Abstract: A method and a kit for detecting interactions between three or more proteins, in vivo, using reconstitution of the activity of a transcriptional activator is provided. Reconstitution of the transcriptional activator makes use of chimeric genes which express hybrid proteins. In one embodiment, three types of hybrid proteins are prepared. The first hybrid contains the DNA-binding domain of a transcriptional activator fused to the first test protein. The second hybrid protein contains a transcriptional activation domain fused to the second test protein. The third hybrid protein contains a nuclear localization peptide fused to a third test protein and mediates assembly of the three-protein complex involving the three hybrids. If the three test proteins are able to interact, they bring into close proximity the two domains of the transcriptional activator.

Abstract: A novel transcription factor, belong to the E2f gene family, is disclosed. This is called E2F-4. It interacts with DP-1 and can be regulated by p107.

Abstract: Compounds and methods for the treatment of cancer and viral diseases include the administration of viral proteins having substantial homology to BNRF1, FGARAT and/or PRAT. The proteins of the present invention and the nucleic acids encoding such proteins are useful to treat various cancers and uncontrolled cell growth, as well as viral infections, including AIDS. Assays of the present invention are useful in identifying inhibitors of interactions between telomerase, telomeres and viral proteins, especially those that are similar to proteins participating in purine synthesis.

Abstract: A combination of adenoviral and retroviral vectors used to construct second generation packaging cells that deliver marker genes to target cells is described. A vector based upon Moloney murine leukemia virus (MLV) was used to deliver marker genes, and an adenovirus-based delivery system was used to deliver MLV structural genes (gagpol and env) to cultured cells. The procedure transformed the cells into new retroviral producer cells, which generate replication-incompetent retroviral particles in the culture supernatant for transferring marker genes to target cells. The titer of the retroviral-containing supernatant generated from the second generation producer cells reached above 105 cfu/ml which is comparable to the MLV-based producer cell lines currently used in human gene therapy trials. The vector and procedures are adaptable for experimental human gene therapy in which the new producer cells are transplanted into patients for continuous gene transfer.

Abstract: The present invention relates to an expression vector having a foreign DNA. Said DNA at its 3′ end has a sequence which prevents the replication of the expression vector from occurring in the opposite direction to the transcription thereof. The invention also relates to a preparation containing such an expression vector and to the use of both in the permanent expression of foreign DNA in cells.

Abstract: An isolated and purified human Ste20-like serine/threonine signal transduction kinase is described. A cDNA sequence which encodes the native signal transduction molecule is disclosed as well as the structural coding region and the amino acid residue sequence. Methods are provided which employ the sequences to identify compounds that modulate the biological and/or pharmacological activity of the transduction molecule and hence regulate cell physiology. Biologically-effective antisense molecules, as well as dominant negative mutant versions of the biomolecule are described which are suitable for therapeutic use. The invention is also drawn toward the diagnosis, prevention, and treatment of pathophysiological disorders mediated by the signal transduction molecule.

Abstract: This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing T antigen specific cytotoxic T lymphocytes. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are provided to dendritic cells using a viral vector such as influenza virus which may be modified to express non-native antigens for presentation to the dendritic cells. The dendritic cells which are infected with the vector are then capable of presenting the antigen and inducing cytotoxic T lymphocyte activity or may also be used as vaccines.

Abstract: The invention relates to promoters of the genes glutamate dehydrogenase, &bgr;-acetylhexosaminidase and &ggr;-actin and their use in systems of expression, secretion and anti-sense of filamentary fungi. The invention also relates to the use of the promoters of the genes which code: (I) glutamate dehydrogenase NADP depending (EC.1.4.1.4) of Penicillium chrysogenum, (II) &ggr;-N-actylhexosaminidase (EC.3.2.1.52) of Penicillium chrysogenum and (III) &ggr;-actin of Penicillium chrysogenum and Acrimonium chrysogenum, which can be used for the construction of potent vectors of expression and secretion useful both for P. chrysogenum and for A. chrysogenum and related species. These promoters can also be used for blocking the genic expression through anti-sense construction. Under the control of the above mentioned promoters, it is possible to conduct the expression of other genes in filamentary fungi, thereby increasing the production of antibiotics and/or proteins inherent to the same.

Abstract: The present invention is a novel nucleic acid sequence which hybridizes to SEQ ID NO:6 or fragments thereof under stringent conditions, or fragments thereof. The invention also includes diagnostic assays, expression vectors, control sequences, antisense molecule, ribozymes, and host cells to express the polypeptide encoded by the nucleic acid sequence. The present invention also includes claims to the polypeptide sequence coded by the nucleic acid sequences.

