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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.

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).

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 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.

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.

This invention relates to compounds, compositions, and methods useful for modulating interleukin and / or interleukin 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 interleukin and / or interleukin 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 (mRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of interleukin and / or interleukin receptor genes such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, and IL-27 genes and IL-IR, IL-2R, IL-3R, IL-4R, IL-5R, IL-6R, IL-7R, IL-8R, IL-9R, IL-10R, IL-11R, IL-12R, IL-13R, IL-14R, IL-15R, IL-16R, IL-17R, IL-18R, IL-19R, IL-20R, IL-21R, IL-22R, IL-23R, IL-24R, IL-25R, IL-26R, and IL-27R genes.

The present invention concerns methods and reagents useful in modulating vascular endothelial growth factor (VEGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D) and / or vascular endothelial growth factor receptor (e.g., VEGFR1, VEGFR2 and / or VEGFr3) 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 VEGF and / or VEGFr gene expression and / or activity. The small nucleic acid molecules are useful in the diagnosis and treatment of cancer, proliferative diseases, and any other disease or condition that responds to modulation of VEGF and / or VEGFr expression or activity.

This invention relates to compounds, compositions, and methods useful for modulating Connexin 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 Connexin 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 (siNA), double-stranded RNA (dsRNA), micro-RNA (mRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of Connexin genes such as Connexin43 (Cx43).

This invention relates to compounds, compositions, and methods useful for modulating gene expression using chemically modified double stranded nucleic acid molecules. In particular, the instant invention features double stranded nucleic acid molecules including 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 via RNA interference (RNAi). The invention features various modifications to double stranded nucleic acid structures, including chemically modified overhangs and optimized stabilization motifs of guide (antisense) strand and passenger (sense) strands of double stranded nucleic acid molecules that allow for potent RNA interference in therapeutically relevant applications.

This invention relates to compounds, compositions, and methods useful for modulating epidermal growth factor receptor (EGFR) (e.g., HER1, HER2, HER3, and / or HER4) 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 EGFR 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 (mRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of EGFR genes, including HER 1, HER2, HER3, and / or HER4. The small nucleic acid molecules are useful in the treatment and diagnosis of cancer.

This invention relates to compounds, compositions, and methods useful for modulating hairless (HR) 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 hairless 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 hairless (HR) genes.

This invention relates to compounds, compositions, and methods useful for modulating transforming growth factor beta (TGF-beta) and / or transforming growth factor beta receptor (TGF-betaR) 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 TGF-beta and / or TGF-betaR 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 TGF-beta and / or TGF-betaR genes.

This invention relates to compounds, compositions, and methods useful for modulating STAT3 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 STAT3 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 (mRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of STAT3 genes. Such small nucleic acid molecules are useful, for example, for treating, preventing, inhibiting, or reducing cancer, proliferative, and / or inflammatory diseases, disorders, or conditions in a subject or organism, such as psoriasis, eczema, dermatitis, Crohn's disease, and inflammatory bowel disease, and for any other disease, trait, or condition that is related to or will respond to the levels of STAT3 in a cell or tissue, alone or in combination with other treatments or therapies.

This invention relates to compounds, compositions, and methods useful for modulating myostatin (GDF8) 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 myostatin 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 myostatin genes.

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 present invention related to fluoroalkoxy (“—OCF3”) nucleosides, nucleotides, and polynucleotides comprising fluoroalkoxy nucleotides. The present invention also relates to methods of synthesizing fluoroalkoxy nucleosides, nucleotides, and polynucleotides comprising fluoroalkoxy nucleotides. The present invention also relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and / or activity. The invention also relates to fluoroalkoxy modified nucleic acid molecules, such as ribozymes, antisense, aptamers, decoys, triplex forming oligonucleotides (TFO), immune stimulatory oligonucleotides (ISO), immune modulatory oligonucleotides (IMO), and small nucleic acid molecules, including 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 polynucloetide targets. Such small nucleic acid molecules are useful, for example, in providing compositions to treat, prevent, inhibit, or reduce diseases, traits, or conditions in a subject or organism.

This invention relates to compounds, compositions, and methods useful for modulating TGF-beta and / or TGF-betaR 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 TGF-beta and / or TGF-betaR 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 TGF-beta and / or TGF-betaR genes. Such small nucleic acid molecules are useful, for example, for treating, preventing, inhibiting, or reducing inflammatory, respiratory, autoimmune, and / or proliferative diseases, disorders, conditions, or traits in a cell, subject or organism and any other disease, condition, trait or indication that can respond to the level of TGF-beta and / or TGF-betaR in a cell or tissue; or alternately in providing long term hematopeitic reconstitution in a subject or organism.

This invention relates to compounds, compositions, and methods useful for modulating hypoxia inducible factor (e.g., HIF1) 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 HIF1 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 HIF1 genes.

This invention relates to compounds, compositions, and methods useful for modulating Angiopoietin 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 Angiopoietin 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 (mRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of Angiopoietin genes, such as Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Angiopoietin-3 (Ang-3), and Angiopoietin-4 (Ang-4).

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.

This invention relates to compounds, compositions, and methods useful for modulating interleukin and / or interleukin 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 interleukin and / or interleukin 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 (mRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of interleukin and / or interleukin receptor genes, such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, and IL-27 genes and IL- 1 R, IL-2R, IL-3R, IL-4R, IL-5R, IL-6R, IL-7R, IL-8R, IL-9R, IL-10R, IL-11R, IL-12R, IL-13R, IL-14R, IL- 15 R, IL-16R, IL-17R, IL-18R, IL-19R, IL-20R, IL-21R, IL-22R, IL-23R, IL-24R, IL-25R, IL-26R, and IL-27R. Such small nucleic acid molecules are useful, for example, for treating, preventing, inhibiting, or reducing cancer, inflammatory, respiratory, autoimmune, cardiovascular, neurological, and / or proliferative diseases, disorders, or conditions in a subject or organism, and for any other disease, trait, or condition that is related to or will respond to the levels of interleukin and / or interleukin receptor in a cell or tissue, alone or in combination with other treatments or therapies.

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.

This invention relates to compounds, compositions, and methods useful for modulating intercellular adhesion molecule (ICAM) 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 ICAM 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 ICAM genes.

This invention relates to compounds, compositions, and methods useful for modulating chemokine receptor (CXCR) 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 CXCR 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 CXCR genes such as CXCR4 and CXCR7A.

This invention relates to compounds, compositions, and methods useful for modulating Myc and / or Myb 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 Myc and / or Myb 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 Myc and / or Myb (e.g., c-Myc, N-Myc, L-Myc, c-Myb, a-Myb, b-Myb, and v-Myb) genes. The small nucleic acid molecules are useful in the treatment of cancer and other diseases and disorders.

This invention relates to compounds, compositions, and methods useful for modulating Stearoyl-CoA desaturase (SCD) 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 Stearoyl-CoA desaturase (SCD) 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 Stearoyl-CoA desaturase (SCD) genes.

This invention relates to compounds, compositions, and methods useful for modulating 5-alpha reductase (SRD5A-1, SRD5A-2) and androgen receptor (AR) 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 5-alpha reductase and androgen receptor (AR) 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 (mRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of 5-alpha reductase and androgen receptor (AR) genes.