Abstract: The invention provides compositions and methods for signal activated RNA interference (saRNAi), preferably in vivo. The invention provides polynucleotides that switches between an inactive form and an active form upon covalent or non-covalent interaction with one or more specific chemical signals, such as disease-specific mRNA, miRNA, or other cellular RNA products with sequences that characterize diseased states of the cell. The interaction between the subject polynucleotides and the signals is preferably mediated by hybridization, which exposes, facilitates the formation, and/or allows the formation of a substrate that can be processed by proteins of the RNAi pathway (such as Dicer). The input and output of multiple different polynucleotides of the invention can form an in vivo signaling network. In addition, the multiple input signals can be integrated to modulate the activity of the subject polynucleotides.

Abstract: The present invention relates to novel chimeric oligomeric compounds having a plurality of alternating regions having either RNA like having northern or 3?-endo conformational geometry (3?-endo regions) or DNA like having southern or C2?-endo/O4?-endo conformational geometry. The oligomeric compounds of the present invention have shown reduction in mRNA levels in multiple in vitro and in vivo assay systems and are useful, for example, for investigative and therapeutic purposes.

Abstract: The present invention provides compositions comprising cells that can effectively produce HCV after HCV infection, compositions for culturing the cells, methods for making the composition and methods for infecting the cells in the composition with HCV. The present invention also provides methods for assaying HCV production and methods for evaluating compounds that affect the production of HCV.

Abstract: The present invention relates to reagents, methods and systems to treat inflammation and pain in a subject using small interfering RNA (siRNA) molecules targeted to either TNF?, IL1, IL6 and other pro-inflammatory cytokines.

Abstract: The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Abstract: The present invention relates to therapeutic agents useful for the treatment of Severe Acute Respiratory Syndrome (SARS) in humans. In particular, the present invention relates to RNA interference (RNAi) molecules useful for inhibiting the infection and replication of hSARS virus. Preferably, the RNAi molecules target the replicase region of the hSARS virus, or combinations of different sites of hSARS virus genes. The present invention further encompasses methods of using the RNAi molecules for preventing and/or treating SARS. Vaccines and kits comprising therapeutically effective amounts of the RNAi molecules are also encompassed.

Abstract: A pharmaceutical composition and method for inducing or accelerating a healing process of a skin wound are described. The pharmaceutical composition contains, as an active ingredient, a therapeutically effective amount of an agent for either enhancing PKC production and/or enhancing PKC activation; and a pharmaceutically acceptable carrier. The method is effected by administering the composition to a wound.

Abstract: The present invention comprises compositions and methods for delivery systems of agents, including therapeutic compounds, pharmaceutical agents, drugs, detection agents, nucleic acid sequences and biological factors. In general, these vector compositions comprise a colloidal metal, derivatized PEG (polyethylene glycol) and an agent. The invention also comprises methods and compositions for making such colloidal metal compositions and for treatment of cancer.

Abstract: A method of treating a disease resulting from the expression of a harmful gene is described. The method includes the step of administering a therapeutically effective amount of a pharmaceutical composition having at least one double stranded oligonucleotide including two complementary oligonucleotide sequences forming a hybrid. Each oligonucleotide sequence comprises at one of their 3? or 5? ends one to five unpaired nucleotides forming single-strand ends extending beyond the hybrid. One of the oligonucleotide sequences is substantially complementary to a target sequence belonging to a DNA or messenger RNA molecule of a gene coding a mutated or nonmutated androgen receptor.

Abstract: The present invention relates to DNAzymes which are targeted against mRNA molecules encoding EGR-1 (also known as Egr-1 and NGFI-A). The present invention also relates to compositions including these DNAzymes and to methods of treatment involving administration of the DNAzymes.

Abstract: The present invention relates to methods and compositions for inhibiting proliferation and inducing cell death in a population of cancer cells by (i) increasing the amount of the differentiation associated protein MDA-7, and (ii) decreasing RAS activity within the population. It is based, at least in part, on the discovery that decreasing expression of a mutated, activated K-ras gene, together with introducing an expressible mda-7 gene, in pancreatic cells had a synergistic growth-inhibitory and anti-survival effect, and abolished tumorigenicity of the cells in athymic nude mice. The methods of the invention may be directed to the therapy of pancreatic cancer and other malignancies.

Abstract: Compounds, compositions and methods are provided for inhibiting the expression of human STAT3. The compositions comprise antisense oligonucleotides targeted to nucleic acids encoding STAT3. Methods of using these oligonucleotides for inhibition of STAT3 expression and for promotion of apoptosis are provided. Methods for treatment of diseases, particularly inflammatory diseases and cancers, associated with overexpression or constitutive activation of STAT3 or insufficient apoptosis are also provided.

