Nucleic Acid Expression Inhibitors Patents (Class 536/24.5)
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Publication number: 20150104870Abstract: The present invention provides an agent for promoting neuronal differentiation of neural stem cells, which contains a p38 inhibitor. In addition, the present invention provides a method of promoting neuronal differentiation of neural stem cells, which includes cultivating neural stem cells in the presence of a p38 inhibitor. Neural stem cells are gliogenic or neurogenic. The p38 inhibitor is a nucleic acid which hybridizes to DNA or mRNA encoding p38 under physiological conditions, thereby inhibiting the transcription and/or translation thereof, an expression vector of the nucleic acid, a low molecular p38 inhibitor and the like.Type: ApplicationFiled: April 26, 2013Publication date: April 16, 2015Inventors: Hayato Kaneda, Hideyuki Okano, Takuya Shimazaki
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Publication number: 20150105443Abstract: The invention provides a single-stranded nucleic acid capable of inhibiting expression of a target gene having a delivery function. The nucleic acid contains, from the 5?-side to the 3?-side, a 5?-side region (Xc), a linker region (Lx), an inner region (Z), a linker region (Ly) and a 3?-side region (Yc) in this order, wherein the inner region (Z) is constituted by linkage of the inner 5?-side region (X) and the inner 3?-side region (Y), the 5?-side region (Xc) is complementary to the inner 5?-side region (X), the 3?-side region (Yc) is complementary to the inner 3?-side region (Y), at least one of the inner region (Z), the 5?-side region (Xc) and the 3?-side region (Yc) comprises an expression inhibitory sequence that inhibits expression of a target gene, and at least one of the 5?-terminus, the 3?-terminus, the linker region (Lx) and the linker region (Ly) is bound to a bio-related substance.Type: ApplicationFiled: May 25, 2013Publication date: April 16, 2015Inventors: Tadaaki Ohgi, Eriko Aoki, Chisato Emura, Tomohiro Hamasaki
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Publication number: 20150104440Abstract: The current disclosure reveals a complex regulatory pattern between miR-31 and AR, indicating that miR-31 plays a key role in prostate cancer development and progression. Another aspect of the current disclosure shows that miR-31 directly targets and destabilizes AR mRNA through interaction with the AR mRNA coding sequence showing that miR-31, or a fragment thereof has the ability to act as a novel therapeutic agent in treating cancer. The current disclosure also shows that AR indirectly represses miR-31 expression by binding to the miR-31 promoter region and modulating methyltransferase activity. Another aspect of the current disclosure shows that miR-31 indirectly modulates AR activity by modulating regulators of cell cycle progression. The disclosure further provides an isolated nucleic acid that modulates the activity of the androgen receptor in a cell.Type: ApplicationFiled: April 12, 2013Publication date: April 16, 2015Applicant: CORNELL UNIVERSITYInventors: Pei-Chun Lin, Mark A. Rubin
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Publication number: 20150105440Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of apolipoprotein B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding apolipoprotein B. Methods of using these compounds for modulation of apolipoprotein B expression and for treatment of diseases associated with expression of apolipoprotein B are provided.Type: ApplicationFiled: May 23, 2014Publication date: April 16, 2015Applicant: Genzyme CorporationInventors: Rosanne M. CROOKE, Mark J. GRAHAM
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Publication number: 20150105450Abstract: The present invention relates to novel short interfering RNA (siRNA) molecules that are multi-targeted. More specifically, the present invention relates to siRNA molecules that target two or more sequences. In one embodiment, multi-targeting siRNA molecules are designed to incorporate features of siRNA molecules and features of micro-RNA (miRNA) molecules. In another embodiment, multi-targeting siRNA molecules are designed so that each strand is directed to separate targets.Type: ApplicationFiled: December 22, 2014Publication date: April 16, 2015Applicant: CITY OF HOPEInventors: John J. ROSSI, Ola SNOVE, JR., Ali EHSANI, Pal SAETROM, JR., Britta HOEHN, Jane ZHANG, Lars AAGAARD
