Abstract: Recombinant pseudoviruses and their use in the production of proteins having medical, agricultural and industrial utilities are discussed.

Abstract: The present invention relates to pseudorabies viruses which fail to produce any functional thymidine kinase as a result of an insertion in the thymidine kinase gene, vaccines against pseudorabies containing the same, and methods for the production and use of the same. The present invention also relates to pseudorabies virus based viral vectors for the coexpression of foreign genes.

Abstract: Infectious bovine rhinotracheitis virus (bovine herpesvirus type 1) mutants containing deletion and/or insertion mutations in a major viral glycoprotein gene, such that no antigenic polypeptides encoded by the viral gene are produced, vaccines for infectious bovine rhinotrachetis containing the same, methods for the production of the same and methods for use of the same. Animals vaccinated with these mutants do not develop antibodies to the viral glycoprotein and can be distinguished serologically from animals infected with infectious bovine rhinotracheitis virus field strains.

Abstract: Novel DNA constructions are provided, as well as their expression products, involving the use of transmembrane integrator sequences joined from one to two open reading frames and optionally a signal sequence, particularly at the N-terminus. The DNA constructs when used with membranal translation systems provide for translocation of the peptides into the membrane. Alternatively, a signal sequence may be introduced internal to an open reading frame, where the resulting translation product may be processed by a membrane to provide two peptides.

Abstract: A novel retinoic acid receptor is disclosed. The novel receptor is encoded for by cDNA carried on plasmid phRAR1, which has been deposited with the American Type Culture Collection for patent purposes. Chimeric receptor proteins are also disclosed. The chimera are constructed by exchanging functional domains between the glucocorticoid, the mineralocorticoid, the estrogen-related, the thyroid and the retinoic acid receptors. In addition, a novel method for identifying functional ligands for receptor proteins is disclosed. The method, which takes advantage of the modular structure of the hormone receptors and the idea that the functional domains may be interchangeable, replaces the DNA-binding domain of a putative novel receptor with the DNA-binding domain of a known receptor such as the glucocorticoid receptor. The resulting chimeric construction, when expressed in cells, produces a hybrid receptor whose activation of a ligand-(e.g.

Abstract: Epithelial cells expressing foreign genetic material are described. The foreign genetic material can be DNA or RNA which does not occur in epithelial cells; DNA or RNA which occurs in epithelial cells but is not expressed in them at levels which are biologically significant; DNA or RNA which occurs in epithelial and has been modified so that it is expressed in epithelial cells; and any DNA or RNA which can be modified to be expressed in epithelial cells, alone or in any combination thereof. In addition, epithelial cells of the present invention can express genetic material encoding a selectable marker by which cells expressing the foreign genetic material can be expressed.

Abstract: A recombinant retrovirus vector is disclosed. It is of the type having a normally replication incompetent retrovirus gene sequence with a foreign eukaryotic gene to be expressed. The retrovirus gene sequence is designed so as to be promoter deficient in the right side LTR. The vector can produce progeny virus from helper cells, which progeny can infect a eukaryotic host cell, form a provirus, and express the eukaryotic gene in the host cell. However, the provirus will then be defective in the retrovirus promoter, such that retrovirus RNA is not expressed from the provirus.

Abstract: A novel cellular enhancer nucleotide sequence causes expression in undifferentiated stem cells of a flanking exogenous or recombinant gene from a promoter accompanying the gene where the gene and promoter are not normally expressed in the undifferentiated stem cells. In the preferred example the essential or basic core of the cellular enhancer nucleotide sequence is ##STR1## The cellular enhancer may encompass a more general core sequence of approximately, for example, in the range of 300 to 350 bases including the essential or basic core sequence. Recombinant vectors including plasmids and viruses are constructed bearing the novel cellular enhancer flanking a recombinant or exogenous gene and promoter having a specified phenotypic trait to be expressed in undifferentiated stem cells. Propagating cells containing the vector constructs reproduce and propagate the vectors.

