1609 results about "RNA interference" patented technology

The present invention provides a polynucleotide that not only has a high RNA interference effect on its target gene, but also has a very small risk of causing RNA interference against a gene unrelated to the target gene. A sequence segment conforming to the following rules (a) to (d) is searched from the base sequences of a target gene for RNA interference and, based on the search results, a polynucleotide capable of causing RNAi is designed, synthesized, etc.:(a) The 3′ end base is adenine, thymine, or uracil,(b) The 5′ end base is guanine or cytosine,(c) A 7-base sequence from the 3′ end is rich in one or more types of bases selected from the group consisting of adenine, thymine, and uracil, and(d) The number of bases is within a range that allows RNA interference to occur without causing cytotoxicity.

The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

This invention relates to compounds, compositions, and methods useful for modulating BCL2 gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of BCL2 gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of BCL2 genes (e.g., BCL2, BCL-XL, BCL2-L1, MCL-1 CED-9, BAG-1, E1B-194 and / or BCL-A1). The small nucleic acid molecules are useful in the treatment of cancer, malignant blood disease, polycytemia vera, idiopathic myelofibrosis, essential thrombocythemia, myelodysplastic syndromes, autoimmune disease, viral infection, and proliferative diseases and conditions

This invention relates to compounds, compositions, and methods useful for modulating mitogen activated protein kinase (MAP kinase) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of MAP kinase gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of MAP kinase genes, such as Jun amino-terminal kinase (e.g., JNK-1, JNK-2), p38 (MAPK 14), ERK (e.g., ERK-1, ERK-2) and / or c-Jun.

This invention relates to compounds, compositions, and methods useful for modulating wingless (WNT) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of WNT gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of WNT genes such as WNT3A and WNT7A.

The present invention relates to targeted RNAi for the treatment of heart failure by modulating defective cardiac Ca2+ homeostasis via decreasing expression or activity of phospholamban (PLB) using adeno-associated virus (AAV) transfection of cardiomyocytes. Methods for decreasing ventricular arrhythmias, as well as methods for overall improvement of survival from heart failure in subjects are also disclosed. Further, the present invention provides methods which can be used to diagnose susceptibility to treatment by RNAi, and includes pharmaceutical compositions, kits and vectors including an RNAi sequence.

This invention relates to compounds, compositions, and methods useful for modulating tumor necrosis factor and / or tumor necrosis factor receptor gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of tumor necrosis factor and / or tumor necrosis factor receptor gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of tumor necrosis factor and / or tumor necrosis factor receptor genes, (TNF and / or TNF receptor).

The present invention concerns methods and nucleic acid based reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, veterinary, agricultural, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to multifunctional short interfering nucleic acid (multifunctional siNA) molecules that modulate the expression of one or more genes in a biologic system, such as a cell, tissue, or organism via RNA interference (RNAi). The bifunctional short interfering nucleic acid (multifunctional siNA) molecules of the invention can target more than one regions of nucleic acid sequence in a single target nucleic acid molecule or can target regions of nucleic acid sequence in differing target nucleic acid molecules. The self multifunctional siNA molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.

The present invention is directed membrane active poly(vinyl ester) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cells in vivo. RNAi polynucleotides are conjugated to the poly(vinyl ester) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(vinyl ester) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.

The invention concerns a method for the targeted selection of a double-stranded ribonucleic acid (dsRNA) consisting of two single strands that exhibits increased effectiveness in inhibiting the expression of a target gene by means of RNA interference, whereby the sequences of the single strands of the dsRNA are selected in such a way that on both ends of the dsRNA the last complementary nucleotide pair is a G-C, or at least two of the last four complementary nucleotide pairs are G-C pairs; whereby the dsRNA exhibits a single-stranded overhang consisting of 1 to 4 unpaired nucleotides at the first end, and no overhang at the second end; whereby the unpaired nucleotide of the single-stranded overhang that is directly adjacent to the last complementary nucleotide pair contains a purine base.

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.

This invention relates to compounds, compositions, and methods useful for modulating gene expression using short interfering nucleic acid (siNA) molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of genes, such as expressed pseudogenes associated with the maintenance or development of diseases, disorders, traits, and conditions in a subject or organism. The invention also provides small nucleic acid molecules with reduced or attenuated immunostimulatory properties and methods for designing and synthesizing such small nucleic acid molecules having improved toxicologic properties while retaining RNAi activity.

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cell in vivo. The pharmacokinetic modulator improve in vivo targeting compared to the targeting ligand alone. Targeting ligand-pharmacokinetic modulator targeting moiety targeted RNAi polynucleotides can be administered in vivo alone or together with co-targeted delivery polymers.

The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

Implantable medical device eluting drug locally and in prolonged period is provided, including several types of such a device, the treatment modes of implementation and methods of implantation. The device comprising of polymeric substrate, such as a matrix for example, that is used as the device body, and drugs, and in some cases additional scaffolding materials, such as metals or additional polymers, and materials to enhance visibility and imaging. The selection of drug is based on the advantageous of releasing drug locally and in prolonged period, where drug is released directly to the extracellular matrix (ECM) of the diseased area such as tumor, inflammation, degeneration or for symptomatic objectives, or to injured smooth muscle cells, or for prevention. One kind of drug is the gene silencing drugs based on RNA interference (RNAi), including but not limited to si RNA, sh RNA, or antisense RNA / DNA, ribozyme and nucleoside analogs. The modes of implantation in some embodiments are existing implantation procedures that are developed and used today for other treatments, including brachytherapy and needle biopsy. In such cases the dimensions of the new implant described in this invention are similar to the original implant. Typically a few devices are implanted during the same treatment procedure.

