公开(公告)号：US07858769B2

公开(公告)日：2010-12-28

申请号：US10597755

申请日：2005-02-09

申请人： Vasant Jadhav ,  Shawn Zinnen

发明人： Vasant Jadhav ,  Shawn Zinnen

IPC分类号： C07H21/04

CPC分类号： C12N15/1131 ,  A61K38/00 ,  C12N15/1136 ,  C12N15/1138 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/3519 ,  C12N2310/51 ,  C12N2310/53

摘要： 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.

摘要翻译： 本发明涉及可用于调节各种应用中的基因表达的方法和基于核酸的试剂，包括在治疗，兽医，农业，诊断，靶标验证和基因组发现应用中的用途。 具体地，本发明涉及通过RNA干扰（RNAi）调节生物系统例如细胞，组织或生物体中的一种或多种基因的表达的多功能短干扰核酸（多功能siNA）分子。 本发明的双功能短干扰核酸（多功能siNA）分子可以靶向单个靶核酸分子中的多于一个核酸序列区域，或者靶向不同靶核酸分子中核酸序列的区域。 自身多功能siNA分子可用于治疗对细胞，组织或生物中基因表达或活性的调节作出反应的任何疾病或病症。

公开(公告)号：US20080050721A1

公开(公告)日：2008-02-28

申请号：US10568134

申请日：2004-08-17

申请人： Susan Radka ,  Zinnen Shawn ,  Vasant Jadhav ,  James McSwiggen ,  Narendra Vaish

发明人： Susan Radka ,  Zinnen Shawn ,  Vasant Jadhav ,  James McSwiggen ,  Narendra Vaish

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6813 ,  Y10T436/143333 ,  C12Q2545/114

摘要： The present invention concerns processes for the detection and quantitation of nucleic acid molecules, polynucleotides, and/or oligonucleotides in a sample using hybridizationdetection assays, antibody-mediated recognition assays, nucleic acid sensor molecules, chromatographic assays, and/or electrophoresis assays. The present invention specifically concerns processes for the detection and quantitation of double stranded nucleic acid molecules, polynucleotides, and/or oligonucleotides in a sample using hybridization-detection assays. The nucleic acid molecules, polynucleotides, and/or oligonucleotides can include molecules that mediate RNA interference, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules. The nucleic acid molecules, polynucleotides, and/or oligonucleotides can include nucleic acid aptamers, enzymatic nucleic acid molecules, decoys, antisense, 2,5′-oligoadenylate molecules, triplex forming oligonucleotides or any other nucleic acid molecule of interest. The present invention also concerns kits that allow for the detection and quantitation of nucleic acid molecules, polynucleotides, and/or oligonucleotides in a sample.

摘要翻译： 本发明涉及使用杂交检测测定，抗体介导的识别测定，核酸传感器分子，色谱测定和/或电泳测定来检测和定量样品中核酸分子，多核苷酸和/或寡核苷酸的方法。 本发明具体涉及使用杂交检测试验检测和定量样品中双链核酸分子，多核苷酸和/或寡核苷酸的方法。 核酸分子，多核苷酸和/或寡核苷酸可以包括介导RNA干扰的分子，例如短干扰核酸（siNA），短干扰RNA（siRNA），双链RNA（dsRNA），微RNA（miRNA） ，和短发夹RNA（shRNA）分子。 核酸分子，多核苷酸和/或寡核苷酸可以包括核酸适体，酶核酸分子，诱饵，反义，2,5'-寡腺苷酸分子，形成三链体的寡核苷酸或任何其它感兴趣的核酸分子。 本发明还涉及允许在样品中检测和定量核酸分子，多核苷酸和/或寡核苷酸的试剂盒。

公开(公告)号：US20070270579A1

公开(公告)日：2007-11-22

申请号：US11234730

申请日：2005-09-23

申请人： Vasant Jadhav ,  Narendra Vaish

发明人： Vasant Jadhav ,  Narendra Vaish

IPC分类号： C07H21/04

CPC分类号： C07H21/04

摘要： 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.

摘要翻译： 本发明涉及使用短干扰核酸（siNA）分子调节基因表达的化合物，组合物和方法。 特别地，本发明的特征在于小核酸分子，例如短干扰核酸（siNA），短干扰RNA（siRNA），双链RNA（dsRNA），微RNA（miRNA）和短发夹RNA（shRNA） ）分子和用于调节基因表达的方法，例如与受试者或生物中的疾病，病症，性状和病症的维持或发展相关的表达的假基因。 本发明还提供具有降低或减弱的免疫刺激性质的小核酸分子以及用于设计和合成具有改善的毒理学特性同时保留RNAi活性的这种小核酸分子的方法。

公开(公告)号：US20050209180A1

公开(公告)日：2005-09-22

申请号：US10942560

申请日：2004-09-15

申请人： Vasant Jadhav ,  Karl Kossen ,  Shawn Zinnen ,  Narendra Vaish ,  James McSwiggen

发明人： Vasant Jadhav ,  Karl Kossen ,  Shawn Zinnen ,  Narendra Vaish ,  James McSwiggen

IPC分类号： A61K48/00 ,  C07H21/02

摘要： This invention relates to compounds, compositions, and methods useful for modulating HCV 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 HCV 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 HCV genes.