Abstract: An improved method, employing electroporation, for producing novel recombinant host cells characterized by stably integrated foreign DNA at high copy number. These recombinant host cells are useful in the efficient, large-scale production of recombinant proteins and polypeptides.

Abstract: Recombinant diphtheria toxin A fragment muteins which are enzymatically inactive but immunologically crossreactive with diphtheria toxin are disclosed. Intermediates and methods for preparing such proteins using recombinant techniques are also described.

Abstract: Bacillus brevis strains which produce a large amount of protein but no protease out of the cells are disclosed. These strains are highly useful as hosts in genetic engineering.

Abstract: Disclosed in this patent are DNA sequences, RNA sequences, vectors, and hosts that incorporate a translation enhancer region derived from the 5' non-coding region of a cardiovirus. The enhancer acts at the RNA level (as opposed to the DNA level) to enhance production of proteins in cell free media. Proteinaceous material which is produced will not have attached to it any undesired material from the enhancer sequence. The invention is especially useful to enable efficient production of selected viral proteins of picornoviruses.

Abstract: An animal cell line transformed with an expression vector for an animal cell, the expression vector which contains a DNA segment comprising:(a) a DNA sequence coding for a signal peptide of an animal cell-derived protein,(b) a second DNA sequence coding for a different protein from the signal protein joined downstream of said signal peptide encoding DNA sequence without causing any reading frame shift, and(c) a promoter DNA sequence capable of functioning in an animal cell, wherein the promoter sequence is positioned upstream of the signal peptide encoding DNA sequence, can produce glycosylated proteins advantageously as secretable proteins.

Abstract: This invention is concerned with the specific processing of secreted proteins in genetically modified yeast cells. The yeast KEX1 gene was cloned and the KEX1 product was shown to be a serine protease, evidently a carboxypeptidase B-like protease. A probable site of processing of polypeptides by the KEX1 gene product is at the C-terminus of the .alpha. subunit of the killer toxin, where the mature toxin subunit is followed in the precursor by a pair of basic amino acid residues. Processing likely involves an endoprotease cut following these basic residues, and their subsequent C-terminal trimming by a carboxypeptidase. Consistent with the KEX1 product being this carboxypeptidase is the finding that it is also involved in .alpha.-factor pheromone production. In wildtype yeast, KEX1 is not essential for .alpha.-factor production, as the final hormone repeat in the prepro .alpha.-hormone precursor does not need C-terminal processing to form one copy of the active hormone. However, in a mutant strain where .

Abstract: Exoenzymes, such as proteases, xylanases and amylases, are obtained continuously by cultivation of exoenzyme-producing microorganisms in one step in a fermenter which is operated with continuous flow and in which a deficiency state corresponding to maximal enzyme productivity is effected. Optical density of the culture (as a measure of the biomass density) and exoenzyme concentration in culture can be monitored to control the timing and extent of the deficiency state. It is particularly advantageous to impose an oxygen limitation and to maintain the deficiency state continuously by exerting an effect on the oxygen input.

Abstract: Site-specific mutagenesis of a gene for angiogenin producing DNA sequences encoding mutant proteins having increased angiogenic activity are disclosed. Expression vectors containing these sequences are introduced into host cells and direct the production of the mutant angiogenic proteins with markedly increased angiogenic and ribonucleolytic activity. Replacement of a single amino acid, the aspartic acid at position 116 of human angiogenin, with another amino acid including asparagine, alanine or histidine, yields mutant proteins with 8 to 15 fold increased ribonucleolytic activity toward tRNA and rRNA and 10 to 100 fold increased angiogenic potency in the chorioallantoic membrane assay. The mutant angiogenin proteins of this invention are useful therapeutic compositions to promote the development of a hemovascular network in a mammal or to promote wound healing, in particular, healing of torn or traumatized fibrocartilage material.