Abstract: The present invention provides an isolated nucleic acid sequence encoding murine IL-2R.gamma.. The present invention also provides a vector comprising a mutated IL-2R.gamma. nucleic acid which is capable of homologous recombination in at least some cells to which the vector is introduced. The present invention also provides an embryonic stem cell comprising a mutated IL-2R.gamma. nucleic acid integrated into the cell by homologous recombination following transfection with the vector above. The present invention further provides a blastocyst cell comprising the embryonic stem cell above. In addition, the present invention provides a transgenic animal comprising a mutated IL-2R.gamma. gene. In particular, the animal is a non-human mammal whose germ and somatic cells contain a mutated IL-2R.gamma. gene sequence introduced into said mammal, or an ancestor thereof, at an embryonic stage.

Abstract: The invention pertains to a novel method and construct for regulating gene expression through inhibition of gene expression by nuclear antisense RNA. The construct provides an efficient means for introducing, expressing and accumulating the antisense RNA in the nucleus. The antisense RNA hybridizes to the sense mRNA in the nucleus, thereby preventing both processing and cytoplasmic transport. The construct comprises a promoter, antisense sequences, and a cis- or trans-ribozyme which generates 3'-ends independently of the polyadenylation machinery and thereby inhibits the transport of the RNA molecule to the cytoplasm. The construct may also comprise a histone stem-loop structure that assists in stabilizing the transcripts against exonucleolytic degradation.

Abstract: A method and kit for detecting toxins and pollutants is disclosed. The kit includes a transgenic organism having a stress-inducible control region linked to a gene encoding a detectable protein wherein said control region regulates the expression of said detectable protein; exposing said organism to said sample; and determining the amount of detectable protein produced. Exposure of this organism to a toxin or pollutant induces the production of the detectable protein which can be easily measured. This invention provides a rapid and reliable system for testing samples for the presence of toxins or pollutants.

Abstract: A method for the protection of plants against pathogens, wherein a polynucleotide sequence comprising at least a sequence of a pathogenic avirulence gene (E) encoding a specific elicitor protein molecule (e) or a portion thereof is introduced into the genome of a plant containing a corresponding resistance gene (R), in which genes (E) and (R) are regulated in such a manner that simultaneous expression of said genes only occurs at the site of infection and said simultaneous expression can be induced by a broad range of pathogens. A polynucleotide sequence comprising at least a sequence of an avirulence gene (E) from a plant pathogen encoding a specific elicitor protein molecule (e) or a portion thereof, and a plant promoter (P) that can be induced by a broad range of pathogens and which permits expression at the site of infection only. Plant obtainable by use of said method and plant comprising said polynucleotide sequence.

Abstract: A DNA fragment for directing the expression of foreign or endogenous genes or RNA in cells of monocot plants. The fragment comprises a sequence corresponding to a first part of a putative type I starch branching enzyme gene (wbeI) present in wheat and a 5'-region upstream of the gene, or a part of the sequence that is effective for increasing the expression of the foreign or endogenous gene in the plant cells. The indicated sequence contains two promoter regions, P1 and P2. A DNA fragment effective to increase expression comprises at least one of the promoter regions, or an effective part. The fragment can be obtained from a genomic library of wheat and can be fused to suitable genes and markers and inserted into suitable vectors for expression in transgenic monocot plants.

Abstract: The invention provides a polynucleotide in substantially isolated form which comprises a contiguous sequence of nucleotides which is capable of selectively hybridizing to Seq. ID No. 1 or to the complement of Seq. ID No. 1, and a polypeptide in substantially isolated form which comprises: (a) the protein of Seq. ID No. 2; or (b) an allelic variant or species homologue thereof; or c) a protein at least 70% homologous to (a); or (d) a fragment of any one of (a) to (c) capable of forming a complex with the E2F-1 protein or related family member; or (e) a fragment of any one of (a) to (c) of at least 15 amino acids.

Abstract: Isolated nucleic acid molecules encoding a novel protein, NIP45, that interacts with members of the Nuclear Factor of Activated T cell (NF-AT) family of proteins, are disclosed. The invention further provides antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals carrying a NIP45 transgene. The invention further provides isolated NIP45 proteins and peptides, NIP45 fusion proteins and anti-NIP45 antibodies. Methods of using the NIP45 compositions of the invention are also disclosed, including methods for detecting NIP45 protein or mRNA in a biological sample, methods of modulating NIP45 activity in a cell, and methods for identifying agents that modulate an interaction between NIP45 and an NF-AT family protein.

Abstract: A method for the production of monoclonal antibodies in mammal's milk through the creation of transgenic animals that selectively express foreign antibody genes in mammary epithelial cells.

