Abstract: The present invention relates to bi-directional nucleic acid ligand compounds wherein at least two oligonucleotides of opposite sequence polarity are linked to a connecting compound at their same respective terminii; either the 5' terminii or the 3 ' terminii. These compounds are useful for binding protein or small molecule targets and thus may be used as diagnostic or therapeutic agents.

Abstract: The present invention relates to bi-directional nucleic acid ligand compounds wherein at least two oligonucleotides of opposite sequence polarity are linked to a connecting compound at their same respective terminii; either the 5' terminii or the 3' terminii. These compounds are useful for binding protein or small molecule targets and thus may be used as diagnostic or therapeutic agents.

Abstract: The striated muscle of the tongue of an animal (in particular, a mammal) is employed as the target tissue for direct DNA injection of an exogenous polynucleotide sequence encoding a biologically active molecule. The DNA is incorporated into the tongue muscle cells and the polypeptide encoded thereby expressed, resulting in the production of a biologically active molecule. Superior levels of expression of the injected exogenous polynucleotide are achieved relative to injection in other types of cells, in particular other types of muscle cells. Moreover, the striated muscle of the tongue represent an easily accessed anatomic location that has not previously been used for direct DNA injection.

Abstract: The present invention provides a recombinant plasmid comprising combining a hybrid plasmid vector with the isolated DNA sequences of one or more genes encoding nitrile degrading enzymes which are derived from bacteria belonging to the genus Rhodococcus, said hybrid plasmid vector comprising an isolated DNA sequence which confers on the vector the ability to replicate and amplify in the cells of bacteria belonging to the genus Rhodococcus, and an isolated DNA sequence which confers on the vector the ability to replicate and amplify in the cells of bacteria belonging to Escherichia coli, and an isolated DNA sequence containing a drug resistance gene.

Abstract: Antisense oligonucleotides and composition of oligonucleotides are taught which inhibit the proliferation of cells without affecting cell viability. p53 antisense oligonucleotides are shown to inhibit the proliferation of tissue culture cells expressing this gene. Methods of treating a patient with such antisense oligonucleotides is described.

Abstract: Leukemias characterized by the presence of the Philadelphia chromosome and the expression of the hybrid bcr-abl gene are treated with antisense oligonucleotides complementary to a target sequence of the bcr-abl mRNA transcript including the breakpoint junction. Individual chronic myelogoneous leukemia patients or Philadelphia chromosome-positive acute lymphocytic leukemia patients are treated by first sequencing the individual's bcr-abl breakpoint junction, and then administering antisense oligonucleotides complementary thereto. The oligonucleotides are designed to hybridize specifically to the bcr-abl breakpoint junction without substantial cross hybridization to untranslocated c-abl sequences. Treatment may comprise in vivo administration of antisense oligonucleotides, or ex vivo treatment such as bone marrow purging.

Abstract: The invention described here is a method whereby a molecular tag is put on a gene, transcript and protein in a single recombinational event. The protein tag takes the form of a unique peptide that can be recognized by an antibody or other specific reagent, the transcript tag takes the form of the sequence of nucleotides encoding the peptide that can be recognized by a specific polynucleotide probe, and the gene tag takes the form of a larger sequence of nucleotides that includes the peptide-encoding sequence and other associated nucleotide sequences. The central feature of the invention in its essential form is that the tag-creating DNA has a structure such that when it is inserted into an intron within a gene it creates two hybrid introns separated by a new exon encoding the protein tag. A major virtue of the method is that it allows one to identify new proteins or protein-containing structures, and, having done so, to readily identify and analyze the genes encoding those proteins.

Abstract: Methods of genetically modifying donor cells by gene transfer for grafting into the central nervous system to treat defective, diseased or damaged cells are disclosed. The modified donor cells produce functional molecules that effect the recovery or improved function of cells in the CNS. Methods and vectors for carrying out gene transfer and grafting are described.

Abstract: Methods and pharmaceutical compositions for modifying the mesothelial cells of a mammalian recipient in situ are provided. The methods include forming a mesothelial cell expression system in vivo or ex vivo and administering the expression system to the mammalian recipient (by way of the body cavities normally lined by mesothelial cells). The mesothelial cell expression system is useful for the localized and systemic delivery of therapeutic agents in situ.

Abstract: The invention provides a method for synthesizing new and useful single-stranded DNAs which have a stem-loop configuration (ss-slDNA). The method is an in vivo or in vitro synthesis. Replicating vehicles are provided which produce these ss-slDNAs. The slDNAs can be used for introducing random mutations in a selected gene, and they lend themselves for replication by a variant of the PCR method.