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Publication number: 20150105544Abstract: The present invention relates to the specific silencing of the ? (alpha), ? (beta), ? (gamma) and ? (omega)-gliadins of hard wheat for flour by RNA interference (RNAi) through employment of a polynucleotide which is transcribed into an hpRNA (hairpin RNA). Furthermore the present invention additionally relates to a vector, cell, plant or seed comprising the polynucleotide, the expression whereof is specifically directed in particular tissues of wheat seeds through gene expression-regulating sequences such as, for example, the promoter of a gene of ?-gliadins or the promoter of the gene encoding for a D-hordein.Type: ApplicationFiled: September 18, 2014Publication date: April 16, 2015Inventors: Francisco Barro Losada, Fernando Pistón Pistón, Javier Gil Humanes, Antonio Martin Muñoz
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Publication number: 20150105442Abstract: Provided is a novel molecule that inhibits the expression of the periostin gene. Also provided are methods of inhibiting the expression of the periostin gene or treating an eye disease using the same.Type: ApplicationFiled: March 29, 2013Publication date: April 16, 2015Applicants: AQUA Therapeutics Co., Ltd., KYUSHU UNIVERSITY NATIONAL UNIVERSITY CORPORATIONInventors: Shigeo Yoshida, Tomohiro Hamasaki, Keijiro Ishikawa, Takayuki Mizutani, Tatsuro Ishibashi, Tadaaki Ohgi, Takahito Nakama
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Publication number: 20150105445Abstract: 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.Type: ApplicationFiled: August 13, 2014Publication date: April 16, 2015Applicant: SIRNA THERAPEUTICS, INC.Inventors: James McSwiggen, Bharat Chowrira, Leonid Beigelman, Dennis Macejak, Shawn Zinnen, Pamela Pavco, Peter Haeberli, David Morrissey, Kathy Fosnaugh, Sharon F. Jamison, Nassim Usman, James Thompson, Chandra Vargeese, Weimin Wang, Tongqian Chen, Narendra K. Vaish
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Patent number: 9006418Abstract: The invention relates to antisense oligonucleotidic sequences (ODN) against Smad7 suitably modified, and their uses in medical field as therapeutic biological agents, in particular in the treatment of chronic inflammatory bowel disease, such as Crohn's disease and ulcerative colitis.Type: GrantFiled: December 30, 2013Date of Patent: April 14, 2015Assignee: Nogra Pharma LimitedInventor: Giovanni Monteleone
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Patent number: 9006200Abstract: The invention relates to microRNA mimics, corresponding to the miR-15/107 family, and to methodology for using microRNA mimics to treat malignant pleural mesothelioma (MPM) by restoring regulation of the expression of target genes of the miR-15/107 family in MPM tumor cells.Type: GrantFiled: March 13, 2013Date of Patent: April 14, 2015Assignee: Asbestos Diseases Research FoundationInventors: Glen Reid, Nico van Zandwijk
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Patent number: 9006206Abstract: Described herein are compositions and methods for modulation of p53-dependent cell death and cell proliferation. The compositions are microRNAs and associated nucleic acids.Type: GrantFiled: May 19, 2014Date of Patent: April 14, 2015Assignees: Rosetta Genomics Ltd., Yeda Research and Development Company Ltd.Inventors: Moshe Oren, Nina Raver-Shapira, Efi Marciano, Yael Spector
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Patent number: 9006414Abstract: Anti-sense-oriented RNA gene suppression agents in the form of a loop of anti-sense-oriented RNA is produced in cells of transgenic organisms, e.g. plants, by transcription from a recombinant DNA construct which comprises in 5? to 3? order a promoter element operably linked to an anti-sense-oriented DNA element and a complementary DNA element.Type: GrantFiled: December 20, 2010Date of Patent: April 14, 2015Assignee: Monsanto Technology LLCInventors: Shihshieh Huang, Thomas M. Malvar, Michael H. Luethy
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Patent number: 9006205Abstract: Alzheimer's disease (AD) is the most common human neurodegenerative disease of the CNS resulting in progressive neuronal death and memory loss. Despite intense investigations, no effective therapy is available to stop its onset or halt its progression. It was discovered that antisense oligonucleotide against neutral sphingomyelinase and GW4869, a chemical inhibitor of neutral sphingomyelinase, inhibit activation of glial cells and protect neurons in AD cell culture and animal models. These results suggest the following new treatment options for AD patients: Antisense oligonucleotide against neutral sphingomyelinase and GW4869.Type: GrantFiled: May 21, 2012Date of Patent: April 14, 2015Assignee: Rush University Medical CenterInventor: Kalipada Pahan