The invention concerns with the molecular biology, molecular genetics and biotechnology and can be used in the gene-therapy in the medicine and the agriculture or in the industrial biotechnology for a gene-specific silencing of the disease-related genes or the genes interfering a buildup of a product, respectively. The approach is suggested for changing of genetic properties of an organism by RNA interference leading to gene-specific silencing of a selected gene by RNA molecules, that are complementary in a parallel orientation (pcRNA) to mRNA of the selected gene; pcRNA are synthesized in vivo or in vitro on the artificial DNA sequence possessing symmetrical nucleotide ordering (mirror inversion) in respect to the nucleotide sequence of the gene. The invention suggests the general approach for changing of genetic properties of an organism and is based on the biological properties of mirror inversions of nucleotide sequences that are realized in RNA interference and gene-specific silencing.

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted melittin delivery peptides. Delivery peptides provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery peptides.

The present invention concerns methods and reagents useful in modulating Parkinson genes, for example, PARK1 (SNCA), PARK2, PARK7, and / or PARK5 gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against SNCA gene expression and / or activity. The small nucleic acid molecules are useful in the diagnosis and treatment of Parkinson Disease (PD), and any other disease or condition that responds to modulation of PARK1 (SNCA), PARK2, PARK7, and / or PARK5 expression or activity.

This invention relates to a method of modulating the expression of a target gene in an organism comprising administering an iRNA agent, wherein the iRNA comprises at least one 2′-deoxy-2′-fluoro (2′-F) nucleotide in the antisense strand and at least one modified nucleotide in the sense strand. The invention also relates to compositions comprising a single-stranded oligonucleotide that contains at least one 2′-deoxy-2′-fluoro (2′-F) nucleotide. siRNA molecule containing these oligonucleotides have decreased immunogenicity.

The present invention concerns compounds, compositions, and methods for the study, diagnosis, and treatment of diseases and conditions associated with alpha-1 antitrypsin (AAT) allelic variants that respond to the modulation of gene expression and / or activity. The present invention also concerns compounds, compositions, and methods relating to diseases and conditions associated with alpha-1 antitrypsin (AAT) allelic variants that respond to the modulation of expression and / or activity of genes involved in alpha-1 antitrypsin (AAT) gene expression pathways or other cellular processes that mediate the maintenance or development of alpha-1 antitrypsin (AAT) diseases and conditions such as liver disease, lung disease, and any other diseases or conditions that are related to or will respond to the levels of an alpha-1 antitrypsin (AAT) variant protein in a cell or tissue, alone or in combination with other therapies. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (mRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against the expression disease related genes or alleles having alpha-1 antitrypsin (AAT) sequences.

The present invention relates to agents, compositions and methods for inhibiting the expression of a target gene, comprising an RNAi agent bearing at least one galactosyl moiety. These are useful for delivering the gene expression inhibiting activity to cells, particularly hepatocytes, and more particularly in therapeutic applications.

The present invention is directed to small interfering RNA molecules targeted against a gene of interest in respiratory epithelial cells, and methods of using these RNA molecules.

The features of the present invention relate to compounds, compositions and methods useful for modulating the expression of vascular endothelial growth factor (VEGF), such as by the mechanism of RNA interference (RNAi). The compounds and compositions include iRNA agents that can be unmodified or chemically-modified.

The present invention provides methods and compositions for attenuating expression of a target gene in vivo. In general, the method includes administering RNAi constructs (such as small-interfering RNAs (i.e., siRNAs) that are targeted to particular mRNA sequences, or nucleic acid material that can produce siRNAs in a cell), in an amount sufficient to attenuate expression of a target gene by an RNA interference mechanism. In particular, the RNAi constructs may include one or more modifications to improve serum stability, cellular uptake and / or to avoid non-specific effect. In certain embodiments, the RNAi constructs contain an aptamer portion. The aptamer may bind to human serum albumin to improve serum half life. The aptamer may also bind to a cell surface protein that improves uptake of the construct.

Methods and compositions for performing RNA interference with decreased off-target effects are provided The methods and compositions permit effective and efficient applications of RNA interference to applications such as diagnostics and therapeutics through the use of modifications to the siRNA. Uniquely modified siRNAs have been developed that reduce off-target effects incurred in gene-silencing. The modifications comprise 2′-O-alkyl or mismatch modification(s) at specific positions on the sense and / or antisense strands.

It is intended to provide a double-stranded polynucleotide that is resistant to RNase and has RNA interference effect, etc. The present invention provides a double-stranded polynucleotide comprising sense and antisense strands comprising polynucleotides comprising a nucleotide unit of DNAs and 2′-O-methyl RNAs alternately combined.

The invention relates to the induction of apoptosis by inhibition of the sirtuin SIRT1 expression, in particular the induction of apoptosis in tumour cells. Materials and methods for inhibiting SIRT1 expression are provided, including RNA interference methods. In particular, the invention provides a method of treating a proliferative disease comprising administering to an individual in need thereof an effective amount of a SIRT1 inhibitor.