Abstract: The present invention provides a bcl-2 gene inhibitory element (BIE), which can inhibit expression of a gene in position-dependent and orientation-dependent manner. The invention provides, for example, BIE-1, having the nucleotide sequence 5'-CAAGAATGCAA-3' (SEQ ID NO: 1), which acts in an orientation-dependent and position-dependent manner to down-regulate the expression of the bcl-2 gene. The invention also provides a BIE binding factor (BBF), which is a cellular factor that can bind to a BIE. The invention provides, for example, BBF-A, which binds to BIE-1, including a nucleic acid sequence (SEQ ID NO: 8) encoding a portion of the amino acid sequence (SEQ ID NO: 9) of BBF-A. The invention further provides an antibody that specifically binds BBF-A. The invention also provides screening assays for identifying agents that can increase or decrease the binding of a BBF to a BIE, modulate the expression of a nucleic acid molecule linked to a BIE or modulate apoptosis in a cell.

Abstract: The present invention relates to promoter elements from human type I transglutaminase (TGase I) genes for controlled gene expression of both human TGase I and heterologous proteins. These promoter elements permit tissue-specific expression of genes, e.g. for use in human gene therapy and for testing pharmaceutical agents with artificial skin. Additionally, the subject promoter elements can provide differential regulation under physiological conditions or in the presence of exogenously added factors including calcium and retinoic acid.

Abstract: A method of stimulating pigment production in mammalian skin, as well as protecting mammalian skin against ultraviolet damage, is disclosed. Also disclosed is a method of stimulating pigment production in mammalian cells, a method of stimulating melanogenesis in mammalian melanocytes, and a culture medium for stimulating melanin production. Preparations useful in the present methods are additionally disclosed. The methods comprise administering to the epidermis or to the cells DNA fragments, either single- or double-stranded, or a mixture of both, or deoxynucleotides, dinucleotides, or dinucleotide dimers, in an appropriate vehicle, such as a liposomal preparation or propylene glycol. The preparations include DNA fragments, deoxynucleotides, dinucleotides, or dinucleotide dimers and an appropriate delivery vehicle, such as liposomes or a propylene glycol. The DNA fragments, deoxynucleotides, or dinucleotides used in the methods or in the preparations can be ultraviolet-irradiated.

Abstract: The invention relates to a cloned region of the Bordetella pertussis genome located 3' of the ptx operon encoding factors required for expression, assembly and secretion of pertussis holotoxin. Methods for obtaining increased levels of holotoxin production using homologous and heterologous hosts are also described.

Abstract: Disclosed is the in vitro development of mammalian embryos to the implantation stage by culturing the embryos in a medium containing leukemia inhibitory factor (LIF).

Abstract: Hormone receptors and the transcription factor Jun/AP-1 have been shown to reciprocally repress one another by a mechanism which is independent of DNA binding. For example, over-expression of AP-1 represses glucocorticoid-induced activation of genes carrying a functional glucocorticoid response element. Conversely, glucocorticoid has been shown to repress the transcriptional activation of genes which are controlled by promoters which contain the AP-1 binding site. In addition, methods are disclosed for selecting compounds useful for treating cells undergoing uncontrolled proliferation, such compounds being capable of disrupting the function of AP-1, but display substantially no ability to promote the transcriptional activation of hormone responsive genes.

Abstract: Xenogeneic tissue is introduced into an immunocompromised host for interacting with agents and using such interaction for evaluating efficacy of drugs and vaccines, producing xenogeneic monoclonal antibodies, evaluating the effect of the various agents on specific tissues and the like. Particularly, drugs can be evaluated for their efficacy against a wide variety of pathogens which infect xenogeneic tissue, agents can be evaluated for their effect on the xenogeneic immune system and monoclonal antibodies to a predetermined epitope may be produced.

Abstract: Methods for identifying oligonucleotides having a desired activity in vivo are disclosed. In accordance with preferred embodiments, oligonucleotides capable of conferring a desired phenotype are identified. Therapeutic, diagnostic and research methods and compositions employing such oligonucleotides are provided. Prior knowledge of the sequence or structure of a target molecule is generally not required.

Abstract: Biological effects of agents for diagnostic or therapeutic use are evaluated by administration of the agents to transgenic animals which are transformed with heterologous DNA and which are immune tolerant to the expression product of the heterologous DNA. In a further embodiment, preparations that are immunogenic in the transgenic animal model are purified by reverse immunoaffinity chromatography on antibody obtained from responding transgenic animals.

Abstract: Chimeric immunocompromised hosts are provided, comprising human bone marrow of at least 4 weeks from the time of implantation. The bone marrow is found to assume the normal population of bone marrow except for erythrocytes. The bone marrow may be used to study the effect of various agents on the proliferation and differentiation of hematopoietic cells.