摘要翻译： 本发明涉及使用短干扰核酸（siNA）分子调节HCV基因表达的化合物，组合物和方法。 本发明还涉及可用于通过使用小核酸分子调节参与通过RNA干扰（RNAi）的HCV基因表达和/或活性的途径的其它基因的表达和活性的化合物，组合物和方法。 特别地，本发明的特征在于小核酸分子，例如短干扰核酸（siNA），短干扰RNA（siRNA），双链RNA（dsRNA），微RNA（miRNA）和短发夹RNA（shRNA） ）分子和用于调节HCV基因表达的方法。

公开(公告)号：US10004814B2

公开(公告)日：2018-06-26

申请号：US15035950

申请日：2014-11-10

申请人： SIRNA THERAPEUTICS, INC. ,  Laura Sepp-Lorenzino ,  Vasant Jadhav ,  Duncan Brown

发明人： Marija Tadin-Strapps ,  Tayeba Khan ,  Walter Richard Strapps ,  Laura Sepp-Lorenzino ,  Vasant Jadhav ,  Duncan Brown

IPC分类号： C12N15/11 ,  A61K48/00 ,  A61K31/713 ,  C12N15/113 ,  A61K47/54

CPC分类号： A61K48/0058 ,  A61K31/713 ,  A61K47/543 ,  A61K47/554 ,  C12N15/1136 ,  C12N2310/14 ,  C12N2310/3515

摘要： The present invention provides methods comprising the in vivo delivery of small nucleic acid molecules capable of mediating RNA interference and reducing the expression of myostatin, wherein the small nucleic acid molecules are introduced to a subject by systemic administration. Specifically, the invention relates to methods comprising the in vivo delivery of short interfering nucleic acid (siNA) molecules that target a myostatin gene expressed by a subject, wherein the siNA molecule is conjugated to a lipophilic moiety, such as cholesterol. The myostatin siNA conjugates that are delivered as per the methods disclosed are useful to modulate the in vivo expression of myostatin, increase muscle mass and/or enhance muscle performance. Use of the disclosed methods is further indicated for treating musculoskeletal diseases or disorders and/or diseases or disorders that result in conditions in which muscle is adversely affected.

公开(公告)号：US20160256570A1

公开(公告)日：2016-09-08

申请号：US15035950

申请日：2014-11-10

申请人： Laura SEPP-LORENZINO ,  Vasant JADHAV ,  Duncan BROWN ,  SIRNA THERAPEUTICS, INC.

发明人： Marija Tadin-Strapps ,  Tayeba Khan ,  Walter Richard Strapps ,  Laura Sepp-Lorenzino ,  Vasant Jadhav ,  Duncan Brown

IPC分类号： A61K48/00 ,  C12N15/113 ,  A61K47/48

CPC分类号： A61K48/0058 ,  A61K31/713 ,  A61K47/543 ,  A61K47/554 ,  C12N15/1136 ,  C12N2310/14 ,  C12N2310/3515

摘要： The present invention provides methods comprising the in vivo delivery of small nucleic acid molecules capable of mediating RNA interference and reducing the expression of myostatin, wherein the small nucleic acid molecules are introduced to a subject by systemic administration. Specifically, the invention relates to methods comprising the in vivo delivery of short interfering nucleic acid (siNA) molecules that target a myostatin gene expressed by a subject, wherein the siNA molecule is conjugated to a lipophilic moiety, such as cholesterol. The myostatin siNA conjugates that are delivered as per the methods disclosed are useful to modulate the in vivo expression of myostatin, increase muscle mass and/or enhance muscle performance. Use of the disclosed methods is further indicated for treating musculoskeletal diseases or disorders and/or diseases or disorders that result in conditions in which muscle is adversely affected.

摘要翻译： 本发明提供了包括体内递送能够介导RNA干扰并降低肌生成抑制素表达的小核酸分子的方法，其中通过全身给药将小核酸分子引入受试者。 具体而言，本发明涉及包括体内递送针对受试者表达的肌生长抑制素基因的短干扰核酸（siNA）分子的方法，其中所述siNA分子与亲脂部分如胆固醇结合。 根据所公开的方法递送的肌生成抑制素siNA缀合物可用于调节肌生成抑制素的体内表达，增加肌肉质量和/或增强肌肉性能。 还公开了所公开的方法的使用用于治疗导致肌肉受到不利影响的病症的肌肉骨骼疾病或病症和/或疾病或病症。

公开(公告)号：US07517864B2

公开(公告)日：2009-04-14

申请号：US11299391

申请日：2005-12-09

申请人： Chandra Vargeese ,  Vasant Jadhav ,  David Morrissey

发明人： Chandra Vargeese ,  Vasant Jadhav ,  David Morrissey

IPC分类号： A61K48/00 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12N15/1138 ,  C12N15/1136 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/332 ,  C12N2320/32

摘要： This invention relates to compounds, compositions, and methods useful for modulating VEGF and/or VEGFR 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 VEGF and/or VEGFR 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 VEGF and/or VEGFR genes. The application also relates to methods of treating diseases and conditions associated with VEGF and/or VEGFR gene expression, such as ocular diseases and conditions, including age related macular degeneration (AMD) and diabetic retinopathy, as well as providing dosing regimens and treatment protocols.

