Abstract: Embodiments of the inventions relates to modulating NFAT activity, modulating store-operated Ca2+ entry into a cell and treating and/or preventing hyperactivity or inappropriate immune response by inhibiting the expression or activities of proteins involved in the calcineurin/NFAT axis.

Abstract: The present invention provides for novel methods for regulating and detecting the cytosine methylation status of DNA. The invention is based upon identification of a novel and surprising catalytic activity for the family of TET proteins, namely TET1, TET2, TET3, and CXXC4. The novel activity is related to the enzymes being capable of converting the cytosine nucleotide 5-methylcytosine into 5-hydroxymethylcytosine by hydroxylation.

Abstract: The present invention provides an isolated polypeptide capable of binding to aCAM-1, comprising the integrin (XL I domain or biologically active portion thereof, wherein one or more residues is substituted, wherein the substituted polypeptide binds ICAM-I at a higher affinity than wild type integrin CCL protein. The invention provides a method for inhibiting ICAM-I and a pharmaceutical composition comprising an integrin (XL I domain polypeptide or biologically active portion of the polypeptides. The invention also provides a method of treating or preventing an LFA-I mediated ICAM-1 associated disease such as inflammation, artherosclerosis, allograft rejection, diabetes, T-cell mediated sensitization reaction, psoriasis, HIV infection, or rheumatoid arthritis.

Abstract: The present invention generally relates to methods and compositions for the simultaneous delivery of at least one insoluble agent and at least one soluble agent to a cell. In particular the present invention relates to methods and compositions for the dual delivery of an insoluble agent and a soluble agent to a particular target cell, for example, a leukocyte or endothelial cell. In particular, methods and compositions for simultaneous delivery of a hydrophilic (i.e. soluble) agent and/or a hydrophobic (i.e. insoluble) agent to a leukocyte cell or endothelia cell are disclosed.

Abstract: Described herein are methods and compositions for the inhibition of retroviral integration and replication. The methods and compositions inhibit the activity of one or more components of the SET complex or base excision repair enzymes and induce autointegration of retroviral double-stranded nucleic acid.

Abstract: The invention provides a microbicidal composition comprising at least one siRNA. The siRNA is an RNA duplex made of one or two molecules. A portion of the siRNA is identical to a target sequence in an essential gene of a virus. The virus may be a herpesvirus, for example, HSV-1 or HSV-2. Preferably, the herpesvirus is HSV-2. The microbicidal composition further comprises a pharmaceutically acceptable carrier. Also included in the invention are methods to prevent and treat viral infections by administration of the microbicidal composition. Preferably, the microbicidal composition is administered transmucosally.

Abstract: This invention relates to knockout mice for the Ca2+ sensor membrane protein STIM-1, STIM-2, or both, as well as cell lines from these knockout mice. Provided herein are various methods of use of isolated with knockout STIM-1 and/or STIM-2.

Abstract: In one aspect, the invention relates to the treatment and/or prevention of inflammation by inhibition of cyclin D1. In one embodiment, Th1-mediated inflammation is selectively inhibited or reduced by a method comprising administering an agent that inhibits cyclin D1. In another embodiment, an autoimmune disease or a disorder characterized by or involving a Th1 inflammatory response is treated or prevented in a subject by a method comprising administering to the subject an agent that inhibits cyclin D1.

Abstract: Disclosed herein are methods for treating and/or preventing HIV infection in a cell. The methods involve downmodulating one or more of the HIV-dependency factors (HDFs) disclosed herein to thereby treat and/or prevent HIV infection in the cell. Downmodulating the HDFs can be by contacting the cell with an agent that downmodulates the HDF. Also disclosed herein are methods for treating and/or preventing HIV infection in a subject comprising downmodulating one or more of the HIV-dependency factors (HDFs), disclosed herein, to thereby treat and/or prevent HIV infection in the subject. The method may further comprise selecting a subject diagnosed with or at risk for HIV infection, prior to downmodulating. Downmodulating the HDFs may comprise administering an agent that downmodulates the HDF to the subject such that the agent contacts HIV host cells of the subject. The agent may inhibit HDF gene expression, protein synthesis, HDF function or HDF activity, or combinations thereof.

Abstract: Isolated peptide fragments of the conserved regulatory domain of NFAT protein capable of inhibiting protein-protein interaction between calcineurin and NFAT, or a biologically active analog thereof are described. Isolated polynucleotides and gene therapy vectors encoding such peptide fragments are also described. In addition, methods for treating immune-related diseases or conditions and methods for high throughput screening of candidate agents are described. Pharmaceutical compositions are also provided.

Abstract: The present invention provides compositions and methods useful for delivering agents to target cells or tissues, for example nerve cells and other cells in the central nervous system. The compositions and methods are useful for delivering agents across the blood-brain barrier. The present invention also provides methods of using the compositions provided by the present invention to deliver agents, for example therapeutic agents for the treatment of neurologically related disorders.

