Abstract: The invention relates to overcoming anti-cancer therapy resistance in melanoma by regulation of the expression of tyrosinase related protein 2 (TYRP2). Treatment of melanoma with anti-cancer therapy may be negatively impacted by anti-cancer resistance of melanoma cells. Altering expression of TYRP2 in melanoma cells can enhance efficacy of anti-cancer therapies, such as chemotherapy and radiotherapy. Methods for treatment of melanoma are disclosed, as well as methods for diagnosis of anti-cancer therapy resistance, and methods for evaluating candidate anti-cancer therapies for melanoma. Down-regulation of TYRP2 expression or activity can be accomplished using a genetic therapy such as antisense therapy, or by using small molecules which regulate TYRP2.

Abstract: This invention relates to oligonucleotides complementary to the thioredoxin and thioredoxin reductase genes which modulate tumor cell growth in mammals. This invention is also related to methods of using such compounds in inhibiting the growth of tumor cells in mammals. This invention also relates to pharmaceutical compositions comprising a pharmaceutically acceptable excipient and an effective amount of a compound of this invention.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of SAP-1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding SAP-1. Methods of using these compounds for modulation of SAP-1 expression and for treatment of diseases associated with expression of SAP-1 are provided.

Abstract: The present invention relates to the identification of a number of human genes as cellular targets for the design of therapeutic agents for suppressing human immunodeficiency virus infection. These genes encode products which appear to be necessary for HIV replication, as evidenced by an inhibition of HIV infection in cells in which the expression of these genes is down-regulated. In addition, the invention also relates to methods for identifying additional cellular genes as therapeutic targets for suppressing HIV infection, and methods of using such cellular genes and their encoded products in screening assays for selecting additional inhibitors of HIV.

Abstract: The invention provides diagnostic assays for assessing the sensitivity or resistance to DNA damaging agents and microtubule-directed chemotherapeutic drugs of malignant cells in a tumor or tissue. The assay provided involves determining gene expression levels of kinesin genes in the malignant cells, wherein under-expression of kinesin is found in cells resistant to DNA damaging agents and sensitive to microtubule-directed chemotherapeutic drugs, and over-expression of kinesin is found in cells sensitive to DNA damaging agents and resistant to microtubule-directed chemotherapeutic drugs.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of PKA regulatory subunit RII alpha. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PKA regulatory subunit RII alpha. Methods of using these compounds for modulation of PKA regulatory subunit RII alpha expression and for treatment of diseases associated with expression of PKA regulatory subunit RII alpha are provided.

Abstract: A process is provided of introducing an RNA into a living cell to inhibit gene expression of a target gene in that cell. The process may be practiced ex vivo or in vivo. The RNA has a region with double-stranded structure. Inhibition is sequence-specific in that the nucleotide sequences of the duplex region of the RNA and of a portion of the target gene are identical. The present invention is distinguished from prior art interference in gene expression by antisense or triple-strand methods.

Abstract: A method for identifying an antisense oligonucleotide capable of binding to a target mRNA, which comprises contacting the target mRNA with each member of an oligonucleotide library separately under hybridization conditions, removing unhybridized material and determining which member or members hybridize; wherein the oligonucleotide library comprises a plurality of distinct nucleotide sequences of a predetermined common length, and wherein each nucleotide sequence comprises a known sequence of 4 to 8 bases and all possible combinations of the known sequence are present in the library.

Abstract: An enzymatic RNA molecule which cleaves mRNA associated with development or maintenance of lung cancer.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Cyclin D2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Cyclin D2. Methods of using these compounds for modulation of Cyclin D2 expression and for treatment of diseases associated with expression of Cyclin D2 are provided.

Abstract: The present invention provides a method of treating or preventing the inflammatory response of an inflammatory bowel disease in a subject, comprising administering to the subject an amount of a STAT-4 antisense oligonucleotide effective in treating or preventing the inflammatory response of the inflammatory bowel disease.