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Patent number: 9006417Abstract: The present invention provides novel, stable lipid particles having a non-lamellar structure and comprising one or more active agents or therapeutic agents, methods of making such lipid particles, and methods of delivering and/or administering such lipid particles. More particularly, the present invention provides stable nucleic acid-lipid particles (SNALP) that have a non-lamellar structure and that comprise a nucleic acid (such as one or more interfering RNA), methods of making the SNALP, and methods of delivering and/or administering the SNALP.Type: GrantFiled: June 30, 2011Date of Patent: April 14, 2015Assignee: Protiva Biotherapeutics, Inc.Inventors: Ed Yaworski, Lloyd B. Jeffs, Lorne R. Palmer
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Patent number: 9006199Abstract: Treatment of prostate cancer by regional and prolonged release of one or more nucleotide-based RNAi agents is provided.Type: GrantFiled: November 14, 2012Date of Patent: April 14, 2015Assignee: Silenseed Ltd.Inventors: Amotz Shemi, Elina Zorde Khvalevsky, Rachel Malka Gabai
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Patent number: 9006415Abstract: Aspects of the invention provide compositions and methods for delivering nucleic acids to target cells.Type: GrantFiled: April 6, 2011Date of Patent: April 14, 2015Assignee: Massachusetts Institute of TechnologyInventors: Yin Ren, Sangeeta N. Bhatia
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Patent number: 9006191Abstract: The present invention provides compositions comprising interfering RNA (e.g., siRNA, aiRNA, miRNA) that target polo-like kinase 1 (PLK-1) expression and methods of using such compositions to silence PLK-1 expression. More particularly, the present invention provides unmodified and chemically modified interfering RNA molecules which silence PLK-1 expression and methods of use thereof. The present invention also provides serum-stable nucleic acid-lipid particles (e.g., SNALP) comprising an interfering RNA molecule described herein, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. The present invention further provides methods of silencing PLK-1 gene expression by administering an interfering RNA molecule described herein to a mammalian subject. The present invention additionally provides methods of identifying and/or modifying PLK-1 interfering RNA having immunostimulatory properties.Type: GrantFiled: December 23, 2008Date of Patent: April 14, 2015Assignee: Protiva Biotherapeutics, Inc.Inventors: Ian MacLachlan, Adam Judge
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Patent number: 9006192Abstract: Described herein are methods and compositions for stimulating proliferation of cells that express adherent junctions and cease proliferation, for example, human corneal endothelial cells, by downregulation of certain cell-cell junctions. In one embodiment, downregulation is achieved using RNA interference, and contacting the cells with mitogenic growth factors and an agent that elevates intracytoplasmic cAMP. Furthermore, described herein are methods of isolating human corneal endothelial cells from keratocytes, and methods of preserving and maintaining viability of human corneal endothelial cell aggregates. Also described are surgical grafts comprising human corneal endothelial cells that have been isolated, optionally stored, and transiently contacted with an agent that downregulates expression of p 120, and a biocompatible support.Type: GrantFiled: September 27, 2007Date of Patent: April 14, 2015Assignee: TissueTech, Inc.Inventors: Scheffer Tseng, Wei Li, Yingting Zhu
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Patent number: 9006416Abstract: In one embodiment, a B cell specific aptamer-siRNA chimera is provided. The B cell specific aptamer-siRNa chimera may include an RNA aptamer that binds BAFF-R and an siRNA molecule conjugated to the RNA aptamer via a nucleotide linker. In another embodiment, a B cell specific RNA aptamer is provided. The RNA aptamer may be a molecule that binds to BAFF-R that has the sequence SEQ ID NO:37, SEQ ID NO:38 or SEQ ID NO:39. In some embodiments, the RNA aptamer is conjugated, via a nucleotide linker, to an siRNA molecule that suppresses expression of one or more target oncogenes in one or more B cells. In one aspect, the one or more target oncogenes are selected from Bcl6, Bcl2, STAT3, Cyclin D1, Cyclin E2 and c-myc. In another embodiment, methods for treating a B cell malignancy in a cancer patient are provided. Such methods may include administering a therapeutically effective amount of a therapeutic composition, the therapeutic composition comprising a B cell specific RNA aptamer that binds BAFF-R.Type: GrantFiled: October 12, 2012Date of Patent: April 14, 2015Assignee: City of HopeInventors: John Rossi, Katrin Tiemann, Jiehua Zhou, Britta Vallazza
