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Human rnase iii and compositions and uses thereofHuman rnase iii and compositions and uses thereof description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20090270486, Human rnase iii and compositions and uses thereof. Brief Patent Description - Full Patent Description - Patent Application Claims
The present application is a continuation of U.S. application Ser. No. 11/001,993 filed Dec. 2, 2004, which is a divisional of U.S. application Ser. No. 10/079,185 filed Feb. 20, 2002, which is a continuation-in-part of U.S. application Ser. No. 09/900,425 filed Jul. 6, 2001, U.S. Pat. No. 6,737,512. All of the above are assigned to the assignee of the present invention and are incorporated by reference herein in their entirety. The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled ISIS5030USC1SEQ.txt, created on Dec. 22, 2008 which is 36 Kb in size. The information in the electronic format of the sequence listing is incorporated herein by reference in its entirety. The present invention relates to a human RNase III, the gene for which has now been cloned and characterized, and compositions and uses thereof. Antisense inhibitors of human RNase III are also described. Ribonuclease III (RNase III) is an endoribonuclease that cleaves double stranded RNA. The enzyme is expressed in many organisms and is highly conserved. I. S. Mian, Nucleic Acids Res., 1997, 25, 3187-95. All RNase III species cloned to date contain an RNase III signature sequence and vary in size from 25 to 50 kDa. Multiple functions have been ascribed to RNase III. In both E. coli and S. cerevisiae, RNase III has been reported to be involved in the processing of pre-ribosomal RNA (pre-rRNA). Elela et al., Cell, 1996, 85, 115-24. RNase III has also been reported to be involved in the processing of small molecular weight nuclear RNAs (snRNAs) and small molecular weight nucleolar RNAs (snoRNAs) in S. cerevisiae. Chanfreau et al., Genes Dev. 1996, 11, 2741-51; Qu et al., Mol. Cell. Biol. 1996, 19, 1144-58. In E. coli, RNase III has also been reported to be involved in the degradation of some mRNA species. D. Court, in Control of messenger RVA stability, 1993, Academic Press, Inc, pp. 71-116. A human double strand RNase (dsRNase) activity has been described. Wu et al., J. Biol. Chem., 1998, 273, 2532-2542; Crooke, U.S. Pat. No. 5,898,031; U.S. Pat. No. 6,017,094. By the rational design and testing of chemically modified antisense oligonucleotides that contained oligoribonucleotide stretches of varying length, a dsRNase activity was demonstrated in human T24 bladder carcinoma cells which produced 5′-phosphate and 3′-hydroxyl termini upon cleavage of the complementary cellular RNA target. This pattern of cleavage products is a feature of E. coli RNase III. The cleavage activity in human cells required the formation of a dsRNA region in the oligonucleotide. This human dsRNase activity is believed to be useful as an alternative terminating mechanism to RNase H for antisense therapeutics. Because it relies on “RNA-like” oligonucleotides, which generally have higher potency than the “DNA-like” oligonucleotides required for RNase H activity, it may prove an attractive alternative to RNase H-based antisense approaches. RNA interference (RNAi) is a form of sequence-specific, post-transcriptional gene silencing in animals and plants, elicited by double-stranded RNA (dsRNA) that is homologous in sequence to the silenced gene. Elbashir et al., Nature, 2001, 411, 494-498. dsRNA triggers the specific degradation of homologous RNAs, only within the region of homology. The dsRNA is processed to 21- to 23-nucleotide fragments, sometimes called short interfering RNAs (siRNAs) which are believed to be the guide fragments for sequence-specific mRNA degradation. The processing of longer dsRNA to these short siRNA fragments is believed to be accomplished by RNase III. Elbashir et al., ibid., Elbashir et al., Genes and Devel., 2001, 15, 188-200. Thus it is believed that the human RNase III of the present invention may be useful in further understanding and exploiting the gene silencing mechanism, particularly in human cells. Despite the substantial information about members of the RNase III family and the cloning of genes encoding proteins with RNase III activity from a number of lower organisms (E. coli, yeast and others), no human RNase III has previously been cloned. This has hampered efforts to understand the structure of the enzyme(s), its distribution and the functions it may serve. The present application describes the cloning and characterization of a cDNA that expresses a human RNase III. Cloning and sequencing of the cDNA encoding human RNase III allowed characterization of this nucleic acid as well as of the location and function of the RNase III protein itself. The present invention provides a polynucleotide sequence (set forth herein as SEQ ID NO: 1) which has been identified as encoding human RNase III by the homology of the calculated expressed polypeptide (provided herein as SEQ ID NO: 2) with known amino acid sequences of yeast and worm RNase III as well as by functional analysis. The present invention provides polynucleotides that encode human RNase III, the human RNase III polypeptide, vectors comprising nucleic acids encoding human RNase III, host cells containing such vectors, antibodies targeted to human RNase III, nucleic acid probes capable of hybridizing to a nucleic acid encoding a human RNase III polypeptide, and antisense inhibitors of RNase III expression. Methods of inhibiting RNase III expression or activity are also provided, as are pharmaceutical compositions which include a human RNase III polypeptide, an antisense inhibitor of RNase III expression, or a vector containing a nucleic acid encoding human RNase III. Methods for identifying agents which modulate activity and/or levels of human RNase III are also provided. Methods of promoting inhibition of expression of a selected protein via antisense, methods of screening oligonucleotides to identify active antisense oligonucleotides against a particular target, methods of prognosticating efficacy of antisense therapy, methods of promoting RNA interference (RNAi) or other forms of gene silencing in a cell and methods of eliciting cleavage or modification of a selected cellular RNA target are also provided. All of these methods exploit the RNA-binding and cleaving activity of RNase III polypeptides. In preferred embodiments the polynucleotides used in these methods are RNA-like oligonucleotides. Also provided are methods of identifying agents which increase or decrease activity or levels of human RNase III. The compositions and methods of the present invention are useful for research, biological and clinical purposes. For example, the methods, polynucleotides and antisense oligonucleotides are useful in defining the roles of RNase III and the interaction of human RNase III and cellular RNA (including pre-mRNA or pre-rRNA). Continue reading about Human rnase iii and compositions and uses thereof... Full patent description for Human rnase iii and compositions and uses thereof Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Human rnase iii and compositions and uses thereof patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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