Abstract: The present invention concerns oligonucleotides containing one or more modified nucleotides which increase the binding affinity of the oligonucleotides to target nucleic acids having a complementary nucleotide base sequence. These modified oligonucleotides hybridize to the target sequence at a faster rate than unmodified oligonucleotides having an identical nucleotide base sequence. Such modified oligonucleotides include oligonucleotides containing at least one 2?-O-methylribofuranosyl moiety joined to a nitrogenous base. Oligonucleotides can be modified in accordance with the present invention to preferentially bind RNA targets. The present invention also concerns methods of using these modified oligonucleotides and kits containing the same.

Abstract: The HIV regulatory proteins Tat and Rev accumulate in nucleoli of human cells. No functional role has been attributed to this localization. Recently it was demonstrated that expression of Rev induces nucleolar re-localization of some nuclear factors involved in Rev export. Thus, it is likely that the nucleolus plays a critical role in Rev-mediated export of singly spliced and unspliced HIV-1 RNAs. As a test for trafficking of HIV-1 RNAs into the nucleolus, a hammerhead ribozyme which specifically cleaves HIV-1 RNA was joined to the U16 snoRNA resulting in accumulation of the ribozyme within nucleoli of human cells. Stably transduced human T-cells expressing this nucleolar localized ribozyme dramatically suppressed HIV-1 replication, confirming a possible trafficking of the HIV RNA through the nucleoli of human cells. In addition, a TAR element which binds Tat was joined to the U16 snoRNA, also resulting in localization in the nucleoli and inhibiting HIV replication.

Abstract: A circular DNA molecule, useful for gene therapy, comprising at least one nucleic acid sequence of interest, characterized in that the region allowing the replication thereof has an origin of replication with a functionality in a host cell that requires the presence of at least one specific protein foreign to said host cell. A method for preparing same, cells incorporating said DNA molecules and uses thereof in gene therapy are also described.

Abstract: Methods for the identification of compounds which modulate, either inhibit or stimulate, biomolecules are provided. Nucleic acids, especially RNAs are preferred substrates for such modulation. The present methods are particularly powerful in that they provide novel combinations of techniques which give rise to compounds, usually “small” organic compounds, which are highly potent modulators of RNA and other biomolecular activity. In accordance with preferred aspects of the invention, very large numbers of compounds may be tested essentially simultaneously to determine whether they are likely to interact with a molecular interaction site and modulate the activity of the biomolecule. Pharmaceuticals, veterinary drugs, agricultural chemicals, industrial chemicals, research chemicals and many other beneficial compounds may be identified in accordance with embodiments of this invention.

Abstract: The invention relates to the modulation of gene expression. In particular, the invention relates to compositions comprising antisense oligonucleotides which inhibit expression of a gene in operable association with protein effectors of a product of that gene, and methods of using the same. In addition, the invention relates to the modulation of mammalian gene expression regulated by methylation.

Abstract: The present invention provides for a method of culturing cells and inducing the expression of at least one gene in the cell culture. The method provides for contacting the cell with a transcription factor decoy oligonucleotide sequence directed against a nucleotide sequence encoding a shear stress response element.

Abstract: An allergen-free transgenic peanut seed is produced by recombinant methods. Peanut plants are transformed with multiple copies of each of the allergen genes, or fragments thereof, to suppress gene expression and allergen protein production. Alternatively, peanut plants are transformed with peanut allergen antisense genes introduced into the peanut genome as antisense fragments, sense fragments, or combinations of both antisense and sense fragments. Peanut transgenes are under the control of the 35S promoter, or the promoter of the Ara h2 gene to produce antisense RNAs, sense RNAs, and double-stranded RNAs for suppressing allergen protein production in peanut plants. A full length genomic clone for allergen Ara h2 is isolated and sequenced. The ORF is 622 nucleotides long. The predicted encoded protein is 207 amino acids long and includes a putative transit peptide of 21 residues. One polyadenilation signal is identified at position 951. Six additional stop codons are observed.

Abstract: A chimeric peptide-nucleic acid construct is disclosed; the peptide portion directs entry of the construct into mitochhondria.

Abstract: The present invention concerns oligonucleotides containing one or more modified nucleotides which increase the binding affinity of the oligonucleotides to target nucleic acids having a complementary nucleotide base sequence. These modified oligonucleotides hybridize to the target sequence at a faster rate than unmodified oligonucleotides having an identical nucleotide base sequence. Such modified oligonucleotides include oligonucleotides containing at least one 2?-O-methylribofuranosyl moiety joined to a nitrogenous base. Oligonucleotides can be modified in accordance with the present invention to preferentially bind RNA targets. The present invention also concerns methods of using these modified oligonucleotides and kits containing the same.