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Patent number: 9006202Abstract: A method for treating latent HIV infection is disclosed. The method includes administering to a subject in need of such treatment an effective amount of an anti-I?B? agent, an anti-I?B? agent or both; and administering to the subject an effective amount of an antiviral agent. A pharmaceutical composition for treating latent HIV infection is also disclosed.Type: GrantFiled: June 27, 2013Date of Patent: April 14, 2015Assignee: Children's Research Institute, Children's National Medical CenterInventors: Steven L. Zeichner, Guerau Fernandez
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Publication number: 20150099794Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a G-alpha q subunit (GNAQ) of a heterotrimeric G gene, and methods of using the dsRNA to inhibit expression of GNAQ.Type: ApplicationFiled: October 6, 2014Publication date: April 9, 2015Inventors: Jared Gollob, Gregory Hinkle, Ivanka Toudjarska, David Bumcrot
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Publication number: 20150098938Abstract: Compositions of modulators of acyl-CoA lysocardiolipin acyf transferase 1 (ALCAT1) expression, function or activity are provided. In particular, inhibitors of ALCAT1 are useful in treating metabolic diseases, cardiac diseases and, in general diseases associated with mitochondrial dysfunction. Assays for identification of novel ALCAT1 modulators are provided.Type: ApplicationFiled: February 15, 2013Publication date: April 9, 2015Applicant: The Penn State Research FoundationInventor: Yuguang Shi
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Publication number: 20150099792Abstract: Provided herein are methods, compounds, and compositions for reducing expression of GCGR mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof.Type: ApplicationFiled: September 12, 2014Publication date: April 9, 2015Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Susan M. Freier, Sanjay Bhanot
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Publication number: 20150099795Abstract: A therapeutic agent for treating a Trypanosoma-associated disease; a method of preventing infection by Trypanosoma parasites, or killing Trypanosoma parasites; and use thereof, the therapeutic agent and the method each using a mechanism different from a mechanism used in conventional technology. The therapeutic agent of the present invention for treating a Trypanosoma-associated disease includes, as a medicinal component, an antisense oligonucleotide suppressing the expression of an inositol 1,4,5-trisphosphate receptor protein of Trypanosoma parasites.Type: ApplicationFiled: October 8, 2014Publication date: April 9, 2015Inventors: Katsuhiko Mikoshiba, Takeshi Nara, Muneaki Hashimoto
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Publication number: 20150099796Abstract: Compositions and methods for modulating the expression of a protein of interest are provided.Type: ApplicationFiled: October 31, 2014Publication date: April 9, 2015Inventors: Samuel Ian Gunderson, Rafal Goraczniak
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Patent number: 8999672Abstract: Improvements in plasmid DNA production technology are needed to insure the economic feasibility of future DNA vaccines and DNA therapeutics. General methods are described, by means of which it is possible to dramatically increase plasmid DNA productivity. These processes feature RNA based inducers of plasmid copy number.Type: GrantFiled: January 27, 2006Date of Patent: April 7, 2015Inventor: James A. Williams
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Patent number: 9000142Abstract: There is disclosed a photocleavable sense-antisense nucleobase polymer complex capable of modulating gene expression comprising an unnatural antisense nucleobase polymer that targets an mRNA, and a photocleavable sense nucleobase polymer noncovalently bound to the antisense nucleobase polymer, wherein the photocleavable sense nucleobase polymer comprises a plurality of nucleobase polymers connected by a photocleavable linkage. There is also disclosed a method for controlling the time and spatial position of gene expression comprising selecting a target mRNA, introducing the photocleavable sense-antisense nucleobase polymer complex into a cell, and selectively irradiating the cell with light.Type: GrantFiled: June 23, 2009Date of Patent: April 7, 2015Assignee: Syntrix Biosystems, Inc.Inventor: John A. Zebala