Abstract: This patent application discloses siRNA sequences against the constant region of the ,8 influenza virus nucleoprotein gene comprising: (SEQ ID NO: 1) Sense strand: 5??UGAAGGAUCUUAUUUCUUCdTdT 3? (SEQ ID NO: 2) Anti sense strand: 3??dTdTACUUCCUAGAAUAAAGAAG 5? or (SEQ ID NO: 3) Sense strand: 5??UGAAGGAUCUUAUUUCUUCGGdTdT 3? (SEQ ID NO: 4) Anti sense strand: 3??dTdTACUUCCUAGAAUAAAGAAGCC 5? or (SEQ ID NO: 5) Sense strand: 5??GGAUCUUAUUUCUUCGGAGACdTdT 3? (SEQ ID NO: 6) Anti sense strand: 3??dTdTCCUAGAAUAAAGAAGCCUCUG 5? said sequences being inhibitory against influenza virus in animals including humans. The invention further includes one or more of said siRNA sequences in the form of an aqueous suspension suitable for nasal inhalation. Still further, the invention includes one or more of said siRNA sequences in the form of a plasmid expressing intracellularly in animals including humans.

Abstract: The present invention provides an agent for inhibiting metastasis of colorectal cancer and a method for inhibiting metastasis of colorectal cancer, which inhibit the function of Asef (i.e., binding activity to the APC gene product or guanine nucleotide exchange factor activity) that binds to the gene product of the tumor suppressor gene APC that plays an important role in tumorigenesis and in developmental processes, and/or inhibit the expression of the Asef gene.

Abstract: This patent application discloses siRNA sequences against the constant region of the influenza virus nucleoprotein gene comprising: Sense strand: 5??UGAAGGAUCUUAUUUCUUCdTdT 3? (SEQ ID NO: 1) Anti sense 3??dTdTACUUCCUAGAAUAAAGAAG 5? strand: (SEQ ID NO: 2) or Sense strand: 5??UGAAGGAUCUUAUUUCUUCGGdTdT 3? (SEQ ID NO: 3) Anti sense 3??dTdTACUUCCUAGAAUAAAGAAGCC 5? strand: (SEQ ID NO: 4) or Sense strand: 5??GGAUCUUAUUUCUUCGGAGACdTdT 3? (SEQ ID NO: 5) Anti sense 3??dTdTCCUAGAAUAAAGAAGCCUCUG 5? strand: (SEQ ID NO: 6) said sequences being inhibitory against influenza virus in animals including humans. The invention further includes one or more of said siRNA sequences in the form of an aqueous suspension suitable for nasal inhalation. Still further, the invention includes one or more of said siRNA sequences in the form of a plasmid expressing intracellularly in animals including humans.

Abstract: Treatment of melanoma is achieved through reduction in the effective amount of clusterin in melanoma cells of in a mammalian subject, preferably a human. A therapeutic agent effective to reduce the effective amount of clusterin in the melanoma cells is administered to the subject. The therapeutic agent may be, for example, an antisense ODN or small inhibitory RNA (siRNA) compound targeted to clusterin. bcl-xL in a subject or cell line can also be regulated by administering to the subject or cell line an agent effective to modulate the amount of clusterin expression. In particular, in clusterin expressing cells, the expression of bcl-xL is down-regulated when the effective amount of clusterin is reduced. Such inhibition is significant because bcl-xL is known to act as an inhibitor of apoptosis.

Abstract: The present invention provides a vector system comprising a nucleotide sequence coding for an antibody. In particular, the present invention relates to the use of such a vector system in a subject, where the nucleotide sequence is expressed in vivo to produce said antibody.

Abstract: This invention is directed towards methods of destabilizing proteins in living cells, and their use for the development of novel assays. In one embodiment, the invention comprises the use of non-cleavable multimerized ubiquitin fusion proteins to destabilize a target protein, such as a reporter moiety. In one aspect of this method the constructs also comprises a linker that operatively couples the reporter moiety to the multimerized ubiquitin fusion protein. In this embodiment, enzymatic modification of the linker results in a modulation of the coupling of the reporter protein to the multimerized ubiquitin domains resulting in a change in the stability of the reporter moiety. The level of the reporter moiety in the cell can then be used as a measure of the enzymatic activity in the cell. In another embodiment the invention provides for a generalized way of coordinately regulating the cellular concentration of a plurality of target proteins.

Abstract: Presented are methods and compositions for targeted chromosomal genomic alterations using modified single-stranded oligonucleotides. The oligonucleotides of the invention have at least one modified nuclease-resistant terminal region comprising phosphorothioate linkages, LNA analogs or 2?-O-Me base analogs.

Abstract: Compounds, compositions and methods are provided for modulating the expression of apolipoprotein(a). The compositions comprise oligonucleotides, targeted to nucleic acid encoding apolipoprotein(a). Methods of using these compounds for modulation of apolipoprotein(a) expression and for diagnosis and treatment of disease associated with expression of apolipoprotein(a) are provided.