Abstract: The present invention provides an oligonucleotide which is capable of activating RIG-I and inducing an anti-viral, in particular, an IFN, response in cells expressing RIG-I. The present invention further provides an oligonucleotide which is capable of activating RIG-I and which has target gene-silencing activity. The oligonucleotide of the present invention has a double-stranded section of at least 19, preferably at least 21 bp, at least one 5? triphosphate, and at least one blunt end which bears a 5? triphosphate. The present invention further provides the use said oligonucleotide for inducing an anti-viral, in particular, an IFN, response in vitro and in vivo. The present invention additionally provides the use of said oligonucleotide for preventing and/or treating diseases or conditions such as infections, tumors/cancers, and immune disorders.
Abstract: A composition and method for replacement and regeneration of hair cells of the inner ear is provided. The composition comprises an active agent in an amount effective to decrease Hes1 gene expression in a tissue of the inner ear. The active agent can be short interfering RNA (siRNA) molecules encapsulated in a biodegradable nanoparticle. The method involves administering a solution to the inner ear where the solution contains an active agent in an amount effective to decrease Hes1 gene expression.
Abstract: The present invention relates to tolerogenic mammalian dendritic cells (iDCs) and methods for the production of tolerogenic DCs. In addition, the present invention provides methods for administration of tolerogenic dendritic cells as well as particles containing oligonucleotides to mammalian subjects. Enhanced tolerogenicity in a host can be useful for treating inflammatory and autoimmune related diseases, such as type 1 diabetes.
Type:
Grant
Filed:
November 18, 2014
Date of Patent:
August 8, 2017
Assignee:
University of Pittsburgh—Of the Commonwealth System of Higher Education
Abstract: Provided herein are signal activatable molecular constructs for delivery of molecules and related components, compositions, methods, and systems, having a 17 to 30 bp targeting domain duplex RNA, at least one protection strand having a protection segment and linker segment and a sensor strand having a displacement segment and a toehold segment, in which in an inactive conformation the protection segment and the displacement segment form a sensor domain duplex polynucleotide covalently attached to the targeting domain and presenting the toehold segment for binding to a signal molecule. In an active conformation the sensor strand is bound to the signal molecule and is detached from the at least one protection strand and from the targeting domain; and the targeting domain attaches the at least one protection strand in a configuration allowing processing by Dicer and/or an Argonaute enzyme.
Type:
Grant
Filed:
March 6, 2015
Date of Patent:
August 8, 2017
Assignees:
CALIFORNIA INSTITUTE OF TECHNOLOGY, CITY OF HOPE
Inventors:
Si-ping Han, William A. Goddard, III, Lisa Scherer, John J. Rossi
Abstract: The present disclosure relates to a method for treatment or prevention of diseases have an increased level of insulin-like growth factor I (IGF-I). The method comprises administration of a growth hormone (GH) variant having antagonistic activity in combination with an oligonucleotide targeted to growth hormone receptor (GHR) to a subject in need.
Abstract: Therapies and assays to screen for small molecules that can have therapeutic use in the control of neurodegenerative diseases such as Parkinson's and other alpha-synucleinopathies.
Type:
Grant
Filed:
January 4, 2016
Date of Patent:
July 18, 2017
Assignee:
RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
Abstract: The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.
Type:
Grant
Filed:
August 24, 2015
Date of Patent:
July 18, 2017
Assignee:
Ionis Pharmaceuticals, Inc.
Inventors:
Charles Allerson, Balkrishen Bhat, Ann B. Eldrup, Muthiah Manoharan, Richard H. Griffey, Brenda F. Baker, Eric E. Swayze
Abstract: The present invention relates to the use of inhibitors of leukotriene B4 receptor BLT2 for treating asthma. More particularly, the present invention relates to a pharmaceutical composition for treating asthma comprising BLT2 inhibitors and a method for treating asthma using BLT2 inhibitors.
Type:
Grant
Filed:
October 22, 2015
Date of Patent:
July 18, 2017
Assignee:
Korea University Research and Business Foundation
Abstract: This invention relates to compounds, compositions, and methods useful for reducing Glycolate Oxidase (HAO1) target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.
Abstract: The inhibitory oligonucleotides (ODNs) which strongly block NF-?B activation induced by TLR9 agonists and TLR7 agonists are provided. The production of proinflammatory cytokines, such as interleukin-6 and tumor necrosis factor alpha, is inhibited by the inhibitory-ODNs. Interferon production from human PBMC induced by TLR9 agonist is prevented by the inhibitory-ODNs. These ODNs can be used as a remedy for the treatment of immune-mediated disorders such as rheumatoid arthritis, systemic lupus erythematosus (SLE), sepsis, multiple organ dysfunction syndromes.