Abstract: In a preferred aspect of the invention, the upstream sequences of the TIGR protein encoding sequence can be used to diagnose a sensivity to steroids and a risk for glaucoma or ocular hypertensive disorders. Methods, kits, and nucleic acids containing polymorphisms, base substitutions, or base additions located within the upstream region and within protein-encoding regions of the TIGR gene are also provided. The upstream sequences disclosed, including the TIGR promoter regions and those regions possessing functional characteristics associated with or possessed by the TIGR gene 5′regulatory region, can also be used to generate cells, vectors, transgenic animals, and nucleic acid constructs useful in a variety of diagnostic and prognostic methods and kits as well as therapeutic compounds, compositions, and methods.

Abstract: The present invention relates to novel therapeutic and diagnostic arrays. More particularly, the present invention is directed to dendrimer based multifunctional compositions and systems for use in disease diagnosis and therapy (e.g., cancer diagnosis and therapy). The compositions and systems generally comprise two or more separate components for targeting, imaging, sensing, and/or triggering release of a therapeutic or diagnostic material and monitoring the response to therapy of a cell or tissue (e.g., a tumor).

Abstract: Antisense-oligonucleotides or effective derivatives thereof hybridizing with an area of a gene coding for transforming growth factor-&bgr; (TGF-&bgr;) comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID NO. 1-56 and 137 or comprising the following nucleic acid sequences identified in the sequence listing under SEQ ID NO. 57 to 136 each of the nucleic acids having a DNA- or RNA-type structure.

Abstract: A method of inhibiting activities of a tRNA of a selected pathogen is provided wherein a cell infected with a selected pathogen is contacted with an effective amount of an oligonucleotide targeted to a region of the cloverleaf structure of a tRNA of the selected pathogen. Compositions for inhibiting activities of a tRNA of a selected pathogen which contain an oligonucleotide targeted to a region of cloverleaf structure of a tRNA of the selected pathogen are also provided. In addition, methods of killing the pathogen with these compositions are provided.

Abstract: This invention provides methods for screening a modulating agent which when combined with antitumor therapeutic agent increases apoptosis in tumor cells. This invention also provides methods for screening antitumor therapeutic agents suitable for combination therapy with a protein kinase C inhibitors capable of potentiating apoptosis in tumor cells. This invention further provides different combination therapies comprising the specific protein kinase C inhibitors and the antitumor therapeutic agents.

Abstract: Compositions and methods for modulating cell cycle and cell proliferation are provided. Additionally the compositions find use in enhancing disease resistance and increasing transformation efficiency in plants. The method involves transforming a plant with a sense or antisense prohibitin sequence. The prohibitin sequence acts to regulate cell division in the plant cell. Transformed plants, plant cells, tissues, and seed are also provided having enhanced disease resistance.

Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of RECQL4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding RECQL4. Methods of using these compounds for modulation of RECQL4 expression and for treatment of diseases associated with expression of RECQL4 are provided.

Abstract: Compositions and methods are provided for modulating the expression of TGF-&bgr;. Antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding TGF-&bgr; are preferred. Methods of using these compounds for modulation of TGF-&bgr; expression and for treatment of diseases associated with expression of TGF-&bgr; are also provided. Methods of sensitizing cells to apoptotic stimuli are also provided.

Abstract: Genetic modification or selection of avians requires that large numbers of birds be genetically analyzed for sequences of interest. Typically, DNA is extracted on an individual basis from samples taken from the birds. Current methods of DNA extraction extract the DNA from blood or other tissues using tedious and time-consuming procedures. The present invention provides a high throughput screening assay for detecting a genetic sequence in multiple samples. The assay further provides a DNA extraction method that allows DNA to be extracted rapidly from multiple avian samples, such as red blood cells. The extraction method is extremely reliable and does not require that each sample be quantitated post-extraction. The extracted DNA can be used for a variety of genetic assays, including a high throughput screening assay to identify insertion of a transgene. The present invention is particularly useful for extracting DNA from nucleated RBCs.