Abstract: A host-vector system suitable for production of human growth hormone (hGH) and a process for production of hGH using the same are provided. As an hGH expression plasmid, a recombinant DNA wherein a DNA coding for hGH is linked to the 3'-terminal of a DNA containing a promoter region derived from Bacillus brevis is provided, and as a host, especially a mutant Bacillus brevis substantially not exhibiting protease activity to hGH is provided. A microorganism obtained by transforming said host with said hGH expression plasmid efficiently produces hGH when it is cultured.

Abstract: The present invention is directed to expression cassettes comprising a 5' regulatory region from at least one of the Pichia pastoris AOXI gene, p40 gene, DASI gene or HIS4 gene, operably linked to an HSA structural gene including the HSA signal sequence. The HSA structural gene has a translational start codon within 0 to 11 deoxyribonucleotides from the 5' end of the HSA structural gene and is operably linked to a 3' termination sequence. Further, the adenine and thymine content of the intervening deoxyribonucleotides is in the range from about 55 to about 64%. The expression cassette may be an autonomously replicating vector or an integrative vector. Other embodiments of the present invention include Pichia pastoris strains transformed with the HSA expression cassettes and processes for secretion of HSA using the expression cassettes.

Abstract: Production of proteins in bacteria containing DNA sequences encoding proteins under the control of a temperature-regulated promotor is improved by growing the organisms at temperatures of less than 35.degree. C. until the late logarithmic phase. Thereafter the temperature may be raised to 36.degree. C. to 39.degree. C. Antigens produced by the method of the invention may be used as vaccines, as means for measuring efficacy of vaccines, as probes to detect antigens from clinical samples and for biochemical characterization of antigens.

Abstract: A pharmaceutical preparation containing a complex consisting of type B botulinum neurotoxin and stabilizing proteins, both derived from C. botulinum, admixed with a pharmaceutically acceptable excipient is provided. The preparation is effective for inducing titratable, local, selective muscle denervation in a patient suffering from a disorder characterized by involuntary muscle spasm or contraction.

Abstract: A novel expression system is provided comprising a DNA sequence containing transcriptional and translational signals that promote the over production of recombinant proteins both in bacterial hosts (e.g., Escherichia coli) and yeasts (e.g., Saccharomyces cerevisiae). The design of the expression system lends itself to a unique strategy which allows heterologous genes to be directly cloned at a position relative to the transcription/translation signals which is optimal for expression. Particularly provided are expression cassettes comprising a sequence of the invention combined with a purpose built series of plasmids wherein the utility and efficiency of the resultant expression vectors can be demonstrated to over produce protein, particularly phenylalanine ammonia lyase (herein abbreviated to PAL), in E. coli and S. cerevisiae to levels hitherto unattainable.

Abstract: The present invention provides an efficient, cost effective method for transforming, including stably transforming, plants including monocots, dicots and gymnosperms. The method of the present invention, which is less labor intensive than typical conventional transformation methods, comprises combining the plant and a vector which contains the foreign nucleic acid to be introduced into the plant sample. Preferably the plant sample is sonicated in the presence of the vector. The vector is preferably non-tumor inducing bacteria, more preferably Agrobacterium. The sonication duration is less than 15 minutes, preferably less than 6 minutes more preferably 60 seconds or less. After sonicating the plant sample is cultured under conditions that induce morphogenesis to produce plant tissue that will mature into a transformed plant.

Abstract: A recombinant DNA vector is provided that expresses exons of genomic DNA fragments that are inserted into the vector. The vector contains a promoter and a genomic DNA fragment so characterized and configured that the vector, upon transcription in a transfected eukaryotic cell culture, expresses the corresponding RNA segment of the genomic DNA fragment free of any intron.

Abstract: This invention relates to a method of quantifying bacteria in vivo or in vitro using bacterial reporter strains. In particular this invention provides a method utilizing mycobacterial reporter strains that permits rapid screening for in vivo antimycobacterial activity of various compositions. In addition this invention provides for particular mycobacterial reporter strains expressing the FFlux gene at levels sufficiently high to allow detection in tissue homogenates without lysis or concentration of the bacteria.

Abstract: The invention includes novel fusion DNA sequences encoding fusion polypeptides which when expressed in a filamentous fungus result in increased levels of secretion of the desired polypeptide as compared to the expression and secretion of such polypeptides from filamentous fungi transformed with previously used DNA sequences. The fusion DNA sequences comprise from the 5' terminus four DNA sequences which encode a fusion polypeptide comprising, from the amino to carbonyl-terminus, first, second, third and fourth amino acid sequences. The first DNA sequence encodes a signal peptide functional as a secretory sequence in a first filamentous fungus. The second DNA sequence encodes a secreted polypeptide or portion thereof which is normally secreted from the same filamentous fungus or a second filamentous fungus. The third DNA sequence encodes a cleavable linker polypeptide while the fourth DNA sequence encodes a desired polypeptide.

