Abstract: Methods for treating respiratory disease, including cystic fibrosis, emphysema, bronchitis, and sinusitis are presented. Methods comprise administering to a patient an effective amount of DNA in a manner so as not to effect gene transfer and expression.

Abstract: The present invention provides methods of producing a canine animal model of cancer. The method comprising introducing a heterologous tumor cell into an pre-mature, preimmunocompetent canine animal under conditions that induce immune tolerance to the tumor cell. The tumor cell is then allowed to proliferate in the canine animal, thereby forming a tumor.

Abstract: The present invention provides a mammalian artificial chromosome (MAC), comprising a centromere and a unique cloning site, said MAC containing less than 0.1% of the DNA present in a normal haploid genome of the mammalian cell from which the centromere was obtained. The invention further provides a MAC, wherein the unique cloning site is a nucleic acid sequence encoding a selectable marker. The invention also provides methods of preparing a MAC. In addition, the invention provides methods of stably expressing a selectable marker in a cell, comprising introducing a MAC containing the selectable marker into the cell. The invention also provides a cell containing a MAC expressing an exogenous nucleic acid sequence and a transgenic mammal expressing a selectable marker.

Abstract: Recombinant methods for recovering wildtype or engineered negative stranded, non-segmented RNA virus genomes containing non-coding 3' and 5' regions (e.g. leader or trailer regions) surrounding one, several or all of the genes of the virus or one or more heterologous gene(s) in the form of ribonucleocapsids containing N, P and L proteins, which are capable of replicating and assembling with the remaining structural proteins to bud and form virions, or which are only capable of infecting one cell, or are defective interfering particles, are disclosed. Novel vaccines, gene therapy vectors and antiviral compounds are also disclosed.

Abstract: The present invention relates to expression of recombinant proteins by use of a bacterial host expression vector which expresses a recombinant protein under the control of a first regulatory expression element, and expresses a selectable marker under the control of a second regulatory expression element, which second element is mutated such that expression of the selectable marker is at reduced levels relative to that directed by such an unmutated expression element. Such an expression vector in a suitable bacterial host (a) allows ease of purification of the recombinant protein of interest ("the recombinant protein") since less selectable marker is present to interfere with the purification of the recombinant protein, and (b) increases the amount of recombinant protein that is produced by the bacterial host cell.

Abstract: Disclosed is a mouse in which expression of the gene encoding the CTLA-4 receptor is suppressed. Also disclosed is a nucleic acid construct useful in preparing such a mouse, and a cell line containing such construct.

Abstract: The invention concerns a new method for the simultaneous sequencing of nucleic acids using numerous double-stranded DNA adaptors.

Abstract: Transgenic animals capable of expressing a desired protein can be prepared by co-introducing into an egg or embryo cell of an animal, a first sequence, which encodes the desired protein, and a second, more efficiently expressed, DNA sequence. Expression efficiency is thereby conferred on the first sequence, leading to improved yield or targeting, or both. Co-introduction may be achieved by co-injecting a mixture of the two DNA sequences into a fertilized egg, in the case of an animal. The invention can be used to enhance the efficiency of expression of desired proteins, such as those having pharmaceutical activity in the mammary gland of a female transgenic animal.

Abstract: Mammalian cells which express apoaequorin and a receptor involved in the modulation of intracellular calcium are provided by the present invention. Transgenic mice in which neuronal cells express aequorin are also provided. Methods of use are provided.

Abstract: The present invention comprises compositions and preparations for the promotion of wound healing in an animal. Methods for preparing the compositions as well as methods for using the compositions to achieve the promotion of wound healing are also provided. Methods for enhancing collagen production at a wound site are also disclosed. The composition may comprise a dietary regimen or a therapeutic agent. These compositions include a wound healing promoting concentration of ribonucleotides in a pharmaceutically acceptable carrier solution. By way of example, such ribonucleotides may comprise RNA, adenine, uracil or a mixture thereof. The compositions can be prepared as suitable for oral, parenteral, intravenous or topical administration. Methods for using the preparation as a treatment to enhance the healing of an already existing wound or for use as a pretreatment regimen for animals in anticipation of surgery, are also disclosed.

Abstract: The present invention relates to novel methods for sequencing and mapping genetic markers in polynucleotide sequences using Type-IIs restriction endonucleases. The methods herein described result in the "capturing" and determination of specific oligonucleotide sequences located adjacent to Type-IIs restriction sites. The resulting sequences are useful as effective markers for use in genetic mapping, screening and manipulation.