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Patent number: 8999947Abstract: Materials and methods for regulating gene expression using nanoparticles functionalized with antisense oligonucleotides are provided.Type: GrantFiled: August 20, 2012Date of Patent: April 7, 2015Assignee: Northwestern UniversityInventors: Chad A. Mirkin, Nathaniel L. Rosi, C. Shad Thaxton, David A. Giljohann
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Patent number: 9000264Abstract: The present invention provides molecular constructs and methods for use thereof, including constructs including heterologous miRNA recognition sites, constructs for gene suppression including a gene suppression element embedded within an intron flanked on one or on both sides by non-protein-coding sequence, constructs containing engineered miRNA or miRNA precursors, and constructs for suppression of production of mature microRNA in a cell. Also provided are transgenic plant cells, plants, and seeds containing such constructs, and methods for their use. The invention further provides transgenic plant cells, plants, and seeds containing recombinant DNA for the ligand-controlled expression of a target sequence, which may be endogenous or exogenous. Also disclosed are novel miRNAs and miRNA precursors from crop plants including maize and soy.Type: GrantFiled: July 8, 2010Date of Patent: April 7, 2015Assignee: Monsanto Technology LLCInventors: Edwards M. Allen, Larry A. Gilbertson, Nancy M. Houmard, Shihshieh Huang, Elysia K. Krieger, Thomas M. Malvar
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Patent number: 8999944Abstract: The present invention relates to screening assays for the identification of agents that can modify the interaction of thioredoxin interacting protein (TXNEP) on thioredoxin (TRX)5 preferably by inhibiting TXNIP downregulation of TXR. The use of such compounds, including the disclosed siRNA and antibodies against TXNIP, is contemplated for therapeutic or prophylactic treatment of vascular disease conditions, particularly those associated with pro-inflammatory activity of the TNF-ASK1-JNK-p38 pathways.Type: GrantFiled: January 20, 2006Date of Patent: April 7, 2015Assignee: University of RochesterInventor: Bradford C. Berk
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Patent number: 8999950Abstract: The present invention provides compositions comprising therapeutic nucleic acids such as interfering RNA (e.g., dsRNA such as siRNA) that target aldehyde dehydrogenase (ALDH) gene expression, lipid particles comprising one or more (e.g., a cocktail) of the therapeutic nucleic acids, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles (e.g., for treating alcoholism in humans).Type: GrantFiled: October 4, 2012Date of Patent: April 7, 2015Assignee: Protiva Biotherapeutics Inc.Inventors: Ian MacLachlan, Amy C. H. Lee
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Patent number: 9000144Abstract: In Caenorhabditis elegans, lin-4 and let-7 encode 22- and 21-nucleotide RNAs, respectively, that function as key regulators of developmental timing. Because the appearance of these short RNAs is regulated during development, they are also referred to as “small temporal RNAs” (stRNAs). We show that many more 21- and 22-nt expressed RNAs, termed microRNAs, (miRNAs), exist in invertebrates and vertebrates, and that some of these novel RNAs, similar to let-7 stRAN, are also highly conserved. This suggests that sequence-specific post-transcriptional regulatory mechanisms mediated by small RNAs are more general than previously appreciated.Type: GrantFiled: May 16, 2012Date of Patent: April 7, 2015Assignee: Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.Inventors: Thomas Tuschl, Mariana Lagos-Quintana, Winfried Lendeckel, Jutta Dammann, Reinhard Rauhut
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Patent number: 9000143Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the IKK-B gene, comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the IKK-B gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression or activation of the IKK-B gene using the pharmaceutical composition; and methods for inhibiting the expression of the IKK-B gene in a cell.Type: GrantFiled: December 30, 2010Date of Patent: April 7, 2015Assignee: Alnylam Pharmaceuticals, Inc.Inventors: Antonin de Fougerolles, Andrew Sprague, Jens Harborth, Maria Gabriela Belvisi, Mark Andrew Birrell, Elizabeth Louise Hardaker, Matthew Copeland Catley