Abstract: The invention relates to the discovery of a gene, NMD2, named after its role in the Nonsense-Mediated mRNA Decay pathway, and the protein, Nmd2p, encoded by the NMD2 gene. The amino acid sequence of Nmd2p and the nucleotide sequence of the NMD2 gene encoding it are disclosed. Nmd2p is shown herein to bind to another protein in the decay pathway, Upf1p. A C-terminal fragment of the protein is also shown to bind Upf1p and, when overexpressed in the host cell, the fragment inhibits the function of Upf1p, thereby inhibiting the nonsense-mediated mRNA decay pathway. The invention also relates to methods of inhibiting the nonsense-mediated mRNA decay pathway to stabilize mRNA transcripts containing a nonsense codon which normally would cause an increase in the transcript decay rate. Such stabilization of a transcript is useful for the production of a recombinant protein or fragment thereof.

Abstract: The present invention relates to methods and compositions for the diagnosis, prevention, and treatment of tumor progression in cells involved in human tumors such as melanomas, breast, gastrointestinal, lung, and bone tumors, various types of skin cancers, and other neoplastic conditions such as leukemias and lymphomas. Genes are identified that are differentially expressed in benign (e.g., non-malignant) tumor cells relative to malignant tumor cells exhibiting a high metastatic potential. Genes are also identified via the ability of their gene products to interact with gene products involved in the progression to, and/or aggressiveness of, neoplastic tumor disease states. The genes and gene products identified can be used diagnostically or for therapeutic intervention.

Abstract: Endothelial cells transduced with genetic material encoding a polypeptide or protein of interest and, optionally, a selectable marker, as well as methods for making and using the transduced endothelial cells are disclosed. Such endothelial cells are useful in improving the performance of vascular grafts and in delivering the encoded polypeptide or protein, such as an enzyme, a hormone, a receptor or a drug, to an individual.

Abstract: A method of inhibiting the growth of a virus, the DNA of the virus including the nucleic acid sequence 5' ACCXNNNPyCGGTXY3', wherein each N, X, and Y is, independently, any nucleotide, and Py is C or T, the nucleic acid sequence being capable of binding to a protein encoded by the DNA of the virus, the protein, upon binding to the nucleic acid sequence, being capable of causing the enhancement of the transcription of DNA of the virus, the method including inhibiting the protein from binding to the nucleic acid sequence to repress the transcription of DNA of said virus to inhibit the growth of the virus.

Abstract: A methodology that allows for highly efficient transfer and stable integration of DNA into both established eukaryotic cell lines and primary cells, including non-dividing cells such as human peripheral blood monocytes and macrophages, entails the use of a synthetic polypeptide comprised of a peptide domain which corresponds to a nuclear localization signal sequence and a DNA binding domain which is rich in basic amino acids, separated by a hinge region of neutral amino acid which prevents stearic interference between the two domains.

Abstract: The invention features an isolated herpesvirus glucocorticoid response element comprising a DNA sequence comprising two consensus hexanucleotide glucocorticoid receptor binding sequences having at least five nucleotides positioned therebetween. The invention further features compositions and methods for preventing herpesvirus replication and reactivation.

Abstract: A self-assembling polynucleotide delivery system comprises a dendrimer polycation aiding in the delivery of the polynucleotide to a desired address, and optionally other agents such as DNA masking agents, cell recognition agents, charge-neutralization agents, membrane-permeabilization agents, and subcellular-localization agents.

Abstract: The present invention offers the serine protease exhibiting a biological activity which a polypeptide having an amino acid sequence shown in FIG. 1 shows, the serine protease precursor where a cleavable peptide or signal peptide connects with the N-terminal of the said serine protease, and the gene encoding them. The serine protease being useful in medical treatment fields can be manufactured in large quantities by the present invention.Moreover, the present invention offers the DNA sequence coding a transcription controlling region contained in the chromosomal gene of the serine protease of a human myeloid cell. This sequence is the transcription controlling region being necessary for the gene expression being specific to a human leukocyte or erythrocyte.

Abstract: The present invention provides regulatory elements that are linked to genes involved in cell death. For example, the present invention provides a p53-RE.sup.D, which is involved in p53-mediated down-regulation of the bcl-2 gene, and the bax promotor, which contains a p53-RE.sup.U that is involved in p53-mediated up-regulation of the bax gene. The invention also provides screening assays for identifying agents such as drugs that effectively modulate expression of a gene that is involved in cell death. In addition, the invention provides methods for modulating the level of apoptosis in a cell.

Abstract: The present invention provides a dual method for producing male-sterile plants. Two genetically transformed plants, parents 1 and 2 are crossed to obtain male-sterile offspring. Parent 1 is transformed with an expression cassette comprising a nucleotide sequence encoding an anther-specific promoter which is operably linked to a nucleotide sequence encoding a transactivator. Parent 2 is transformed with an expression cassette comprising a target nucleotide sequence, which is capable of being activated by the transactivator, operably linked to a nucleotide sequence which encodes RNA or a polypeptide which will disrupt the formation of viable pollen. Therefore, crossing parent 1 with parent 2 results in male-sterile offspring. The male-sterile plants are useful for producing hybrid seed.The invention also provides compositions and methods for high level expression of a coding region of interest in a plant.

Abstract: The invention concerns a process for the production of recombinant proteins in streptomycetes in which the expression is carried out in Streptomyces galbus DSM 40480, preferably under the control of the ermE-up promoter or an inducible promoter.