Abstract: The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

Abstract: The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

Abstract: The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

Abstract: The present invention provides molecular switch system methods and compositions for use in regulatable gene expression. The system includes a nucleic acid construct which has a DNA response sequence for a transcriptional regulatory protein operably linked to a promoter, a compound binding sequence in the vicinity of the DNA response sequence, a transgene under the control of the promoter; and a DNA binding compound. In some cases, the molecular switch system further includes a nucleic acid sequence encoding a transcriptional regulatory protein operably linked to a second promoter. The invention further provides a method for screening compounds for the ability to function in the molecular switch system and thereby regulate gene expression.

Abstract: This invention provides nucleic acid sequences, vectors and host cells comprising regulatory regions associated with various promoters including a cyclin D1 promoter, a CD40L promoter, three HBV promoters (core, pre-S1 and HBV-X), a vancomycin-resistant enterococci (VRE) promoter, an androgen receptor promoter, a Her2 promoter, and ?-lactamase promoter. The invention further provides methods of regulating gene expression comprising the regulatory regions of such promoters.

Abstract: The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

Abstract: The present invention relates to novel nucleoside 5′-monophosphate mimics, which contain novel nucleoside bases and phosphate moiety mimics optionally having sugar-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, anticancer, and immunomodulatory agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

Abstract: This invention provides nucleic acid sequences, vectors and host cells comprising regulatory regions associated with various promoters including a cyclin D1 promoter, a CD40L promoter, three HBV promoters (core, pre-S1 and HBV-X), a vancomycin-resistant enterococci (VRE) promoter, an androgen receptor promoter, a Her2 promoter, and &bgr;-lactamase promoter. The invention further provides methods of regulating gene expression comprising the regulatory regions of such promoters.

Abstract: Antisense oligonucleotides are provided which are complementary to and hybridizable with at least a portion of HCV RNA and which are capable of inhibiting the function of the HCV RNA. These oligonucleotides can be administered to inhibit the activity of Hepatitis C virus in vivo or in vitro. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus, and for diagnosis and detection of HCV and HCV-associated diseases. Methods of using these compounds are also disclosed.

Abstract: Antisense oligonucleotides are provided which are complementary to and hybridizable with at least a portion of HCV RNA and which are capable of inhibiting the function of the HCV RNA. These oligonucleotides can be administered to inhibit the activity of Hepatitis C virus in vivo or in vitro. These compounds can be used either prophylactically or therapeutically to reduce the severity of diseases associated with Hepatitis C virus, and for diagnosis and detection of HCV and HCV-associated diseases. Methods of using these compounds are also disclosed.

Abstract: Methods for modulating expression of a gene are provided. The methods comprise the steps of selecting a portion of an RNA coded by the gene, wherein the RNA is capable of interacting with a protein, preparing an oligonucleotide or oligonucleotide analog to mimic the portion of the RNA, and contacting cells containing the gene with the oligonucleotide or oligonucleotide analog. Methods of treating a disease are also provided. The methods comprise selecting a portion of an RNA coded by a gene whose expression is believed to be responsible for the disease, preparing an oligonucleotide or oligonucleotide analog to mimic the portion, and contacting an organism suspected of having the disease with the oligonucleotide or oligonucleotide analog.

Abstract: Oligonucleotides which selectively bind to target biomolecules are determined by in vitro assay of a pool of random oligonucleotides for activity against the biomolecules, followed by recovery and characterization of selected oligonucleotides. Oligonucleotides so determined may be utilized for therapeutic, diagnostic and research reagent purposes.

Abstract: Expression of genes may be modulated by employment of compositions which are capable of RNA mimicry. A portion of RNA coded by the gene whose expression is to be modulated is selected which is capable of interacting with one or more proteins. An oligonucleotide or oligonucleotide analog is then prepared in such a way as to mimic the portion of the RNA. Cells containing the gene are then contacted with the oligonucleotide or oligonucleotide analog to effect the modulation. Therapeutic compositions and methods, especially for the treatment of human immunodeficiency, are disclosed.

Abstract: Methods for modulating the expression of viral genes are provided by selecting a portion of RNA coded by the gene, said RNA portion having subportions forming a secondary structure, and contacting the RNA with oligonucleotide of 6 to 50 which can bind with at least one of said subportions of the RNA. In accordance with the preferred embodiments, oligonucleotides are designed to bind to RNA secondary structures which are of significance to the expression of the gene coding for said RNA. In accordance with a preferred embodiment, methods of treatment of human immunodeficiency virus are similarly disclosed wherein the oligonucleotides are targeted at the CAR or gag-pol region of HIV RNA.

Abstract: Expression of genes may be modulated by employment of compositions which are capable of RNA mimicry. A portion of RNA coded by the gene whose expression is to be modulated is selected which is capable of interacting with one or more proteins. An oligonucleotide or oligonucleotide analog is then prepared in such a way as to mimic the portion of the RNA. Cells containing the gene are then contacted with the oligonucleotide or oligonucleotide analog to effect the modulation. Therapeutic compositions and methods, especially for the treatment of human immunodeficiency, are disclosed.

Abstract: Methods useful for the determination of oligomers which have specific activity for a target molecule from a pool of primarily randomly assembled oligomers are provided. The disclosed methods involve repeated syntheses of increasingly simplified sets of oligomers coupled with selection procedures for determining oligomers having the highest activity. Freedom from the use of enzymes allows the application of these methods to any molecules which can be oligomerized in a controlled fashion.

Abstract: Oligonucleotides which selectively bind to target biomolecules are determined by in vitro assay of a pool of random oligonucleotides for activity against said biomolecules, followed by recovery and characterization of selected oligonucleotides. Oligonucleotides so determined may be utilized for therapeutic, diagnostic and research reagent purposes.

Abstract: Methods useful for the determination of oligomers which have specific activity for a target molecule from a pool of primarily randomly assembled subunits are provided. The disclosed methods involve repeated syntheses of increasingly simplified sets of oligomers coupled with selection procedures for determining oligomers having the highest activity. Freedom from the use of enzymes allows the application of these methods to any molecules which can be oligomerized in a controlled fashion.