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Patent number: 9000145Abstract: Disclosed are dsRNA constructs and methods to control insects via double stranded RNA interference of insect PBAN receptor genes.Type: GrantFiled: September 28, 2012Date of Patent: April 7, 2015Assignee: The United States of America, as represented by the Secretary of AgricultureInventors: Robert K. Vander Meer, Man Yeon Choi
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Publication number: 20150094461Abstract: Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.Type: ApplicationFiled: December 15, 2014Publication date: April 2, 2015Inventors: C. Frank Bennett, Susan M. Freier, Richard H. Griffey
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Publication number: 20150094358Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Hepatocyte Growth Factor (HGF), in particular, by targeting natural antisense polynucleotides of Hepatocyte Growth Factor (HGF). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of HGF.Type: ApplicationFiled: December 10, 2014Publication date: April 2, 2015Inventors: Joseph COLLARD, Olga KHORKOVA SHERMAN
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Publication number: 20150093417Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the CD45 gene.Type: ApplicationFiled: December 2, 2014Publication date: April 2, 2015Inventors: Antonin de Fougerolles, Pamela Tan, Anna Borodovsky, Tatiana Novobrantseva, Sina Bavari, Kelly Lynn Warfield
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Publication number: 20150094236Abstract: A selectively inducible, single-stranded DNA (ssDNA) expression library, a method for constructing a ssDNA expression library, a method for screening ssDNA using the expression library, and a method for identifying ssDNA molecules that alter expression of bacterial and fungal gene(s) related to cell growth and toxin production and secretion. The screening library is used to, among other things, identify ODNs effective in stopping cell growth, killing bacteria or fungi, or preventing bacteria and/or fungi from synthesizing and secreting their toxins, and/or to discover ODNs effective in eukaryotic (e.g., mammalian) cells for targeted alteration of gene function. The library is also useful for identifying ssDNAs or ODNs that are used as therapeutic agents for, for instance, providing a method for treatment of bacterial infections such as sepsis.Type: ApplicationFiled: October 27, 2014Publication date: April 2, 2015Applicant: Star Biologics, Inc.Inventors: Yin Chen, Xin Xing Tan
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Publication number: 20150093403Abstract: The invention is directed to a isolated a canine circoviruses associated with canine respiratory and gastrointestinal disease, and isolated nucleic acids sequences and polypeptides thereof. The invention also relates to antibodies against antigens from canine circoviruses. The invention also relates to iRNAs which target nucleic acid sequences of the canine circovirus. The invention is related to methods for detecting the presence or absence of canine circoviruses in an animal. The invention is also related to immunogenic compositions for inducing an immune response against canine circoviruses in an animal.Type: ApplicationFiled: April 3, 2013Publication date: April 2, 2015Inventors: W. Ian Lipkin, Amit Kapoor, Edward J. Dubovi
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Publication number: 20150094357Abstract: There is provided herein methods and compositions for the diagnosis, prognosis and treatment of pancreatic cancer, along with methods of identifying anti-pancreatic cancer agents.Type: ApplicationFiled: December 9, 2014Publication date: April 2, 2015Applicant: THE OHIO STATE UNIVERSITY RESEARCH FOUNDATIONInventor: Carlo M. Croce
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Publication number: 20150094356Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Dystrophin family, in particular, by targeting natural antisense polynucleotides of Dystrophin family. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of DMD family.Type: ApplicationFiled: December 9, 2014Publication date: April 2, 2015Inventors: JOSEPH COLLARD, OLGA KHORKOVA SHERMAN