摘要翻译： 本发明涉及使用短干扰核酸（siNA）分子调节VEGF和/或VEGFR基因表达的化合物，组合物和方法。 本发明还涉及使用小核酸分子调节参与VEGF和/或VEGFR基因表达和/或活性通过RNA干扰（RNAi）的其它基因的表达和活性的化合物，组合物和方法。 特别地，本发明的特征在于小核酸分子，例如短干扰核酸（siNA），短干扰RNA（siRNA），双链RNA（dsRNA），微RNA（miRNA）和短发夹RNA（shRNA） ）分子和用于调节VEGF和/或VEGFR基因表达的方法。 该应用还涉及治疗与VEGF和/或VEGFR基因表达相关的疾病和病症的方法，例如眼部疾病和病症，包括年龄相关性黄斑变性（AMD）和糖尿病性视网膜病变，以及提供给药方案和治疗方案。

公开(公告)号：US20080039412A1

公开(公告)日：2008-02-14

申请号：US10597755

申请日：2005-02-09

申请人： Vasant Jadhav ,  Shawn Zinnen

发明人： Vasant Jadhav ,  Shawn Zinnen

IPC分类号： A61K31/70 ,  A61P43/00 ,  C07H19/00

CPC分类号： C12N15/1131 ,  A61K38/00 ,  C12N15/1136 ,  C12N15/1138 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/3519 ,  C12N2310/51 ,  C12N2310/53

摘要： 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.

摘要翻译： 本发明涉及可用于调节各种应用中的基因表达的方法和基于核酸的试剂，包括在治疗，兽医，农业，诊断，靶标验证和基因组发现应用中的用途。 具体地，本发明涉及通过RNA干扰（RNAi）调节生物系统例如细胞，组织或生物体中的一种或多种基因的表达的多功能短干扰核酸（多功能siNA）分子。 本发明的双功能短干扰核酸（多功能siNA）分子可以靶向单个靶核酸分子中的多于一个核酸序列区域，或者靶向不同靶核酸分子中核酸序列的区域。 自身多功能siNA分子可用于治疗对细胞，组织或生物中基因表达或活性的调节作出反应的任何疾病或病症。

公开(公告)号：US20070173473A1

公开(公告)日：2007-07-26

申请号：US11487788

申请日：2006-07-17

申请人： James McSwiggen ,  Vasant Jadhav ,  Narendra Vaish ,  Roberto Guerciolini ,  Chandra Vargeese

发明人： James McSwiggen ,  Vasant Jadhav ,  Narendra Vaish ,  Roberto Guerciolini ,  Chandra Vargeese

IPC分类号： A61K48/00 ,  C07H21/02

CPC分类号： C12N15/1131 ,  C12N2310/14

摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to 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 capable of mediating RNA interference (RNAi) against Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, and others that can inhibit the function of endogenous RNA molecules, such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PCSK9 gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC), including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules and are useful, for example, in providing compositions to prevent, inhibit, or reduce metabolic diseases traits and conditions, including but not limited to hyperlipidemia, hypercholesterolemia, cardiovascular disease, atherosclerosis, hypertension, diabetis (e.g., type I and/or type II diabetis), insulin resistance, obesity and/or other disease states, conditions, or traits associated with PCSK9 gene expression or activity in a subject or organism.

公开(公告)号：US20070049543A1

公开(公告)日：2007-03-01

申请号：US11455205

申请日：2006-06-16

申请人： James McSwiggen ,  Chandra Vargeese ,  Vasant Jadhav

发明人： James McSwiggen ,  Chandra Vargeese ,  Vasant Jadhav

IPC分类号： A61K48/00 ,  C07H21/02

CPC分类号： C12N15/1137 ,  C12N15/1131 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/33 ,  C12N2310/52 ,  C12Y101/01146 ,  C12N2310/3521

摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of 11 beta-hydroxysteroid dehydrogenase-1 (11 beta-HSD-1) gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in 11 beta-hydroxysteroid dehydrogenase-1 (11 beta-HSD-1) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to 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 capable of mediating RNA interference (RNAi) against 11 beta-hydroxysteroid dehydrogenase-1 (11 beta-HSD-1) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, and others that can inhibit the function of endogenous RNA molecules, such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate 11 beta-HSD-1 gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC), including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules and are useful, for example, in providing compositions to prevent, inhibit, or reduce metabolic diseases traits and conditions, including but not limited to diabetis (e.g., type I and/or type II diabetis), insulin resistance, obesity, hypercholesterolemia, cardiovascular disease and/or other disease states, conditions, or traits associated with 11 beta-HSD-1 gene expression or activity in a subject or organism.