Abstract: The present invention is directed to a method of modulating (e.g., inducing, inhibiting) activation of a double stranded RNA (dsRNA) signaling pathway, such as the dsRNA signaling pathway that accompanies RNA interference (RNAi) of a target RNA sequence, in a cell, comprising introducing into the cell small interfering RNA (siRNA) that degrades the target RNA sequence, and maintaining the cell under conditions in which RNAi of the target RNA sequence occurs and activation of the dsRNA signaling pathway is modulated in the cell.

Abstract: The present invention relates to a gene discovery system and gene expression systems specific for genes encoding ARE-containing mRNAs. In one aspect, the present invention relates to computational methods of selecting coding sequences of ARE-genes from databases using a one or more ARE search sequences. The ARE search sequences are from 10 to 80 nucleotides in length and comprise a sequence which is encompassed by one of the following two sequences: (a) WU/T(AU/TU/TU/TA)TWWW, SEQ ID NO. 1, wherein none or one of the nucleotides outside of the parenthesis is replaced by a different nucleotide, and wherein W represents A, U, or T; and (b) U/T(AU/TU/T/U/T)n, SEQ ID NO. 2 wherein n indicates that the search sequence comprises from 3 to 12 of the tetrameric sequences contained within the parenthesis. The method comprises extracting from the databases, those nucleic acids whose protein coding sequences are upstream and contiguous with a 3? untranslated region (UTR) that comprises one of the ARE search sequences.

Abstract: The present invention relates to a gene discovery system and gene expression systems specific for genes encoding ARE-containing mRNAs. In one aspect, the present invention relates to computational methods of selecting coding sequences of ARE-genes from databases using aone or more ARE search sequences. The ARE search sequences are from 10 to 80 nucleotides in length and comprise a sequence which is encompassed by one of the following two sequences: (a) WU/T(AU/TU/TU/TA)TWWW, SEQ ID NO. 1, wherein none or one of the nucleotides outside of the parenthesis is replaced by a different nucleotide, and wherein W represents A, U. or T; and (b) U/T(AU/TU/T/U/T)n, SEQ ID NO. 2, wherein n indicates that the search sequence comprises from 3 to 12 of the tetrameric sequences contained within the parenthesis. The method comprises extracting from the databases, those nucleic acids whose protein coding sequences are upstream and contiguous with a 3?untranslated region (UTR) that comprises one of the ARE search sequences.

Abstract: Mammalian somatic cells having a homozygous disruption in the gene which encodes the endonbonuclease RNase L and a homyzgous disruption in the gene which encodes the double-stranded RNA dependent kinase PKR are provided. Methods for producing enhanced levels of recombinant proteins in mammalian cell systems are also provided. In one aspect the method employs cells having a homozygous disruption in the RNase L gene and a homozygous disruption in the PKR gene and comprises transfecting the cells with a nucleic acid, or polynucleotide, encoding a desired, exogenous protein; expressing the exogenous protein in the cell; and isolating the exogenous protein from the transfected cells. In another aspect the method employs RNase L null cells transfected with a nucleic acid encoding a desired, exogenous protein. In another aspect the methods employ mutant cells hating a homozygous disruption in the PKR gene, i.e. PKR null cells.

Abstract: The present invention relates to a gene discovery system and gene expression systems specific for genes encoding ARE-containing mRNAs. In one aspect, the present invention relates to computational methods of selecting coding sequences of ARE-genes from databases using a one or more ARE search sequences. The ARE search sequences are from 10 to 80 nucleotides in length and comprise a sequence which is encompassed by one of the following two sequences: (a) WU/T(AU/TU/TU/TA)TWWW, SEQ ID NO. 1, wherein none or one of the nucleotides outside of the parenthesis is replaced by a different nucleotide, and wherein W represents A, U. or T; and (b) U/T(AU/TU/T/U/T)n, SEQ ID NO. 2, wherein n indicates that the search sequence comprises from 3 to 12 of the tetrameric sequences contained within the parenthesis.

Abstract: Mammalian somatic cells having a homozygous disruption in the gene which encodes the endoribonuclease known as RNase L and a homyzgous disruption in the gene which encodes the double-stranded RNA dependent kinase known as PKR. Methods for producing enhanced levels of recombinant proteins, or polypeptides, in mammalian cell systems are also provided. In one aspect the method employs cells having a homozygous disruption in the RNase L gene and a homozygous disruption PKR gene and comprises transfecting the cells with a nucleic acid, or polynucleotide, encoding a desired, exogenous protein, or polypeptide; expressing the exogenous protein in the cell; and isolating the exogenous protein from the transfected cells. In another aspect the method employs RNase L null cells transfected with a nucleic acid encoding a desired, exogenous protein.

Abstract: Methods and model systems for identifying and characterizing new therapeutic agents, particularly proteins, which mimic or inhibit the activity of all interferons, Type I interferons, IFN-&agr;, IFN-&bgr;, or IFN-&ggr;. The method comprises administering an interferon selected from the group consisting of IFN-&agr;, IFN &bgr;, IFN-&tgr;, IFN-&ohgr;, IFN-&ggr;, and combinations thereof to cultured cells, administering the candidate agent to a duplicate culture of cells; and measuring the effect of the candidate agent and the interferon on the transcription or translation of one or, preferably, a plurality of the interferon stimulated genes or the interferon repressed genes (hereinafter referred to as “ISG's” and “IRGs”, respectively). The model system is an array with gene probes that hybridize with from about 100 to about 5000 ISG and IRG transcripts.