Abstract: Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile.

Abstract: The present invention provides DNA fragments derived from the 5' and 3' flanking regions of K18 gene which contain transciptional regulatory regions capable of conferring integration site independent and copy number dependent expression on a transgene when co-integrated 5' and 3' of the transgene. The present invention also provides vectors containing these DNA fragments, and transgenic animals containing the vectors.

Abstract: A composition for genetic manipulation which comprises a liposome comprised of lipid material, and adeno-associated viral (AAV) material. Typically, the AAV material is plasmid, and comprises a terminal repeat of the AAV genome. Methods are disclosed for introducing genetic material into cells by use of AAV liposomes. Accordingly, genetic material was introduced and integrated into stem cells, T cells, primary tumor cells, or tumor cell lines.

Abstract: Methods and compositions relating to chimeric genes containing (i) a tissue-specific promoter and (ii) a hypoxia response enhancer element, both of which are operably linked to a selected gene, such as a reporter gene, therapeutic gene (e.g., bcl-2, NOS, catalase and SOD), or deleterious gene are disclosed. Expression of the selected gene is enhanced in the target tissue under hypoxic conditions, such as conditions encountered during episodes of ischemia and reperfusion. The methods and compositions may be used as therapeutics and/or diagnostics.

Abstract: A DNA sequence for the gene therapy of tumors is described. In its essential elements, the DNA sequence is composed of an activator sequence, a promoter module and a gene for the active substance. The activator sequence is activated, in a cell-specific manner, in proliferating endothelial cells or in cells which are adjacent to these endothelial cells. This activation is regulated by the promoter module in a cell cycle-specific manner. The active substance is an inhibitor of angiogenesis or a cytostatic or cytotoxic molecule. The DNA sequence is inserted into a viral or non-viral vector which is supplemented with a ligand which possesses affinity for the activated endothelial cell.

Abstract: The invention includes recombinant DNA regulatory elements which control expression of the CD19 gene in a B-lineage-restricted manner.

Abstract: An assay for monitoring and assessing the mutagenic potential of agents which involves creating transgenic non-human animals carrying a test DNA sequence or sequences that can be quickly recovered and examined for mutations following exposure to one or more suspected mutagenic agents.

Abstract: A process for production of an exogenous gene or its product in a plant cell which comprises: inserting into a genome of plant,i) cDNA of replicase gene from an RNA plant virus, andii) cDNA of a recombinant virus genomic RNA inwhich coat protein gene is wholly or partly replaced with desired exogenous gene, orinoculating said recombinant virus genomic RNA on a plant cell having cDNA of replicase gene inserted in the genome. The process of the present invention enables to efficiently produce the desired exogenous gene product in plant cells in large quantities.

Abstract: The present invention relates to a method of conferring resistance against fire blight to pomaceous fruit scion or rootstock cultivars by transforming such cultivars with a gene which encodes for lytic proteins. Such transformation can be effected by bacterial infection or propulsion of particles into cell interiors. Once transformation has taken place, the cultivar is regenerated to a transgenic pomaceous fruit tree. This technique is particularly useful in treating apple and pear cultivars.

Abstract: Disclosed are methods of reducing neovascularization and of treating various disorders associated with neovascularization. These methods include administering to a tissue or subject a synthetic oligonucleotide specific for vascular endothelial growth factor nucleic acid effective in inhibiting the expression of vascular endothelial growth factor.

Abstract: Methods for controlling transfection efficiency mediated by complexes of cationic species and genetic material by adjusting the amount of membrane-associated proteoglycans and optionally adjusting the plasma concentration of glycosaminoglycans. Transfection efficiency is controlled by the amount of membrane-associated proteoglycans in the cell to be transfected and also by the plasma concentration of glycosaminoglycans. By increasing the amount of membrane-associated proteoglycans in the cell, and optionally decreasing the plasma concentration of glycosaminoglycans, the transfection efficiency can be increased. By decreasing the amount of membrane-associated proteoglycans in the cell, and optionally decreasing the plasma concentration of glycosaminoglycans, the transfection efficiency can be decreased. Transfection efficiency can be controlled, whether performed in vivo, ex vivo, or in vitro.

Abstract: The present invention provides a vector comprising an enhancer element and a nuclear matrix association region inserted between an inverted terminal repeat of adeno-associated virus. The vector can further comprise a heterologous nucleic acid inserted into the vector. The present invention further provides a method for integration of a nucleic acid into the genome of a cell, comprising administering to the cell a vector comprising an enhancer element, a heterologous nucleic acid and a nuclear matrix association region, each inserted between an inverted terminal repeat of adeno-associated virus, thereby integrating the nucleic acid into the genome of the cell.