Abstract: Methods and compositions for inhibiting tumorigenicity both in vitro and in vivo in a subject in need thereof, comprising administering an effective amount of an anti-miR-494 nucleic acid construct sufficient to target one or more tumor suppressor genes (TSGs) are described. Activation of the ERK1/2 pathway is a major determinant of diverse cellular processes and cancer development and is responsible for the transcription of several important miRNAs. Described herein is a link between the ERK1/2 pathway and BIM expression through miR-494. This ERK1/2 pathway regulates apoptosis and cell proliferation through miR-494 and mechanisms responsible for TRAIL resistance. Materials and methods related to the study and treatment of cancer are described.
Abstract: The present invention relates to transposon activation and mobilization, particularly in the brain, during normal aging; reporter systems to detect such mobilization, along with cells and transgenic animals containing such systems; methods of monitoring neuronal function during normal aging; methods of determining the risk of age-related neuronal decline and age-related mortality; and the use of transposon inhibitors and apoptosis inhibitors to delay age-related neuronal decline and age-related mortality.
Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the CD274/PD-L1 gene, and methods of using such dsRNA compositions to inhibit expression of CD274/PD-L1.
Type:
Grant
Filed:
July 10, 2013
Date of Patent:
August 23, 2016
Assignee:
Alnylam Pharmaceuticals
Inventors:
Antonin DeFougerolles, Tatiana Novobrantseva, Brian Bettencourt
Abstract: Antisense compositions targeted against an mRNA sequence coding for a selected protein, at a region having its 5? end from 1 to about 25 base pairs downstream of a normal splice acceptor junction in the preprocessed mRNA, are disclosed. The antisense compound is RNase-inactive, and is preferably a phosphorodiamidate-linked morpholino oligonucleotide. Such targeting is effective to inhibit natural mRNA splice processing, produce splice variant mRNAs, and inhibit normal expression of the protein.
Abstract: The present disclosure provides methods and compositions to selectively modulate RNA processing. The methods and compositions selectively enhance or repress RNA processing by up- or down-regulating Drosha expression and/or by providing RNA sequences with mis-matches introduced or removed 5 and/or 9-12 nucleotide positions from the Drosha cutting site. Therapeutic uses of the methods and compositions are also described.
Type:
Grant
Filed:
December 18, 2013
Date of Patent:
August 16, 2016
Assignee:
UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION
Inventors:
Hannele Ruohola-Baker, Pratyusha Banik, Alan Beem, Sandra Shannon, Henrik Sperber
Abstract: Disclosed herein are methods of treating a patient at risk of developing or having a neurofibromatosis or a sporadic schwannoma. In exemplary embodiments, the method involves administering to a subject in need an effective amount of a LIMK modulating agent. Also disclosed are compounds newly identified to be inhibitors of Merlin-null Schwann cell proliferation and/or survival.
Type:
Grant
Filed:
March 13, 2013
Date of Patent:
August 9, 2016
Assignee:
University of Central Florida Research Foundation, Inc.
Abstract: Inhibitors of miRNAs 221 and 222, and their use as medicaments in the treatment of multiple myeloma. The inhibitors inhibit miRNAs 221 and 222 of the type of LNA-miRNAs and have the formula +C*A*G*+A*+C*A*+A*T*+G*T*+A*+G*C, and formula C*+A*+G*+A*T*+G*T*+A*+G*C wherein letters with symbol “+” indicate the positions of LNA and symbol “*” indicates phosphorothioate bonds.
Type:
Grant
Filed:
July 14, 2015
Date of Patent:
August 2, 2016
Inventors:
Pierfrancesco Tassone, Pierosandro Tagliaferri, Maria Teresa Di Martino
Abstract: Provided herein are methods, compounds, and compositions for reducing expression of PTP1B 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.
Abstract: The present disclosure relates to a nucleic acid assembly (NAA), comprising sensor domain and handle domain; an assembly interfaceable motif (AIM) sequence optionally along with intracellular targeting motif (ITM) sequence; and an AIM-NAA complex. It also relates to a vector comprising assembly interfaceable motif sequence optionally along with intracellular targeting motif sequence and a cell comprising the vector. Further, the instant disclosure also provides a method to obtain the nucleic acid assembly, method of intracellular targeting and kit thereof.
Abstract: Embodiments of the invention provide a method detecting and treating cancer, such as lung cancer. In some aspects, the method may include detecting cancer in a subject, which may comprise assessing the expression of a marker in a sample from the subject. For example, the marker may comprise c-Met and/or Fn14. In some embodiments, if the subject is diagnosed as having cancer, the method may further provide administering a therapeutically effective amount of a substance that reduces the expression level of Fn14 to the subject to reduce the invasive and migratory capabilities of the cancer.
Type:
Grant
Filed:
December 5, 2014
Date of Patent:
August 2, 2016
Assignee:
The Translational Genomics Research Institute
Abstract: Therapeutic agents which target heat shock protein (hsp) 27 in vivo are used to provide treatment to individuals, particularly human individuals, suffering from prostate cancer and other cancers that overexpress hsp27. A therapeutic agent, for example an antisense oligonucleotide or RNAi nucleotide inhibitor with sequence specificity for hsp27 mRNA, for example human hsp27 mRNA, is administered to an individual suffering from prostate cancer or some other cancer expressing elevated levels of hsp 27 in a therapeutically effective amount. The therapeutic agent is suitably formulated into a pharmaceutical composition which includes a pharmaceutically acceptable carrier, and packaged in dosage unit form. A preferred dosage unit form is an injectable dosage unit form.