Abstract: The invention provides methods and compositions relating to a novel tumor necrosis factor receptor associated factor number six (TRAF6) protein, which transcriptionally activates Nuclear Factor .kappa.B. The invention provides isolated TRAF6 hybridization probes and primers capable of hybridizing with the disclosed TRAF6 gene, nucleic acids encoding the subject TRAF6 proteins, methods of making the subject TRAF6 proteins, and methods of using the subject compositions in diagnosis and drug screening.

Abstract: A method for the direct treatment towards the specific sites of a disease is disclosed. This method is based on the delivery of proteins by catheterization to discrete blood vessel segments using genetically modified or normal cells or other vector systems. Endothelial cells expressing recombinant therapeutic agent or diagnostic proteins are situated on the walls of the blood vessel or in the tissue perfused by the vessel in a patient. This technique, provides for the transfer of cells or vectors and expression of recombinant genes in vivo and allows the introduction of proteins of therapeutic or diagnostic value for the treatment of diseases.

Abstract: The present invention provides oligonucleotide sequences comprising DNA regulatory elements comprising point mutations of Ly6E GAS element that bind activated transcriptional regulatory proteins in response to signaling molecules, such as cytokines. Further, the present invention also provides DNA constructs comprising the oligonucleotide sequences, cells transfected with the DNA constructs, and methods of using the DNA constructs and transfected cells to provide for the controlled expression of structural genes, for the detection and recovery of transcriptional regulatory proteins, and for measuring the ability of compounds to act as agonist and antagonists of gene transcription.

Abstract: The present invention provides a nucleic acid-based therapeutic composition to treat an animal with disease by controlling the activity of effector cells, including T cells, macrophages, monocytes and/or natural killer cells, in the animal. The present invention also relates to methods of gene therapy involving different modes of administration of a therapeutic composition to treat animals with different types of diseases. Also included in the present invention are recombinant molecules for use in a therapeutic composition and recombinant cells useful as a tumor vaccine. Therapeutic compositions of the present invention include superantigen-encoding nucleic acid molecules, either in the presence or absence of a cytokine-encoding nucleic acid molecule, depending upon the disease being treated.

Abstract: One aspect of the invention relates to a phage-display library that expresses single-chain recombinant binding proteins. Inserts in the library comprise immunoglobulin heavy chain framework regions flanking highly divergent, synthetically produced hypervariable regions. A second aspect of the invention relates to the use of single-chain recombinant binding proteins to inhibit the activity of an intracellular constituent. In the exemplary case presented, the activity of intracellular glucose-6-phosphate dehydrogenase was inhibited by intracellular expression of a cloned single-chain recombinant binding protein.

Abstract: A method for detecting or quantitating a mutagenic substance in a sample includes culturing a host microorganism transformed with a recombinant gene comprising an SOS gene and genes expressing luciferase activity and optionally genes expressing an enzyme which catalyzes the production of a substrate for luciferase, positioned downstream of the SOS gene, in a medium to which the sample is added; and measuring a luminescence generated by expression of the gene expressing luciferase activity. The method is sensitive, accurate and non-time consuming; and gene systems used for said method, i.e., a recombinant gene comprising an SOS gene expressed when a DNA is damaged and a gene expressing luciferase activity positioned downstream of the SOS gene, and a host microorganism transformed with said recombinant gene. Preferably the recombinant gene further comprises a gene expressing an enzyme which catalyses the production of a substrate for the luciferase in the down stream of the SOS gene.

Abstract: Methods are disclosed to identify differentially expressed genes. In one aspect, one uses subtractive hybridization to enrich for candidate genes, followed by a PCR amplified radiolabeled display of cDNA products of the hybridization. Specially modified primer binding regions are used that can be achieved either through use of trimming plasmids or non-symmetric display plasmids.

Abstract: The invention relates to transgenic non-human mammals characterized in that the genome of said mammals contain at least one heterologous gene encoding for the production of heterologous catalytic entity selected from the group consisting of enzymes and antibodies, and wherein said catalytic entity produces a second heterologous product in the milk of said mammal. Especially useful in the practice of the invention are human glycosyltransferases and transgenic sheep, goats and cows. The heterologous product includes oligosaccharides and glycoconjugates.

Abstract: Vectors, or naked DNA, containing a promoter for an FSP1 gene and a downstream gene capable of attenuating fibroblasts and their function are provided. Methods of using these vectors to inhibit tissue injury related to fibrogenesis are also provided.