Abstract: The invention provides novel and versatile classes of riboregulators, including inter alia activating and repressing riboregulators, switches, and trigger and sink RNA, and methods of their use for detecting RNAs in a sample such as a well and in modulating protein synthesis and expression.
Type:
Grant
Filed:
September 16, 2021
Date of Patent:
October 17, 2023
Assignees:
President and Fellows of Harvard College, Trustees of Boston University
Inventors:
Alexander A. Green, Peng Yin, James J. Collins, Jongmin Kim
Abstract: Aspects of the invention provide single stranded oligonucleotides for activating or enhancing expression of MECP2. Further aspects provide compositions and kits comprising single stranded oligonucleotides for activating or enhancing expression of MECP2. Methods for modulating expression of MECP2 using the single stranded oligonucleotides are also provided. Further aspects of the invention provide methods for selecting a candidate oligonucleotide for activating or enhancing expression of MECP2.
Type:
Grant
Filed:
May 18, 2020
Date of Patent:
October 17, 2023
Assignee:
The General Hospital Corporation
Inventors:
Arthur M. Krieg, Romesh R. Subramanian, James McSwiggen, Jeannie T. Lee
Abstract: Provided herein are imaging probes and systems and methods employing such imaging probes for real-time, label-free, multiplexed imaging of RNAs in living cells. More particularly, aptamer-based sensors (“aptasensors”) and molecular fuses comprising multiple aptasensors are genetically encoded imaging probes comprising RNA-target binding sequence and an intramolecular reconfiguration sequence. The probe is configured such that binding of a RNA target by the RNA-target binding sequence triggers the intramolecular reconfiguration sequence to reconfigure such that an optically detectable output is generated by the probe.
Type:
Grant
Filed:
May 19, 2021
Date of Patent:
October 17, 2023
Assignee:
ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY
Abstract: An ANGPTL4 inhibitor consists of an oligonucleotide has 12 to 22 nucleotides. At least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of human and/or muse ANGPTL4 and inhibits the expression of ANGPTL4. A pharmaceutical composition can include the ANGPTL4 inhibitor and a pharmaceutically acceptable carrier, excipient diluent, or a combination of these.
Type:
Grant
Filed:
February 8, 2022
Date of Patent:
October 10, 2023
Assignee:
Lipigon Pharmaceuticals AB
Inventors:
Frank Jaschinski, Anne Sadewasser, Sven Michel
Abstract: Provided herein are RNA agent-loaded platelets, methods of preparing RNA agent-loaded platelets, and methods of using RNA agent-loaded platelets. In some embodiments, methods of loading RNA agents into platelets include treating platelets with a RNA agent, a cationic transfection reagent, and a loading buffer that can include a salt, a base, a loading agent, and optionally at least one organic solvent.
Type:
Grant
Filed:
November 27, 2019
Date of Patent:
September 26, 2023
Assignee:
Cellphire, Inc.
Inventors:
Keith Andrew Moskowitz, Amber Nicole Lee, Rafael Jorda
Abstract: The present invention provides a method for the early diagnosis, prognosis and differentiation of ischemic cardiac events in myocardial ischemia by a Nourin gene-based RNA molecular network of biomarkers to: (a) diagnose unstable angina and AMI (STEMI and NSTEMI) patients, and differentiate between unstable angina and AMI; (b) diagnose ACS patients and differentiate them from symptomatic non-cardiac patients and healthy subjects; (c) diagnose angina in suspected patients with history of chest pain and differentiate angina patients from symptomatic non-angina and healthy subjects; and (d) diagnose “new-onset” heart failure and provide a prognostic value and risk prediction of progression and deterioration, as well as monitoring patients' response to treatments. Downregulation of Nourin-related lncR-CTB9H12.
Abstract: 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.
Abstract: A multifunctional dendrimer nanoparticle and method of treating diseases of the posterior segment of the eye is presented. The functionalized polyamidoamine (PAMAM) dendrimer effectively delivers drugs and/or genes to the posterior eye, thereby providing for the effective, non-invasive, and topical treatment of diseased in the posterior eye. The multifunctional dendrimer nanoparticle has shRNA-encoding DNA and small molecule drug encapsulated cyclodextrin complexed to the outer surface of the dendrimer for delivery to the posterior segment of the eye.
Type:
Grant
Filed:
August 6, 2021
Date of Patent:
September 12, 2023
Assignees:
The United States Government as Represented by the Department of Veterans Affair, University of South Florida
Inventors:
Shyam S. Mohapatra, Subhra Mohapatra, Eleni Markoutsa
Abstract: Provided are compositions related to HSD17B13 variants, including nucleic acid molecules and polypeptides related to variants of HSD17B13, and cells comprising those nucleic acid molecules and polypeptides. Also provided are methods related to HSD17B13 variants. Such methods include methods for detecting the presence of the HSD17B13 rs72613567 variant in a biological sample comprising genomic DNA, for detecting the presence or levels of any one of variant HSD17B13 Transcripts C, D, E, F, G, and H, and particularly D, in a biological sample comprising mRNA or cDNA, or for detecting the presence or levels of any one of variant HSD17B13 protein Isoforms C, D, E, F, G, or H, and particularly D, in a biological sample comprising protein. Also provided are methods for determining a subject's susceptibility to developing a liver disease or of diagnosing a subject with liver disease.
Type:
Grant
Filed:
March 31, 2022
Date of Patent:
September 12, 2023
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Noura S. Abul-Husn, Omri Gottesman, Alexander Li, Xiping Cheng, Yurong Xin, Jesper Gromada, Frederick E. Dewey, Aris Baras, Alan Shuldiner
Abstract: The present invention relates to oligomeric compounds and conjugates thereof that target Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) PCSK9 mRNA in a cell, leading to reduced expression of PCSK9. Reduction of PCSK9 expression is beneficial for a range of medical disorders, such as hypercholesterolemia and related disorders.