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Patent number: 8993532Abstract: Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Ago2 because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.Type: GrantFiled: April 22, 2011Date of Patent: March 31, 2015Assignee: Cold Spring Harbor LaboratoryInventors: Gregory J. Hannon, Sihem Cheloufi
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Patent number: 8993529Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of superoxide dismutase 1, soluble. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding superoxide dismutase 1, soluble. Methods of using these compounds for modulation of superoxide dismutase 1, soluble expression and for treatment of diseases associated with expression of superoxide dismutase 1, soluble are provided.Type: GrantFiled: January 10, 2011Date of Patent: March 31, 2015Assignee: Isis Pharmaceuticals, Inc.Inventors: C. Frank Bennett, Kenneth W. Dobie
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Patent number: 8993738Abstract: The present invention provides modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides and analogs thereof that are useful for incorporation at the terminus of an oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.Type: GrantFiled: April 26, 2011Date of Patent: March 31, 2015Assignee: Isis Pharmaceuticals, Inc.Inventors: Thazha P. Prakash, Punit P. Seth, Eric E. Swayze
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Patent number: 8993746Abstract: This invention relates to modified double-stranded oligoribonucleic acid (dsRNA) having improved stability in cells and biological fluids, and methods of making and identifying dsRNA having improved stability, and of using the dsRNA to inhibit the expression or function of a target gene.Type: GrantFiled: March 27, 2012Date of Patent: March 31, 2015Assignee: Alnylam Pharmaceuticals, Inc.Inventors: Hans-Peter Vornlocher, Ingo Roehl, Philipp Hadwiger, Tracy Stage Zimmermann, Muthiah Manoharan, Kallanthottathil G. Rajeev, Akin Akinc
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Patent number: 8993745Abstract: Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 19-23 nt short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3? ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.Type: GrantFiled: September 10, 2010Date of Patent: March 31, 2015Assignees: Max-Planck-Gesellschaft zur Förderung der Wissenschaften E.V., Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, University of MassachusettsInventors: Thomas Tuschl, Sayda Mahgoub Elbashir, Winfried Lendeckel
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Publication number: 20150087069Abstract: Isolated nucleic acid fragments comprising precursor miRNAs, and artificial miRNAs and their use in down-regulating gene expression are described.Type: ApplicationFiled: December 11, 2014Publication date: March 26, 2015Applicant: E. I. DU PONT DE NEMOURS AND COMPANYInventor: Brian McGonigle
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Publication number: 20150087691Abstract: Disclosed herein are methods for decreasing AIAT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of fibrosis. Disclosed herein are methods for decreasing AIAT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of liver disease, such as, AIATD associated liver disease, and pulmonary disease, such as, AIATD associated pulmonary disease in an individual in need thereof. Methods for inhibiting AIAT mRNA and protein expression can also be used as a prophylactic treatment to prevent individuals at risk for developing a liver disease, such as, AIATD associated liver disease and pulmonary disease, such as, AIATD associated pulmonary disease.Type: ApplicationFiled: March 19, 2013Publication date: March 26, 2015Applicant: ISIS PHARMACEUTICALS, INC.Inventors: Brett P. Monia, Michael L. McCaleb, Susan M. Freier, Shuling Guo
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Publication number: 20150087064Abstract: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. Catalytically inactive variants comprising deletions or other mutations are provided.Type: ApplicationFiled: June 27, 2014Publication date: March 26, 2015Inventor: Gregg B. Morin
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Publication number: 20150087695Abstract: Oligonucleotide compounds modulate expression and/or function of Erythropoietin (EPO) polynucleotides and encoded products thereof. Methods for treating diseases associated with Erythropoietin (EPO) comprise administering one or more oligonucleotide compounds designed to inhibit the EPO natural antisense transcript to patients.Type: ApplicationFiled: November 18, 2014Publication date: March 26, 2015Inventors: Joseph Collard, Olga Khorkova Sherman