Abstract: Disclosed herein are methods and compositions for enhancing gene targeting. The method entails co-administrating to a cell a targeting molecule and a means of enhancing the function of the targeting molecule upon delivery to the cell. The means of enhancing the function of the targeting molecule including one or more of a stressor that induces cellular stress, a proton sponge molecule, and an endosome or lysosome inhibitor. Compositions disclosed include a targeting molecule and one or more of a stressor that induces cellular stress, a proton sponge molecule, and an endosome or lysosome inhibitor.

Abstract: Disclosed herein are methods and compositions for enhancing gene targeting. The method entails co-administrating to a cell a targeting molecule and a means of enhancing the function of the targeting molecule upon delivery to the cell. The means of enhancing the function of the targeting molecule including one or more of a stressor that induces cellular stress, a proton sponge molecule, and an endosome or lysosome inhibitor. Compositions disclosed include a targeting molecule and one or more of a stressor that induces cellular stress, a proton sponge molecule, and an endosome or lysosome inhibitor.

Abstract: Disclosed herein are methods and compositions for enhancing gene targeting. The method entails co-administrating to a cell a targeting molecule and a means of enhancing the function of the targeting molecule upon delivery to the cell. The means of enhancing the function of the targeting molecule including one or more of a stressor that induces cellular stress, a proton sponge molecule, and an endosome or lysosome inhibitor. Compositions disclosed include a targeting molecule and one or more of a stressor that induces cellular stress, a proton sponge molecule, and an endosome or lysosome inhibitor.

Abstract: Provided herein are, inter alia, methods useful for delivering nucleic acids and kinase inhibitors to a cell. The methods provided herein include the delivery of therapeutic nucleic acids to cancer cells by contacting a cancer cell with a kinase inhibitor and a therapeutic nucleic acid. The methods provided herein are therefore, inter alia, useful for the treatment of cancer.

Abstract: A composition of phosphodiester oligonucleotides of various defined sizes has been created that mimics the effects of defibrotide. The composition essentially consists of mixtures of synthetic phosphodiester oligonucleotides comprising Nmers ranging from 40 mers to 65 mers. The phosphodiester oligonucleotides are preferably heteropolymers composed of either A, G, C, and T at each position but may also be homopolymers, i.e. the same base may be present at each position in the oligonucicotidc. These mixtures are effective in the treatment of cancer and other diseases.

Abstract: This invention provides an antisense oligonucleotide or analog thereof comprising 10 or more contiguous bases or base analogs from the sequence of bases of sequence A, B, C, D, E, F, G, H, I, J, K, L, or M of FIG. 1. This invention also provides the above-described antisense oligonucleotides, wherein the nucleotide sequence comprises nucleotide sequence A, A?, B, C, C?, D, E, E, E?, F, G, G?, H, H?, I, I?, J, K, K?, L, L?, M, or M? of FIGS. 2A and 2B. This invention also provides the above-described antisense oligonucleotides, wherein the oligonucleotide is encapsulated in a liposome or nanoparticle. This invention also provides the above-described antisense oligonucleotides, wherein the phosphate backbone comprises phosphorothioate bonds. In addition, this invention provides a method of treating cancer, comprising introducing into a tumor cell an effective amount of the the above-described antisense oligonucleotide, thereby reducing the levels of bcl-xL protein produced and treating cancer.

Abstract: The present invention provides a peptide that can complex with an oligonucleotide, e.g. an antisense oligonucleotide, and deliver it into a cell. The present invention also provides compositions comprising a complex of such a peptide and an oligonucleotide and methods of delivering an oligonucleotide into a cell and of inhibiting protein expression using such compositions. The present invention also provides a method of making such a complex, a method of sensitizing cells to anti-cancer agents such as paclitaxel, and pharmaceutical compositions.

Abstract: The present invention provides antisense phosphorothioate oligonucleotides that specifically inhibit the translation of heparanase. The invention also provides various methods of reducing angiogenesis and metastasis of tumors in a subject using said antisense phosphorothioate oligonucleotides. Finally the invention provides pharmaceutical compositions comprising the said antisense phosphorothioate oligonucleotides as active ingredients.

Abstract: The present invention provides a peptide that can complex with an oligonucleotide, e.g. an antisense oligonucleotide, and deliver it into a cell. The present invention also provides compositions comprising a complex of such a peptide and an oligonucleotide and methods of delivering an oligonucleotide into a cell and of inhibiting protein expression using such compositions. The present invention also provides a method of making such a complex, a method of sensitizing cells to anti-cancer agents such as paclitaxel, and pharmaceutical compositions.

Abstract: The present invention provides antisense phosphorothioate oligonucleotides that specifically inhibit the translation of heparanase. The invention also provides various methods of reducing angiogenesis and metastasis of tumors in a subject using said antisense phosphorothioate oligonucleotides. Finally the invention provides pharmaceutical compositions comprising the said antisense phosphorothioate oligonucleotides as active ingredients.

Abstract: This invention provides a nuclease-resistant external guide sequence (EGS) oligonucleotide selected from the group consisting of Inno-1405, Inno-1407 and Bcl-xL1 whose sequences are set forth in Table 1. This invention also provides a method of inducing specific intracellular mRNA cleavage through activation of RNase P comprising contacting a cell with a complex comprising an EGS oligonucleotide and a carrier. This invention provides methods of downregulating PKC-&agr; protein expression and PKC-&agr; mRNA expression comprising contacting a cell with a complex comprising an EGS oligonucleotide and a carrier. This invention provides methods of downregulating bcl-xL protein expression and bcl-xL mRNA expression comprising contacting a cell with a complex comprising an EGS oligonucleotide and a carrier.