Abstract: The present invention relates to methods and compositions for the treatment of diseases, including cancer, infectious diseases and autoimmune diseases. The present invention also relates to methods and compositions for improving immune function. More particularly, the present invention relates to multifunctional molecules that are capable of being delivered to cells of interest for the treatment of diseases and for the improvement in immune function.
Type:
Grant
Filed:
October 11, 2013
Date of Patent:
June 27, 2017
Assignee:
CITY OF HOPE
Inventors:
Hua Yu, Marcin Kortylewski, Richard Jove, Piotr Marek Swiderski, John J. Rossi
Abstract: Provided is a novel method for the early detection and/or discrimination of cancer and anti-cancer agents for the prevention or early treatment of cancer. In particular, the method relates to the determination of levels of circulating miRNAs in breast cancer patients, both primary and metastatic. Furthermore, kits, devices, pharmaceutical compositions as well as methods related thereto are described.
Abstract: A recombinant nucleic acid comprising an aptamer that binds CD4 and an RNAi sequence that silences the expression of ROR?2 is described herein. Pharmaceutical compositions comprising the recombinant nucleic acid, particularly topical compositions are also described. Methods of treating inflammatory disease using the pharmaceutical composition are also described.
Abstract: The invention is directed to a method of characterizing a mechanism of action of an agent (e.g., a chemotherapeutic agent, a genotoxic agent). The method comprises contacting a plurality of populations of cells with an agent to be assessed, wherein each population of cells have one gene of interest targeted by a small hairpin RNA (shRNA) and wherein said gene of interest regulates cell death and a plurality of genes that regulate cell death are targeted in the plurality of populations of cells. A responsiveness of each population of cells to the agent is determined, thereby obtaining an shRNA signature of the agent, so as to identify one or more genes that mediate a response to the agent, thereby characterizing the mechanism of action of the agent. The invention is also directed an article of manufacture for characterizing a mechanism of action of a chemotherapeutic or genotoxic agent.
Type:
Grant
Filed:
December 16, 2011
Date of Patent:
June 20, 2017
Assignee:
Massachusetts Institute of Technology
Inventors:
Hai Jiang, Justin Pritchard, Douglas A. Lauffenburger, Michael Hemann
Abstract: In one aspect, the invention is directed to a method of characterizing a mechanism of action of a combination of agents. The method comprises contacting a plurality of populations of cells with a combination of agents to be assessed, wherein each population of cells have one gene of interest targeted by a small hairpin RNA (shRNA) and wherein the gene of interest regulates cell death and a plurality of genes that regulate cell death are targeted in the plurality of populations of cells. A responsiveness of each population of cells to the combination of agents is determined, thereby obtaining an shRNA signature of the combination of agents so as to identify one or more genes that mediate a response to the combination of agents, thereby characterizing the mechanism of action of the combination of agents.
Type:
Grant
Filed:
December 16, 2011
Date of Patent:
June 6, 2017
Assignee:
Massachusetts Institute of Technology
Inventors:
Justin Pritchard, Douglas A. Lauffenburger, Michael Hemann
Abstract: The present invention pertains to a novel pre-mRNA trans-splicing molecule (RTM) comprising a binding region which is complementary to a pre mRNA of a tumor associated gene, and a coding domain which encodes for a suicide gene. Specific embodiments of the present invention relate to RTMs which mediate trans-splicing of a suicide gene, such as thymidine kinase from herpes simplex virus (HSV-tk), with the pre mRNA of the squamous cell carcinoma associated gene solute carrier organic anion transporter family member 1B3 (SLCO1B3). The invention provides RTMs which selectively kill cells expressing SLCO1B3 and which are thus useful in the treatment of cancer, specifically squamous cell carcinoma associated with epidermolysis bullosa. Also provided are methods, kits and pharmaceutical compositions relating to the RTMs in accordance to the invention.
Abstract: The present invention relates to an RNAi-inducing nucleic acid molecule having a new structure and the use thereof, and more particularly to a novel nucleic acid molecule having a structure comprising a first strand, which is 24-121 nt in length and comprises a region complementary to a target nucleic acid, and a second strand which is 13-21 nt in length and has a region that binds complementarily to the region of the first strand, which is complementary to the target nucleic acid, so that the nucleic acid molecule inhibits the expression of a target gene with increased efficiency, and to a method of inhibiting the expression of a target gene using the nucleic acid molecule. The nucleic acid molecule structure of the present invention increases the efficiency with which the nucleic acid molecule inhibits the target gene.
Type:
Grant
Filed:
September 7, 2011
Date of Patent:
May 2, 2017
Assignee:
Sungkyunkwan University Foundation for Corporate Collaboration
Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ALAS1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of ALAS1.
Type:
Grant
Filed:
April 10, 2013
Date of Patent:
April 25, 2017
Assignees:
ALNYLAM PHARMACEUTICALS, INC., ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Inventors:
Brian Bettencourt, Kevin Fitzgerald, William Querbes, Makiko Yasuda, Robert J. Desnick