Abstract: The invention is directed to the induction of mitochondrial membrane permeabilization via the physical and functional interaction of the HIV-1 Vpr protein with the mitochondrial inner membrane protein ANT (adenine nucleotide translocator, also called adenine nucleotide translocase or ADP/ATP carrier). Reagents and methods for inducing and/or inhibiting the binding of Vpr to ANT, mitochondrial membrane permeabilization, and apoptosis are provided.

Abstract: An invention comprising cellular transformation, directed evolution, and screening methods for creating novel transgenic organisms having desirable properties. Thus in one aspect, this invention relates to a method of generating a transgenic organism, such as a microbe or a plant, having a plurality of traits that are differentially activatable. Also, a method of retooling genes and gene pathways by the introduction of regulatory sequences, such as promoters, that are operable in an intended host, thus conferring operability to a novel gene pathway when it is introduced into an intended host. For example a novel man-made gene pathway, generated based on microbially-derived progenitor templates, that is operable in a plant cell. Furthermore, a method of generating novel host organisms having increased expression of desirable traits, recombinant genes, and gene products.

Abstract: A method of immunization, and compositions therefor, are provided for substantially preventing or reducing the symptoms of at least one infectious disease and at least one chronic immune mediated disorder. An immunogenic challenge which supplements the normal childhood immunization schedule can help ensure the proper maturation of the immune system and prevent the development of chronic immune mediated disorders, such as immune-mediated diabetes or SLE.

Abstract: Recombinant PB2 tryptophan variant influenza viruses, RNA, cDNA and vectors are provided. Also provided are immunogenic compositions containing the variant viruses, methods of producing such viruses and methods for the prophylactic treatment of influenza in humans.

Abstract: A method for producing viral vectors is described using packaging and producer cell lines is described. The producer cell comprises: (i) a first nucleotide sequence (NS) encoding a toxic viral envelope protein operably linked to a promoter; wherein the promoter is operably linked to at least one copy of a TRE; (ii) a second NS wherein the second NS comprises a sequence encoding a tetracycline modulator; (iii) a third NS encoding a retrovirus nucleocapsid protein; and (iv) a fourth NS comprising a retroviral sequence capable of being encapsidated in the nucleocapsid protein such that the retroviral vector particle titre obtainable from the producer cell is regulatable by tetracycline and an initial stimulus with sodium butyrate or functional analogues thereof.

Abstract: A chimeric skin comprising immortalized human keratinocyte cells cocultured with donor keratinocytes is disclosed.

Abstract: Methods for inhibiting viral propagation and treating viral infection are provided which include administering to cells infected with viruses a therapeutic peptide or a derivative thereof.

Abstract: The present invention provides methods of identifying anti-HIV compound by contacting human Vpr Interacting Protein (hVIP), or a fragment thereof known to interact with Vpr, with Vpr, or a fragment thereof known to interact with hVIP in the presence of a test compound, and comparing the affinity of the hVIP or fragment thereof to the Vpr or fragment thereof in the presence of the test compound with the affinity of the hVIP or fragment thereof to the Vpr or fragment thereof in the absence of the test compound. The present invention also provides transgenic non-human mammals comprising a recombinant expression vector that comprises a nucleic acid sequence that encodes hVIP.

Abstract: This invention provides methods of obtaining novel polynucleotides and encoded polypeptides by the use of non-stochastic methods of directed evolution (DirectEvolution™). A particular advantage of exonuclease-mediated reassembly methods is the ability to reassemble nucleic acid strands that would otherwise be problematic to chimerize. Exonuclease-mediated reassembly methods can be used in combination with other mutagenesis methods provided herein. These methods include non-stochastic polynucleotide site-saturation mutagenesis (Gene Site Saturation Mutagenesis™) and non-stochastic polynucleotide reassembly (GeneReassembly™). This invention provides methods of obtaining novel enzymes that have optimized physical &/or biological properties. Through use of the claimed methods, genetic vaccines, enzymes, small molecules, and other desirable molecules can be evolved towards desirable properties. For example, vaccine vectors can be obtained that exhibit increased efficacy for use as genetic vaccines.

Abstract: The present invention relates to methods of screening for target polypeptides that bind to RNA, using affinity purification methods, and the use of such target polypeptide for drug discovery and in methods of treating and preventing disease, e.g., HCV infection.

Abstract: The present invention features an isolated, intact virus associated with human lymphoma, and originally isolated from a mantle cell lymphoma, referred to herein as a mantle histiocyte retrovirus (MHRV). The invention also features compositions and methods for detecting MHRV, as well as methods and compositions for propagating MHRV in vitro, screening for anti-MHRV agents, and generation of attenuated MHRV strains.