Type:
Grant
Filed:
July 16, 2021
Date of Patent:
August 29, 2023
Assignee:
ROCHE INNOVATION CENTER COPENHAGEN A/S
Inventors:
Nanna Albæk, Maj Hedtjärn, Marie Wickstrom Lindholm, Niels Fisker Nielsen, Andreas Petri, Jacob Ravn
Abstract: Methods of minimizing dysregulation of Staufen1-associated RNA metabolism can include introducing an amount of a Staufen1-regulating agent to a target cell sufficient to minimize the dysregulation. Therapeutic compositions for treating a neurodegenerative condition associated with Staufen1-induced dysregulation of RNA metabolism can include a therapeutically effective amount of a Staufen1-regulating agent and a pharmaceutically acceptable carrier.
Type:
Grant
Filed:
December 8, 2017
Date of Patent:
August 15, 2023
Assignee:
University of Utah Research Foundation
Inventors:
Stefan M. Pulst, Daniel R. Scoles, Sharan Paul
Abstract: The invention provides an siRNA against protein S for use in a method of treatment of hemophilia. Also within the scope of the present invention is a method for treating hemophilia in a patient in need thereof, comprising administering to the patient a molecule comprising a siRNA according to the invention, and a dosage form for the prevention or treatment of hemophilia, comprising a molecule comprising a siRNA according to the invention.
Type:
Grant
Filed:
November 2, 2017
Date of Patent:
August 15, 2023
Assignee:
Universität Bern
Inventors:
Raja Prince El Adnani, Anne Angelillo-Scherrer
Abstract: The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the TMPRSS6 gene, and methods of using such RNAi agents to inhibit expression of TMPRSS6 and methods of treating subjects having a TMPRSS6 associated disorder, e.g., an iron overload associated disorder, such as ?-thalassemia or hemochromatosis.
Type:
Grant
Filed:
October 5, 2020
Date of Patent:
August 15, 2023
Assignee:
Alnylam Pharmaceuticals, Inc.
Inventors:
James Butler, Martin A. Maier, Kevin Fitzgerald, Shannon Fishman, Donald Foster, Vasant R. Jadhav, Stuart Milstein
Abstract: Provided herein are methods, compounds, and compositions for reducing expression of GYS1 in an individual. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a glycogen storage disease or disorder in an individual in need.
Type:
Grant
Filed:
December 23, 2021
Date of Patent:
August 1, 2023
Assignees:
Ionis Pharmaceuticals, Inc., The Hospital for Sick Children
Inventors:
Tamar R. Grossman, Susan M. Freier, Berge Minassian, Saija Ahonen
Abstract: The compositions and methods of the invention provide compositions and methods for preferential targeting of tissues to delivery therapeutic or diagnostic agents. For example, such compounds are useful in the treatment of joint disorders those affecting articulating joints, e.g., injury-induced osteoarthritis as well as autoimmune diseases affecting joint tissue such as rheumatoid arthritis.
Abstract: The current invention provides a method of activating fibroblast and myofibroblast apoptosis in a tissue of a mammal, comprising administering to the tissue a therapeutically effective amount of a composition comprising an siRNA molecule that binds to an mRNA that codes for TGFB1 protein in a mammalian cell, an siRNA molecule that binds to an mRNA that codes for COX-2 protein in a mammalian cell, and a pharmaceutically acceptable carrier comprising a pharmaceutically acceptable histidine-lysine polymer. The invention also provides additional methods for using this composition.
Type:
Grant
Filed:
October 30, 2017
Date of Patent:
July 11, 2023
Assignees:
Sirnaomics, Inc., Sirnaomics Medicine Technology (Suzhou) Co, Ltd.
Inventors:
John Xu, Patrick Y. Lu, Jia Zhou, Qingfeng Li, Vera Simonenko
Abstract: A construct, or a pharmaceutically acceptable salt thereof, comprising: (a) a polyethylene glycol-block-poly(L-lysine) polymer moiety, wherein the polyethylene glycol is thiol-functionalized; (b) a cholecystokinin-B (CCK-B) receptor ligand coupled to the polyethylene glycol of the polymer moiety; and (c) a siRNA complexed with the poly(L-lysine) of the polymer moiety, wherein the construct is neutralized.
Type:
Grant
Filed:
December 17, 2021
Date of Patent:
July 11, 2023
Assignees:
Georgetown University, The United States of America, as represented by the Secretary, Department of Health and Human Services
Inventors:
Jill P. Smith, Stephan Stern, Abdullah Mahmud
Abstract: Nuclease-mediated methods for expanding repeats already present at a genomic locus are provided. Non-human animal genomes, non-human animal cells, and non-human animals comprising a heterologous hexanucleotide repeat expansion sequence inserted at an endogenous C9orf72 locus and methods of making such non-human animal cells and non-human animals through nuclease-mediated repeat expansion are also provided. Methods of using the non-human animal cells or non-human animals to identify therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative disorders associated with repeat expansion at the C9orf72 locus are also provided.
Type:
Grant
Filed:
December 13, 2019
Date of Patent:
July 4, 2023
Assignee:
Regeneran Pharmaceuticals, Inc.
Inventors:
Daisuke Kajimura, Aarti Sharma-Kanning, Brittany Dubose, Gustavo Droguett, Chia-Jen Siao, Junko Kuno, David Frendewey, Brian Zambrowicz