Abstract: The invention is directed to compositions and methods for selectively reducing the expression of a gene product from a desired target gene in a cell, as well as for treating diseases caused by the expression of the gene. More particularly, the invention is directed to compositions that contain double stranded RNA (“dsRNA”), and methods for preparing them, that are capable of reducing the expression of target genes in eukaryotic cells. The dsRNA has a first oligonucleotide sequence that is between 25 and about 30 nucleotides in length and a second oligonucleotide sequence that anneals to the first sequence under biological conditions. In addition, a region of one of the sequences of the dsRNA having a sequence length of at least 19 nucleotides is sufficiently complementary to a nucleotide sequence of the RNA produced from the target gene to trigger the destruction of the target RNA by the RNAi machinery.

Abstract: Double-stranded and single-stranded RNA molecules, and their use in methods for inducing interferon are provided. The interferon induction provides anti-viral and other medically useful effects, such as anti-cancer effects. Also provided are methods for reducing or inhibiting interferon induction exhibited by such molecules, particularly siRNA and shRNA molecules produced in vitro.

Abstract: In some embodiments, aptamers that specifically bind pancreatic cancer cells are provided. Such aptamers may include an RNA molecule that specifically binds a pancreatic cancer cell surface protein. In certain embodiments, the RNA molecule that is used as an aptamer may include a nucleotide sequence of GAAUGCCC (SEQ ID NO: 8). In other embodiments, the RNA molecule may include a nucleotide sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, or SEQ ID NO:6. In certain embodiments, the aptamer may be conjugated to one or more therapeutic agents (e.g., an shRNA molecule, an siRNA molecule, an mRNA molecule, or an miRNA molecule), one or more diagnostic agents, or a combination thereof. The aptamers and their conjugates may be used to deliver therapeutic agents to a pancreatic cancer cell, and/or in methods for treating or diagnosing pancreatic cancer.

Abstract: An aptamer-mRNA conjugate is provided. The aptamer-mRNA conjugate may include an aptamer component that binds a membrane associated protein on a target cell and an mRNA component that is expressed by the target cell.

Abstract: The invention provides compositions and methods for selectively reducing the expression of a gene product from a desired target gene, as well as treating diseases caused by expression of the gene. The method involves introducing into the environment of a cell an amount of a double-stranded RNA (dsRNA) such that a sufficient portion of the dsRNA can enter the cytoplasm of the cell to cause a reduction in the expression of the target gene. The dsRNA has a first oligonucleotide sequence that is between 26 and about 30 nucleotides in length and a second oligonucleotide sequence that anneals to the first sequence under biological conditions. In addition, a region of one of the sequences of the dsRNA having a sequence length of from about 19 to about 23 nucleotides is complementary to a nucleotide sequence of the RNA produced from the target gene.

Abstract: Provided herein are signal activatable molecular constructs for enzyme-assisted delivery of molecules and related components, such as a sensor domain, compositions, methods and systems.

Abstract: The present invention relates to compositions and methods for delivery of siRNA to specific cells or tissue. More particularly, the present invention relates to compositions and methods for cell type-specific delivery of anti-HIV siRNAs via fusion to an anti-gp120 aptamer.

Abstract: Universal RNA interference (RNAi) molecules having an inhibitory RNA sequence which binds a target pathologic RNA sequence are provided according to some embodiments. Such RNAi molecules bind the target pathologic RNA sequence via at least one non-Watson Crick paired base. In some embodiments, the target pathologic RNA sequence is a target viral RNA sequence derived from a human immunodeficiency HIV virus, a hepatitis B virus (HBV), a hepatitis C virus (HCV), or an influenza virus.

Abstract: Provided herein are signal activatable molecular constructs for enzyme-assisted delivery of molecules and related components, such as a sensor domain, compositions, methods and systems.

Abstract: The present invention relates to methods and compositions for the treatment of diseases, including cancer, infectious diseases and autoimmune diseases. The present invention also relates to methods and compositions for improving immune function. More particularly, the present invention relates to multifunctional molecules that are capable of being delivered to cells of interest for the treatment of diseases and for the improvement in immune function.

Abstract: The present invention relates to methods and compositions for the treatment of diseases, including cancer, infectious diseases and autoimmune diseases. The present invention also relates to methods and compositions for improving immune function. More particularly, the present invention relates to multifunctional molecules that are capable of being delivered to cells of interest for the treatment of diseases and for the improvement in immune function.

Abstract: Methods for producing interfering RNA molecules in mammalian cells are provided. Therapeutic uses for the expressed molecules, including inhibiting expression of HIV, are also provided.

Abstract: Provided herein are signal activatable molecular constructs for delivery of molecules and related components, compositions, methods, and systems, having a 17 to 30 by targeting domain duplex RNA, at least one protection strand having a protection segment and linker segment and a sensor strand having a displacement segment and a toehold segment, in which in an inactive conformation the protection segment and the displacement segment form a sensor domain duplex polynucleotide covalently attached to the targeting domain and presenting the toehold segment for binding to a signal molecule. In an active conformation the sensor strand is bound to the signal molecule and is detached from the at least one protection strand and from the targeting domain; and the targeting domain attaches the at least one protection strand in a configuration allowing processing by Dicer and/or an Argonaute enzyme.

Abstract: The present invention relates to compositions and methods for delivery of siRNA to specific cells or tissue. More particularly, the present invention relates to compositions and methods for cell type-specific delivery of anti-HIV siRNAs via fusion to an anti-gp120 aptamer.

Abstract: Amplification-based methods and kits for rapidly producing siRNA expression cassettes are provided. Also provided are methods for expressing amplified siRNA expression cassettes in cells.

Abstract: Provided herein are exonuclease resistant polynucleotides and related constructs, compositions, methods and systems.

Abstract: In some embodiments, aptamers that specifically bind pancreatic cancer cells are provided. Such aptamers may include an RNA molecule that specifically binds a pancreatic cancer cell surface protein. In certain embodiments, the RNA molecule that is used as an aptamer may include a nucleotide sequence of GAAUGCCC (SEQ ID NO: 8). In other embodiments, the RNA molecule may include a nucleotide sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, or SEQ ID NO:6. In certain embodiments, the aptamer may be conjugated to one or more therapeutic agents (e.g., an shRNA molecule, an siRNA molecule, an mRNA molecule, or an miRNA molecule), one or more diagnostic agents, or a combination thereof. The aptamers and their conjugates may be used to deliver therapeutic agents to a pancreatic cancer cell, and/or in methods for treating or diagnosing pancreatic cancer.

Abstract: An aptamer-mRNA conjugate is provided. The aptamer-mRNA conjugate may include an aptamer component that binds a membrane associated protein on a target cell and an mRNA component that is expressed by the target cell.

Abstract: Methods for producing interfering RNA molecules in mammalian cells are provided. Therapeutic uses for the expressed molecules, including inhibiting expression of HIV, are also provided.

Abstract: The invention is directed to compositions and methods for selectively reducing the expression of a gene product from a desired target gene in a cell, as well as for treating diseases caused by the expression of the gene. More particularly, the invention is directed to compositions that contain double stranded RNA (“dsRNA”), and methods for preparing them, that are capable of reducing the expression of target genes in eukaryotic cells. The dsRNA has a first oligonucleotide sequence that is between 25 and about 30 nucleotides in length and a second oligonucleotide sequence that anneals to the first sequence under biological conditions. In addition, a region of one of the sequences of the dsRNA having a sequence length of at least 19 nucleotides is sufficiently complementary to a nucleotide sequence of the RNA produced from the target gene to trigger the destruction of the target RNA by the RNAi machinery.