Abstract: The present invention relates generally to a method for the prophylaxis and/or treatment of skin disorders, and in particular proliferative and/or inflamatory skin disorders, and to genetic molecules useful for same. The present invention is particularly directed to genetic molecules capable of modulating growth factor interaction with its receptor on epidermal keratinocytes to inhibit, reduce or otherwise decrease stimulation of this layer of cells. The present invention contemplates, in a most preferred embodiment, a method for the prophylaxis and/or treatment of psoriasis.

Abstract: This invention concerns methods for identifying A2B adenosine receptor agonists and antagonists as well as methods for using A2B adenosine receptor antagonists to treat cell proliferation orders mediated by the A2B adenosine receptor.

Abstract: The present invention is directed to the identification and use of ribonucleoside analogs to induce the mutation of an RNA virus, including BVDV, HIV and HCV, or a virus which otherwise replicates through an RNA intermediate. The increase in the mutation rate of the virus results in reduced viability of progeny generations of the virus, thereby inhibiting viral replication. In addition to these methods and related compositions, the invention provides methods and combinatorial chemistry libraries for screening ribonucleoside analogs for mutagenic potential.

Abstract: This invention is directed to nucleic acids which encode the proteins that direct the synthesis of the orthosomycin everninomicin and to use of the nucleic acids and proteins to produce compounds exhibiting antibiotic activity based on the everninomycin structure. The DNA sequence for the gene clusters responsible for encoding everninomicin biosynthetic genes, which provide the machinery for producing everninomicin, are provided. Thus, this invention provides the nucleic acid sequences needed to synthesize novel everninomicin-related compounds based on everninomicin, arising from modifications of the DNA sequence designed to change glycosyl and modified orsellinic acid groups contained in everninomicin. A. Micromonospora site-specific integrase gene is also provided, which can be incorporated in a vector for integration into any actinomycete, and, particularly into Monospora.

Abstract: The present invention relates to the fields of biology, genetics and medicine. In particular it concerns new methods for the detection, characterization and/or treatment (or management) of neuro degenerative diseases, particularly amyotrophic lateral sclerosis.

Abstract: A transcribed non-naturally occurring RNA molecule comprising a desired RNA molecule, wherein the 3? region of the RNA is able to base-pair with at least 8 bases at the 5? terminus of the same RNA molecule.

Abstract: A versatile modular peptide mediated intracellular delivery system is disclosed which may be particularly adapted to facilitate the delivery of therapeutic compounds which are large in size or complex in nature. The invention relates both to a modular peptide mediated intracellular delivery system and a method of delivering a compound into a cell using the system.

Abstract: The present invention relates to all facets of novel polynucleotides, the polypeptides they encode, antibodies and specific binding partners thereto, and their applications to research, diagnosis, drug discovery, therapy, clinical medicine, forensic science and medicine, etc. The polynucleotides are differentially-regulated in prostate cancer and are therefore useful in variety of ways, including, but not limited to, as molecular markers, as drug targets, and for detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, determining predisposition to, etc., diseases and conditions, to prostate cancer.

Abstract: The present invention relates to a method of screening for compounds that inhibit the virulence of Pseudomonas bacteria and comprises the steps of: providing a culture medium comprising Pseudomonas bacteria, administering a test compound to said bacteria, and then detecting the presence or absence of inhibition of the catabolite repression control (Crc) protein in the bacteria. The inhibition of the Crc protein indicates that the compound has antivirulence activity against Pseudomonas bacteria. Antisense oligonucleotides that inhibit expression of the Crc protein in a Pseudomonas bacteria and is nuclease resistant are also disclosed. Antivirulence compounds and the uses thereof in treating Pseudomonas infections are also disclosed.

Abstract: The present invention relates to the use of antisense oligonucleotides directed against specific nucleic acid sequences coding for receptors, alone or in combination, in order to inhibit the inflammatory reaction that is present in asthma, atopy or hypereosinophilia and to inhibit neoplastic cell proliferation. The antisense oligonucleotides of the present invention are used for treating and/or preventing asthma, allergy, hypereosinophilia, general inflammation or cancer. The oligonucleotides of the present invention are more specifically directed against nucleic acid sequences coding for a CCR3 receptor, a common subunit of IL-4 and IL-13 receptors, or a common sub-unit of IL-3, IL-5 and GM-CSF receptors.

Abstract: As described herein, the present invention comprises a method for using tubedown-1 (tbdn-1) antisense reagents as gene therapy agents for the treatment of bone tumors and Ewing's sarcoma family of tumors. Antisense-based reagents, such as tbdn-1 antisense construct or biologically stabilized oligonucleotides, or any compound which would elicit the downregulation of tbdn-1 level or activity and the same biological effects as tbdn-1 antisense construct on bone tumor growth in vivo provide valuable alternative or supplemental therapies for bone cancer.