Abstract: The present invention relates to plasmids suitable for IL-2 expression, particularly, human IL-2 expression, and related methods.

Abstract: Materials and methods for producing fibrinogen in transgenic non-human mammals are disclosed. DNA segments encoding A.alpha., B.beta. and .gamma. chains of fibrinogen are introduced into the germ line of a non-human mammal, and the mammal or its female progeny produces milk containing fibrinogen expressed from the introduced DNA segments. Non-human mammalian embryos and transgenic non-human mammals carrying DNA segments encoding heterologous fibrinogen polypeptide chains are also disclosed.

Abstract: The present invention provides mouse embryonic stem cells and homozygous mutant mice carrying disruptions in the neurotrophin-3 (NT-3) gene generated by homologous recombination which results in the insertion of a reporter gene or a drug-resistance gene into an exon of the neurotrophin-3 gene. The mice harboring such homozygous mutations have a reduced number of sensory neurons compared with the number of sensory neurons present in a mouse lacking such mutations. These mice may be used to screen for substances that enhance the transcriptional activity of the NT-3 gene.

Abstract: Ice nucleating agents are introduced into or on invertebrates. They elevate the supercooling point of such invertebrates. Where such invertebrates are freeze-intolerant, they may be killed or made susceptible to freezing by subjecting them to temperatures at or below the elevated supercooling point. Food sources treated with ice nucleating agents can be used to introduce the agents effectively to the invertebrate.

Abstract: The present invention discloses novel methods and compositions useful for removing toxic heavy metals from a host organism containing detectable levels of such heavy metals. The method comprises administering to the host organism a therapeutically effective amount of a heavy-metal binding agent which, when saturated with heavy metal atoms, is readily excreted from the body. In a preferred embodiment of the present invention, the binding agent is an oligomeric phosphorothioate oligonucleotide.

Abstract: A newly-characterized chromatin insulator element isolated from the DNA of a higher eukaryotic organism and contained in vector constructs is described. The insulator element of the invention comprises a DNA sequence which contains a 5' constitutive hypersensitive site whose functional activity and biochemical characterization as a pure insulator were previously unknown. A core DNA sequence having strong insulator activity is described. The insulator element, including the core sequence, have been demonstrated for the first time in mammalian cells to function to buffer or insulate an expressed gene from the activity of cis-acting regulatory elements, such as enhancers, in the surrounding chromatin or DNA.

Abstract: A mutant AOX2 (alcohol oxidase 2) promoter derived from the natural AOX2 promoter by base sequence deletion, insertion, or substitution is disclosed. A microbial strain carrying a gene under the control of such a mutant AOX2 promoter can be obtained by growing in a methanol-containing medium a strain incapable of producing AOX encoded by the AOX1 gene but carrying the AOX2 gene under the control of the natural AOX2 promoter. A heterologous protein may be produced by cultivating the mutant strain with the desired heterologous protein gene incorporated downstream from the mutant AOX2 promoter. A plasmid carrying the mutant AOX2 promoter is also provided.

Abstract: Transgenic mice that express increased levels of nerve growth factor (NGF) in the epidermis and other stratified, keratinized epithelium. The nerve growth factor expressing transgenic mice are useful in the study of neurodegenerative disorders of the brain such as Parkinson's syndrome and Alzheimer's disease and for testing for drug candidates for the treatment of these diseases.

Abstract: The present invention relates to a process for integration of a chosen gene or of a specific DNA molecule into the chromosome or episome of a bacterium by cloning the gene or DNA molecule into a defective transposon which is then integrated into the chromosomal or episomal DNA of the bacteria. The defective transposon is incapable of transposition autonomously but can be induced to transpose when properly complemented. The complementation to induce transposition can be limited so that the defective transposon produces a specific number of copies and thereafter is stable. The number of copies of the defective transposon produced during the period of transposition can be estimated by the level of expression of a marker gene contained within the defective transposon.

Abstract: A process for the activation of disulphide linked recombinant proteins expressed in prokaryotes is described. The process includes cell digestion, solubilization under denaturing and reducing conditions and activation under oxidizing conditions in the presence of GSH/GSSG and a non-denaturing amount of a denaturing agent.