Abstract: This invention provides a compound comprising the structure: ??YDINYYTSE?? wherein each T represents a threonine, each S represents a serine, each E represents a glutamic acid, each Y represents a tyrosine; each D represents an aspartic acid, each I represents an isoleucine; and each N represents an asparagine; wherein ? represents from 0 to 9 amino acids, with the proviso that if there are more than 2 amino acids, they are joined by peptide bonds in consecutive order and have a sequence identical to the sequence set forth in SEQ ID NO: 1 beginning with the I at position 9 and extending therefrom in the amino terminal direction; wherein ? represents from 0 to 13 amino acids, with the proviso that if there are more than 2 amino acids, they are joined by peptide bonds in consecutive order and have a sequence identical to the sequence set forth in SEQ ID NO: 1 beginning with the P at position 19 and extending therefrom in the carboxy terminal direction; wherein ? represents an amino group or an acetylated amino

Abstract: This document describes compositions and methods for inducing an immune response (e.g., a cellular response such as a cell-mediated cytolytic immune response) to a human papillomavirus (HPV) antigen, which can be displayed by HPV or exhibited by infected cells (e.g., cells from cervical and other tumors). The HPV protein can be joined to a stress protein by chemical conjugation or noncovalently using linking moieties, or by fusion (e.g., a recombinant fusion protein). Also described are expression vectors containing sequences encoding HPV antigens and stress proteins, which can be introduced into cells of a subject or cells ex vivo. Also described are compositions that include a stress protein linked to an HPV antigen and another pharmacologically acceptable component and stress protein—HPV antigen fusions and conjugates. These compositions can be used to induce or enhance an immune response against HPV and cells that exhibit HPV antigens, including HPV-associated tumors.

Abstract: Disclosed is a method for treating infection with a pathogen. The method involves administration of: (1) a substance which induces active pathogen replication in a cell latently infected with HIV and (2) an anti-pathogen drug. Also disclosed are methods for expanding CD4+ T cells from peripheral blood mononuclear cells isolated from human subjects in the presence of an antiretroviral drug and for treating HIV infection by infusing the expanded CD4+ cells into HIV-infected patients.

Abstract: The present invention provides a highly dispersible formulation comprising an active agent and a dipeptide or tripeptide comprising at least two leucyl residues. The composition of the invention possesses superior aerosol properties and is thus preferred for aerosolized administration to the lung. Also provided are a method for (i) increasing the dispersibility of an active-agent containing formulation for administration to the lung, and (ii) delivery of the composition to the lungs of a subject.

Abstract: Compositions and methods for making and using therapeutic formulations of antimicrobial cationic peptides are provided. The antimicrobial cationic peptide formulations may be used, for example, in the treatment of microorganism-caused infections, which infections may be systemic, such as a septicemia, or may be localized, such as in acne or an implanted or indwelling medical device.

Abstract: A method to identify internal ribosome entry site (IRES) elements using a bicistronic expression system for reporter proteins is described. The IRES elements thus identified are useful in identifying trans-acting translation factors and as antiviral agents.

Abstract: The invention provides antisense antiviral compounds and methods of their use in inhibition of growth of viruses of the picornavirus, calicivirus, togavirus and flavivirus families, as in treatment of a viral infection. The antisense antiviral compounds are substantially uncharged oligomers having a targeting base sequence that is substantially complementary to a viral target sequence which spans the AUG start site of the first open reading frame of the viral genome.

Abstract: This invention relates to methods of using human dendritic cells to present antigens for the induction of antigen-specific T cell-mediated immune responses. In particular, it relates to the isolation of dendritic cells from human blood, exposing the cells to antigens, co-culturing the antigen-pulsed dendritic cells with &ggr;&dgr;-T cell receptor-positive-T cells (&ggr;&dgr;-TCR+ T cells) obtained from unprimed or weakly primed individuals for the stimulation of antigen-specific T cell proliferative and cytotoxic activities. The dendritic cell antigen presentation system described herein has a wide range of applications, including but not limited to, activation and expansion of large numbers of antigen-specific major histocompatibility complex-unrestricted T cells for use in adoptive cellular immunotherapy against infectious diseases and cancer.

Abstract: A method for quantifying an HIV protease inhibitor in a sample includes combining HIV protease, a conjugate comprising an HIV protease inhibitor analog, and a sample suspected of containing an HIV protease inhibitor. The HIV protease and the conjugate are capable of forming a detectable complex. The method also includes measuring the amount of the detectable complex, and relating the amount of the detectable complex to a concentration of the HIV protease inhibitor in the sample.