TLR9-induced TNF-? secretion of bone marrow-derived macrophages and conventional dendritic cells was equally inhibited by INH-ODN 2088 and G-modified INH-ODNs such as INH-ODN 24888, TLR7-induced TNF-? release and TLR7- and TLR9-induced IL-12p40 release were significantly more impaired by G-modified INH-ODNs. Similarly, the IL-6 ...

Phosphorothioate oligonucleotides (S-ODNs) have the ability to modulate gene expression selectively and thus have potential therapeutic capabilities. This potential led us to investigate the protein binding characteristics of selected S-ODNs. We evaluated S-ODN interactions with bovine serum albumin …

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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,

Drug stocks dip, with shares of Isis Pharmaceuticals plunging after it releases mixed Phase III clinical data for its cholesterol drug mipomersen.

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.

Isis Pharmaceuticals, Inc. Stock Trading Halted Today - read this article along with other careers information, tips and advice on BioSpace

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.. ...

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. ScholarBank@NUS 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

xlc compiler: export PATH=/usr/local/bin:/opt/freeware/bin:$PATH export OBJECT_MODE=64 export LIBICONV=/opt/freeware export CC=xlc_r -q64 export CFLAGS=-O -qstrict export CXX=xlC_r -q64 export CXXFLAGS=-O -qstrict export AR=ar -X64 export F77=xlf_r -q64 export CPPFLAGS=-I/afs/isis/pkg/libpng/include -I/usr/local/include -I$LIBICONV/include -I/usr/lpp/X11/include/X11 export LDFLAGS=-L/usr/local/lib -L$LIBICONV/lib -L/usr/lib -L/usr/X11R6/lib -lc ./configure --prefix=/afs/isis/pkg/grass-6.4.0 \ --enable-64bit \ --disable-shared \ --with-includes=/usr/include/fontconfig /usr/include/X11 /usr/include/X11/Xft /usr/include/X11/ext \ --x-includes=/usr/include/X11 \ --x-libraries=/usr/X11R6/lib \ --with-fftw-includes=/afs/isis/pkg/fftw-3.2.2/include \ --with-fftw-libs=/afs/isis/pkg/fftw-3.2.2/lib \ --with-gdal=/afs/isis/pkg/gdal/bin/gdal-config \ --with-proj-includes=/afs/isis/pkg/proj/include \ --with-proj-libs=/afs/isis/pkg/proj/lib \ --with-proj-share=/afs/isis/pkg/proj/share/proj \ ...

xlc compiler: export PATH=/usr/local/bin:/opt/freeware/bin:$PATH export OBJECT_MODE=64 export LIBICONV=/opt/freeware export CC=xlc_r -q64 export CFLAGS=-O -qstrict export CXX=xlC_r -q64 export CXXFLAGS=-O -qstrict export AR=ar -X64 export F77=xlf_r -q64 export CPPFLAGS=-I/afs/isis/pkg/libpng/include -I/usr/local/include -I$LIBICONV/include -I/usr/lpp/X11/include/X11 export LDFLAGS=-L/usr/local/lib -L$LIBICONV/lib -L/usr/lib -L/usr/X11R6/lib -lc ./configure --prefix=/afs/isis/pkg/grass-6.4.0 \ --enable-64bit \ --disable-shared \ --with-includes=/usr/include/fontconfig /usr/include/X11 /usr/include/X11/Xft /usr/include/X11/ext \ --x-includes=/usr/include/X11 \ --x-libraries=/usr/X11R6/lib \ --with-fftw-includes=/afs/isis/pkg/fftw-3.2.2/include \ --with-fftw-libs=/afs/isis/pkg/fftw-3.2.2/lib \ --with-gdal=/afs/isis/pkg/gdal/bin/gdal-config \ --with-proj-includes=/afs/isis/pkg/proj/include \ --with-proj-libs=/afs/isis/pkg/proj/lib \ --with-proj-share=/afs/isis/pkg/proj/share/proj \ ...

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,...

The raid that ended in the death of ISIS leader Abu Bakr al-Baghdadi was named after American aid worker Kayla Mueller, who was abducted by ISIS in 2013 and was killed in 2015. Ali Velshi talks with her parents, Carl and Marsha Mueller, about Baghdadis death and their mission to bring their daughter home.

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.

19/09/20: Read 3 experiences of students at ISIS ROSMINI in , Italy.Ratings: Overall: 4.22/5 - Teaching: 4.00/5 - Location: 5.00/5 - Atmosphere: 4.00/5 - Service: 4.33/5

An increasing number of biological and epidemiological evidence suggests that c.919-2A | G and c.2168A | G variants of solute carrier family 26, member 4 (SLC26A4) gene play a critical role in the development of large vestibular aqueduct syndrome (LVAS). In this study, we developed a rapid genotyping method for discriminating LVAS-associated high-frequency variants in SLC26A4 gene. The genotyping technique consists of 3′ terminal exonuclease-resistant phosphorothioate-modified allele specific primer extension mediated by exo+ polymerase. In PCR amplification by Pfu polymerase, allelic specific primers perfectly matching wild type allele were extended while no specific products were yielded from primers targeting variant allele. Similarly, allelic specific primers perfectly matching variant allele were extended and no specific products were observed from primers targeting wild type allele. The clinical application of 3′ terminal phosphorothioate-modified allele specific primer extension mediated by

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.

U.S. officials say new figures on oil revenues of the Islamic State of Iraq and Syria (ISIS) are more accurate than previous estimates. The new figures suggest ISIS receives about $100 million a year. NBC reports that the revenues are three times as much as previously thought, but thats not really true. A 2014 estimate…

GlaxoSmithKline has chosen to advance another programme under its alliance with US-based group Isis Pharmaceuticals to develop RNA therapeutics for rare diseases. - News - PharmaTimes

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...

ISIS is undeniably talented. Despite our unwavering endeavors to demolish the group, we have not. Although our efforts have significantly impeded some of ISISs…

Months after ISIS was pushed out of Palmyra, the extremist group is again fighting for the Syrian city in the face of heavy air strikes by Russias military.

The Iraqi-born ISIS leader, a scholar who spent four years in U.S. captivity, uses Islamic law to justify his ruthlessness, but he still enjoys soccer and fancy watches.

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If were not prepared to devise a coherent strategy aimed at defeating ISIS, then no amount of advisors or air strikes will make a difference in the long run. ISIS will simply watch and wait.

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.

Some Muslims in the Middle East insist the Islamic State is an Israeli-funded project despite any evidence that would suggest that.