Abstract: The present invention provides a method of delivering RNA interference molecules to a cell or a cell in a subject, which comprises contacting the cell with a protein-double stranded RNA complex, the complex comprising the double stranded RNA segment containing a double stranded RNA of interest and a protein, the protein comprising (1) a targeting moiety, which will specifically bind to a site on a target cell, and (2) a binding moiety linked thereto, which will bind to the double stranded RNA, wherein the double stranded RNA segment is delivered to a cell and effects RNA interference of the target RNA in the cell.

Abstract: The methods and compositions described herein are based, in part, on the discovery that the introduction of a disulfide bond into an integrin polypeptide by the substitution of at least one cysteine residue in the polypeptide permits stabilization of the integrin in a “closed/inactive” state. This stabilizing disulfide bond permits integrins to be screened for a candidate molecule that can bind to the closed state. In particular, this approach can be used to screen for agents that bind to the closed state of an integrin polypeptide, and are useful as therapeutic treatments to prevent integrin activation.

Abstract: The present invention is based, at least in part, on the discovery of compositions and methods for the treatment and prevention of infectious diseases or disorders, e.g., HIV infection, AIDS, and AIDS-related diseases. In particular, the present invention pertains to methods of modulating cellular gene expression or protein activity, e.g., CCR5, gene expression or protein activity and/or gene expression or protein activity of a gene or sequence of an infectious agent, in order to treat or prevent infectious diseases or disorders, HIV infection, AIDS, or an AIDS-related disease or disorder. In one embodiment the combination of an RNA interfering agent targeting a cellular gene in combination with an RNA interfering agent targeting a gene or sequence of an infectious agent results in prolonged prevention of infection by an infectious agent. The present invention is based on the identification of novel RNA interference agents, e.g., siRNA molecules, which target cellular genes, e.g., chemokine receptors, e.g.

Abstract: Disclosed are delivery agents for selective delivery to leukocytes. The leukocyte-selective delivery agents comprise a targeting moiety that selectively binds LFA-I, a non-protein carrier moiety covalently linked to the targeting moiety and a therapeutic agent associated with the carrier moiety. The non-protein carrier moiety comprises a liposome, a micelle, or a polymeric nanoparticle comprised of PLA or PLGA. The delivery agent may be further selective for activated leukocytes by using a targeting moiety that selectively binds LFA-I in its activated conformation. The targeting moiety may comprise an antibody or functional fragment thereof such as an scFV. Appropriate therapeutic agents include a nucleic acid, a small molecule, a polypeptide, and an antibody or functional fragment thereof. Additional examples of therapeutic agents are a small RNA, an antagomir, an LNA, or an antisense oligonucleotide. One such therapeutic agent is an RNA interference molecule such as siRNA, dsRNA, stRNA, shRNA, miRNA.

Abstract: This invention relates to methods for treating or preventing an infarction by administering to a patient in need thereof a compound capable of suppressing the expression or activity of the von Willebrand Factor (VWF). Thus, the invention relates to the use of a pharmaceutically effective amount of a VWF inhibitor, such as ADAMTS13, for the preparation of a medicament for treating conditions known to involve infarction to reduce or eliminate the symptoms and effect of an infarction.

Abstract: The invention provides a method for a multi-layered lipid particles in the form of liposomes that are coated first with a cryoprotectant followed by a targeting moiety over the coat of cryoprotectant, and a method for encapsulating drugs and agents in the multi-layered coated liposomes. In addition, ready-to-use liposome kits for coating with targeting agent of choice and for drug and/or agent encapsulation.

Abstract: The present invention relates, in part, to the C. elegans SKN-1 gene and protein (a transcription factor), and target genes thereof. The invention includes various therapeutic methods and screening methods for identifying antioxidants.

Abstract: Disclosed are methods of identifying an agent that modulates an NFAT regulator protein. One such method comprises contacting at least one test agent with a recombinant cell comprising at least one NFAT regulator protein or fragment or derivative thereof, assessing the effect of the test agent on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, and identifying the test agent that has an effect on an activity, interaction, expression, or binding to the NFAT regulator protein or fragment or derivative thereof, whereby the identified test agent is characterized as an agent that modulates an NFAT regulator protein.

Abstract: The present invention is directed to methods of treating flavivirus mediated diseases using siRNAs. The invention is based upon our findings in a mouse model that siRNAs directed against sequences conserved among multiple flaviviruses prevents and treats flavivirus infections. Accordingly, the present invention provides an isolated siRNA comprising a sense RNA and an antisense RNA strand or a single strand. The sense and the antisense RNA strands, or the single RNA strand, form an RNA duplex, and wherein the RNA strand comprises a nucleotide sequence identical to a target sequence of about 15 to about 30 contiguous nucleotides in flavivirus mRNA or mutant or variant thereof.