Abstract: The present invention provides antisense phosphorothioate oligonucleotides that specifically inhibit the translation of heparanase. The invention also provides various methods of reducing angiogenesis and metastasis of tumors in a subject using said antisense phosphorothioate oligonucleotides. Finally the invention provides pharmaceutical compositions comprising the said antisense phosphorothioate oligonucleotides as active ingredients.

Abstract: The present invention provides a peptide that can complex with an oligonucleotide, e.g. an antisense oligonucleotide, and deliver it into a cell. The present invention also provides compositions comprising a complex of such a peptide and an oligonucleotide and methods of delivering an oligonucleotide into a cell and of inhibiting protein expression using such compositions. The present invention also provides a method of making such a complex, a method of sensitizing cells to anti-cancer agents such as paclitaxel, and pharmaceutical compositions.

Abstract: This invention provides an antisense oligonucleotide or analog thereof comprising 10 or more contiguous bases or base analogs from the sequence of bases of sequence A, B, C, D, E, F, G, H, I, J, K, L, or M of FIG. 1. This invention also provides the above-described antisense oligonucleotides, wherein the nucleotide sequence comprises nucleotide sequence A, A′, B, C, C′, D, E, E, E′, F, G, G′, H, H′, I, I′, J, K, K′, L, L′, M, or M′ of FIGS. 2A and 2B. This invention also provides the above-described antisense oligonucleotides, wherein the oligonucleotide is encapsulated in a liposome or nanoparticle. This invention also provides the above-described antisense oligonucleotides, wherein the phosphate backbone comprises phosphorothioate bonds.

Abstract: This invention provides an antisense oligonucleotide or analog thereof comprising 10 or more contiguous bases or base analogs from the sequence of bases of sequence A, B, C, D, E, F, G, H, I, J, K, L, or M of FIG. 1. This invention also provides the above-described antisense oligonucleotides, wherein the nucleotide sequence comprises nucleotide sequence A, A′, B, C, C′, D, E, E′, F, G, G′, H, H′, I, I′, J, K, K′, L, L′, M, or M′ of FIGS. 2A and 2B. This invention also provides the above-described antisense oligonucleotides, wherein the oligonucleotide is encapsulated in a liposome or nanoparticle. This invention also provides the above-described antisense oligonucleotides, wherein the phosphate backbone comprises phosphorothioate bonds.

Abstract: The present invention provides methods of stimulating or inhibiting intracellular phosphorylation of tyrosine by a heparin-binding receptor which comprises contacting a cell having on its surface the heparin-binding receptor with a phosphorothioate oligonucleotide moiety of suitable length and base composition, such phosphorothioate oligonucleotide moiety being present in an effective amount. The invention further provides a method of inhibiting the formation of blood vessels in a subject which comprises administering to the subject an amount of a phosphorothioate oligonucleotide moiety of suitable length and base composition. The invention also provides a method of inhibiting proliferation of cells having a malignant phenotype in a subject which comprises administering to the subject an amount of a phosphorothioate oligonucleotide moiety of suitable length and base composition.

Abstract: This invention provides methods of inhibiting proliferation, migration and heterotypic adhesion of vascular smooth muscle cells which comprise contacting the vascular smooth muscle cells with an amount of a phosphorothioate oligonucleotide moiety effective to inhibit the proliferation, migration or heterotypic adhesion of the vascular smooth muscle cells. This invention provides methods of inhibiting neointimal formation after balloon injury, percutaneous transluminal coronary angioplasty restenosis, and coronary artery stent restenosis in a subject which comprise administering to the subject an amount of a phosphorothioate oligonucleotide moiety effective to inhibit neointimal formation, percutaneous transluminal coronary angioplasty restenosis, or coronary artery stent restenosis in the subject. This invention further provides pharmaceutical compositions effective for treating the conditions recited above.

Abstract: Continuous cell lines have been established from adrenocortical corcinomas. The cell lines are maintained in fully defined serum-free, steroid-free mediums. The cells of the invention, as exemplified by NCI-H295 cells, express all of the major pathways of steroid-ogenesis, including formation of corticosteroids, mineralocorticoids and androgens.

Abstract: The present invention provides phosphorothioate oligonucleotide moieties comprising a phosphorothioate oligonucleotide comprising the sequence G.sub.m X.sub.n G.sub.p, wherein G is guanosine; X is thymidine, adenosine or cytidine, or a combination thereof; each of m, n and p is independently an integer greater than 2; the phosphorothioate oligonucleotide moiety being capable of binding to a V3 loop of HIV envelope glycoprotein. The invention further provides for a method of inhibiting HIV activity. The invention also provides for a method of inhibiting HIV activity in a subject. The invention further provides for a method of treating an HIV related disorder in a subject. Finally, the invention provides a pharmaceutical composition comprising a phosphorothioate oligonucleotide moiety and a pharmaceutically acceptable carrier.

Abstract: The present invention provides a method of treating glaucoma which comprises administering to a subject an effective amount of an oligonucleotide which may be substituted or modified in its phosphate, sugar, or base, so as to decrease intraocular pressure and thereby treat the glaucoma.