Type:
Grant
Filed:
April 29, 2015
Date of Patent:
August 2, 2016
Assignee:
The University of British Columbia
Inventors:
Martin E. Gleave, Palma Rocchi, Maxim Signaevsky, Eliana Beraldi
Abstract: The present invention is directed to nucleic acid molecules containing a loop sequence designed to circumvent exportin-5 mediated export, and methods using these novel molecules.
Abstract: The present invention relates to methods, kits and compositions to treat hypertension and other cardiovascular diseases in a subject, in particular, a method of treating or preventing a cardiovascular disease in a subject comprising administering to a subject at least one anti-miR agent to miRNA-425. In some embodiments, an anti-miR agent is a small molecule or an oligonucleotide complementary to at least part of the miR-425 of SEQ ID NO: 1, or an anti-miR complementary to at least part of the miRNA seed sequence AUGACA (SEQ ID NO: 2). Another aspect of the present invention relates to methods, kits and compositions to treat low blood pressure in a subject comprising administering a composition comprising a miR-425 agent to decrease ANP levels in the subject.
Type:
Grant
Filed:
June 14, 2013
Date of Patent:
July 12, 2016
Assignee:
The General Hospital Corporation
Inventors:
Kenneth D. Bloch, Pankaj Arora, Christopher Newton-Cheh, Thomas J. Wang
Abstract: Oligonucleotides bearing free, uncapped 5? phosphate group(s) are recognized by RIG-I, leading to the induction of type I IFN, IL-18 and IL-1? production. Bacterial RNA also induces type I IFN production. 5? phosphate oligonucleotides and bacterial RNA can be used for inducing an anti-viral response or an anti-bacterial response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in vitro and in vivo and for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, tumors, allergies, autoimmune diseases, immunodeficiencies and immunosuppression. Single-stranded 5? triphosphate RNA can be used for inducing an anti-viral response, an anti-bacterial response, or an anti-tumor response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in a target cell-specific manner.
Abstract: The invention relates to isolated DNA or RNA molecules comprising at least ten contiguous bases having a sequence in a pancreatic islet microRNA. In another embodiment, the invention relates to isolated single stranded pancreatic islet microRNA molecules or anti-pancreatic islet microRNA molecules.
Type:
Grant
Filed:
November 30, 2015
Date of Patent:
July 5, 2016
Assignee:
The Rockefeller University
Inventors:
Markus Stoffel, Matthew N. Poy, Thomas H. Tuschl
Abstract: The present disclosure relates to RNAi agents useful in methods of treating BetaENaC-related diseases such as cystic fibrosis, pseudohypoaldosteronism type 1 (PHA1), Liddle's syndrome, hypertension, alkalosis, hypokalemia, and obesity-associated hypertension, using a therapeutically effective amount of a RNAi agent to Beta-ENaC.
Type:
Grant
Filed:
May 28, 2015
Date of Patent:
June 28, 2016
Assignee:
Arrowhead Pharmaceuticals, Inc.
Inventors:
Antonin De Fougerolles, John Louis Diener, Emma Hickman, Gregory Hinkle, Stuart Milstein, Anne-Marie Pulichino, Andrew Griffin Sprague
Abstract: The present invention concerns methods and compositions for diagnosing and/or treating vascular diseases including cancer, cardiac diseases, vascular diseases of the eye, and inflammatory diseases. The methods involve measuring the levels of one or multiple miRNAs in patient samples and using the test results to diagnose and/or predict an optimal treatment regimen for the patient. Compositions described in the invention include nucleic acids that function as miRNAs or miRNA inhibitors that can be introduced to a patient to reduce or increase vascularization as needed.
Type:
Grant
Filed:
May 5, 2015
Date of Patent:
June 14, 2016
Assignee:
MIRNA THERAPEUTICS, INC.
Inventors:
Jikui Shen, Kevin Kelnar, Jeffrey Shelton, David Brown, Peter Campochiaro
Abstract: The invention provides for LNA oligomers, for the treatment of a metabolic or liver disorder, wherein the LNA oligomer is administered orally in a unit dose of less than 50 mgs/kg, wherein the LNA oligomer is administered in the presence of a penetration (permeation) enhancer.
Type:
Grant
Filed:
October 20, 2010
Date of Patent:
June 14, 2016
Assignee:
Roche Innovation Center Copenhagen A/S
Inventors:
Gregroy Hardee, Ellen Marie Straarup, Marie Wickstrom Lindholm, Henrik Orum, Henrik Hansen
Abstract: MicroRNAs (miRNAs) are a diverse and abundant class of ˜22-nucleotide (nt) endogenous regulatory RNAs that play a variety of roles in animal cells by controlling gene expression at the posttranscriptional level. Increased miR-181a expression in mature T cells is shown to cause a marked increase in T cell activation and augments T cell sensitivity to peptide antigens. Moreover, T cell blasts with higher miR-181a expression become reactive to antagonists. The effects of miR-181a on antigen discrimination are in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway, including PTPN22 and the dual specificity phosphatases DUSP5 and DUSP6. This results in a reduction in the TCR signaling threshold, thus quantitatively and qualitatively enhancing T cell sensitivity to antigens.
Type:
Grant
Filed:
May 27, 2014
Date of Patent:
June 14, 2016
Assignee:
The Board of Trustees of the Leland Stanford Junior University
Inventors:
Qi-Jing Li, Chang-Zheng Chen, Mark M. Davis, Jacqueline Chau