Abstract: The present invention relates to a process for transfecting a mammalian cell culture. The process includes incubating a cell culture in the presence of a transfection medium that includes a serum that is of a different type from the serum used in the normal growth medium used to grow the cell culture. It is preferred that the normal growth medium include fetal bovine serum and the transfection medium include a serum such as human, calf, horse, lamb, or pig. The transfection medium may further include an hydryoxylated sterol such as 25-hydroxycholesterol.

Abstract: A novel method for detecting chitin, and for diagnosing fungal infections (including yeast infections), with a chitinase or other chitin-specific binding protein. This method should allow the convenient, broad spectrum diagnosis of fungal infections in tissue samples or in body fluids. Fungal infections are a particular problem in immunocompromised hosts such as AIDS patients, where they can cause opportunistic infections. This invention overcomes difficulties experienced by prior methods of diagnosing fungal infections.

Abstract: Vertebrate gene locus control regions linked to a structural gene of interest and inserted into a transgenic animal are capable of bestowing tissue-independent, copy number-dependent, position-independent gene expression. Recombinant proteins of interest encoded by structural genes linked to the metallothionein locus control regions may be prepared following expression in transgenic animal hosts.

Abstract: Disclosed are methods that achieve i) site-directed delivery, ii) in situ amplification, and iii) sustained expression of an exogenous gene product within renal glomeruli. An exogenous gene, E. coli .beta.-galactosidase, was introduced into cultured rat mesangial cells using a replication-defective retrovirus, and stable infectants were administered to a rat kidney via the renal artery. In the injected kidney, the engineered, cultured mesangial cells populated 40% of glomeruli site-specifically. The gene product was detected throughout a 14-week period of observation. In an alternative method, engineered, cultured mesangial cells were injected into a kidney subjected to an antibody that induces mesangiolysis followed by mesangial regeneration. Under these conditions, expression of .beta.-galactosidase was dramatically amplified in situ, and high level expression continued for at least 8 weeks.

Abstract: The invention relates to a nucleic acid encoding a signal peptide from Bordetella pertussis, a recombinant molecule comprising the signal peptide, and processes for optimizing protein expression in Gram-negative bacteria employing the nucleic acid or signal peptide.

Abstract: This invention provides an isolated, vertebrate nucleic acid molecule encoding the normal protein that prevents development of Wilson's disease. This invention also provides a nucleic acid molecule comprising a nucleic acid molecule of at least 15 nucleotides capable of specifically hybridizing with a sequence included within the sequence of the above-described nucleic acid molecule. Finally, this invention provides various uses of the isolated Wilson's disease gene.

Abstract: A nucleic acid encoding a carcinoembryonic antigen (CEA) that cross-reacts with human CEA is described. In addition, vectors and host cells containing such nucleic acids are disclosed.

Abstract: Prions are protein based infectious material that cause of variety of diseases such as Scrapie, bovine spongiform encephalopathy (also known as "Mad Cow" disease), Creutzfeldt Jakob Disease, Kuru, and fatal familial insomnia. The invention is directed to artificial prion genes that are made up of elements of the prion genes of a host and test species. When these artificial prion genes are inserted into a transgenic mouse, the resultant mouse becomes susceptible to infection with prions that infect the test species but do not normally infect mice. The transgenic animals are useful for testing for the presence of prions in a sample.

Abstract: A method for genetically engineering cells to produce soluble and secretable Golgi processing enzymes instead of naturally occurring membrane-bound enzymes. Cells are genetically engineered to express glycosyltransferases which lack both a membrane anchor and a retention signal. The resulting altered enzyme becomes soluble and secretable by the cell without losing its catalytic activity. Secretion of the soluble glycosyltransferase by the cell provides for increased production and simplified recovery of glycosyltransferase.

Abstract: The present invention relates to long term multiplication and permanent establishment of a cell line of human liver epithelial cells(hepatocytes). The human liver epithelial cell line is capable of mitotically proliferating and continuously growing in vitro under suitable environmental conditions in suitable culture media. A method of producing an immortalized human liver epithelial cell line is also disclosed. The invention also relates to serum-free cell medium developed to support long term multiplication and permanent establishment of a cell line of human liver epithelial cells.