Search results for "Phosphorothioate Oligonucleotides"
showing 4 items of 4 documents
Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mi…
1996
Chronic intestinal inflammation induced by 2,4,6,-trinitrobenzene sulfonic acid (TNBS) is characterized by a transmural granulomatous colitis that mimics some characteristics of human Crohn's disease. Here, we show that the transcription factor NF-kappa B p65 was strongly activated in TNBS-induced colitis and in colitis of interleukin-10-deficient mice. Local administration of p65 antisense phosphorothioate oligonucleotides abrogated clinical and histological signs of colitis and was more effective in treating TNBS-induced colitis than single or daily administration of glucocorticoids. The data provide direct evidence for the central importance of p65 in chronic intestinal inflammation and …
Predominant role of NF-kappa B p65 in the pathogenesis of chronic intestinal inflammation.
1998
NF-kappa B is a key transcription factor of lymphocytes and macrophages with important regulatory functions in the immune system and inflammatory processes. These functions are at least partially based on its ability to regulate the promoters of a variety of genes whose products, such as cytokines, adhesion molecules and acute phase proteins, are critical for inflammatory processes. In the present study, we describe a method to treat established intestinal inflammation by local or systemic application of antisense phosphorothioate oligonucleotides targeting the translation start site of the p65 subunit of NF-kappa B. Specific downregulation of p65 by administration of antisense phosphorothi…
Antisense Phosphorothioate Oligonucleotides to the p65 Subunit of NF-κB Abrogate Fulminant Septic Shock Induced byS. typhimuriumin Mice
2001
The aim of this study was to characterize the functional relevance of the transcription factor NF-κB in the pathogenesis of septic shock. BALB/c mice were infected with two wild-type (WT 1, WT 2) strains of S. typhimurium that induce NF-κB or an escape variant that lacks this ability (P21) at a dose of 1 × 109/animal, respectively. Furthermore, wild-type infected mice were treated with antisense oligonucleotides directed against NF-κB 24 h before and 3 or 6 h after infection, while mismatched oligonucleotides were used as controls. Subsequently, the clinical course, histological and immunological alterations were monitored. Infection with WT 1 and WT 2 strains led to lethal septic shock wit…
Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune r…
2010
Vaccination with in vitro transcribed RNA coding for tumor antigens is considered a promising approach for cancer immunotherapy and has already entered human clinical testing. One of the basic objectives for development of RNA as a drug is the optimization of immunobioavailability of the encoded antigen in vivo. By analyzing the effect of different synthetic 5' mRNA cap analogs on the kinetics of the encoded protein, we found that m(2)(7,2'-O)Gpp(S)pG (beta-S-ARCA) phosphorothioate caps, in particular the D1 diastereoisomer, profoundly enhance RNA stability and translational efficiency in immature but not mature dendritic cells. Moreover, in vivo delivery of the antigen as beta-S-ARCA(D1)-c…