Abstract: We have made retrovirus particles displaying a functional antibody fragment. We fused the gene encoding an antibody fragment directed against a hapten with that encoding the viral envelope protein (Pr80env) of the ecotropic Moloney murine leukemia virus. The fusion gene was co-expressed in ecotropic retroviral packaging cells with a retroviral plasmid carrying the neomycin phosphotransferase gene (neo), and retroviral particles with specific hapten biding activities were recovered. Furthermore the hapten-binding particles were able to transfer the neo gene and the antibody-envelope fusion gene to mouse fibroblasts. In principle, the display of antibody fragments on the surface of recombinant retroviral particles could be used to target virus to cells for gene delivery, or to retain the virus in target tissues, or for the construction of libraries of viral display packages.

Abstract: The present invention provides methods of treating hepatitis C infections comprising the step of administering a vector construct which directs the expression of at least one immunogenic portion of a hepatitis C antigen, such that an immune response is generated. Also provided are vector constructs which direct the expression of at least one portion of a hepatitis C antigen, as well as recombinant viruses which carry such vector constructs.

Abstract: Disclosed are novel DNA constructs for selecting plastid transformants in higher plants. Also disclosed are editing based selectable marker genes which require editing at the transcriptional level for expression of the selectable marker gene. Vectors including such edited upstream sequences operably linked to slectable marker genes facilitate the isolation of plastid, rather than nuclear transformants in higher plants.

Abstract: The invention relates to peptide nucleic acids that inhibit telomerase activity in mammalian cells.

Abstract: A spike tissue-specific promoter has been isolated, sequenced and tested. The promoter can be used to make gene constructs including a protein-coding sequence not natively associated with the promoter and a sufficient portion of the promoter such that the portion actuates the preferential expression of the protein-coding sequence in the spike tissue of cereal grain plants.

Abstract: The present invention provides a system for simple generation of recombinant animal viruses. The system includes a virus homing vector and can further comprise a transfer vector. These components are used in a system that reduces the number of cloning steps and provides for easier preparation of a number of recombinant viruses.

Abstract: This invention relates to the use of promoters for ribonucleic acid amplification and other genetic manipulations. Processes are provided wherein complementary deoxyribonucleic acid (cDNA) is synthesized from a ribonucleic acid (RNA) sequence using a complementary primer linked to an RNA polymerase promoter region complement and then anti-sense RNA (aRNA) is transcribed from the cDNA by introducing an RNA polymerase capable of binding to the promoter region. Additional processes using the resulting aRNA are also described.

Abstract: A prokaryotic expression vector including an origin of replication, at least one eukaryotic auxotrophy marker gene which encodes an enzyme required for the synthesis of a product necessary for the survival of at auxotrophic prokaryote under the control of a eukaryotic promoter, a foreign gene under the control of a prokaryotic promoter, and one or more transcription terminators.

Abstract: Disclosed is a process for increasing the yield of disulfide bonded recombinant proteins produced by yeast, especially recombinant secreted proteins The enzyme protein disulfide isomerase (PDI) catalyzes the formation of disulfide bonds in secretory and cell-surface proteins. We disclose the construction of recombinant strains of the yeast Saccharomyces cerevisiae which overproduce either human PDI or yeast PDI in a regulated fashion. These strains show greatly increased secretion of disulfide bonded proteins of potential therapeutic significance. These strains have the potential to increase the production of various disulfide bonded proteins.

Abstract: The present invention demonstrates that BMP-2/4 activates osteopontin gene transcription by removing Hoxc-8 binding through Smad1 interaction with the Hoxc-8 DNA binding domain. Since the DNA binding domain is conserved in all Hox and homeodomain-containing proteins, Smad1 likely interacts with all Hox or homeodomain-containing proteins. Furthermore, the present invention reveals the Smad1-mediated transcriptional mechanism in the BMP-2/4 signaling pathway and also provides information about the transcriptional roles of the Hox genes during embryonic development.

Abstract: The present invention is directed to a process for purifying &agr;1-proteinase inhibitor. The process comprises providing an impure protein fraction which comprises &agr;1-proteinase inhibitor. The impure protein fraction is precipitated with a precipitant comprising PEG. The supernatant from the PEG precipitation, which comprises &agr;1-proteinase inhibitor, is collected and applied to an anion-exchange medium. A fraction comprising &agr;1-proteinase inhibitor is recovered from the anion-exchange medium and applied to a metal chelate medium. A fraction comprising &agr;1-proteinase inhibitor is then recovered from the metal chelate medium. Alpha1-proteinase inhibitor purified by the process has a specific activity greater than 0.6 units/mg.