Abstract: A nucleoside derivative represented below, or a salt thereof. (In (1), R1 represents a hydrogen atom, a hydroxyl group or a protected group, and in (2), X represent a halogen atom. In (1) and (2), R2 and R4 each represent a hydrogen atom, a hydroxyl protecting, phosphate, or protected phosphate group, or —P(?O)nR5R6 (n is 0 or 1, R5 and R6 each representing a hydrogen atom, hydroxyl, protected hydroxyl, mercapto, protected mercapto, lower alkoxy, cyano lower alkoxy, amino or substituted amino group, when n is 1, R5 and R6 are not both hydrogen atoms), R3 represents NHR7 (R7 represents a hydrogen atom, alkyl, alkenyl or protecting group for an amino group), an azide, amidino or guanidino group, each having a linking group (when R7 is hydrogen atom, the linking group is an alkylene group), and B represents any of a purine-9-yl, 2-oxo-pyrimidin-1-yl, substituted purine-9-yl or substituted 2-oxo-pyrimidin-1-yl group).
Type:
Grant
Filed:
December 14, 2017
Date of Patent:
May 9, 2023
Assignee:
NATIONAL UNIVERSITY CORPORATION TOKAI NATIONAL HIGHER EDUCATION AND RESEARCH SYSTEM
Abstract: The present invention relates to a use of CD133 involved in resistance to an EGFR-targeting agent in colon cancer. The CD133 protein may be used as a novel target protein for diagnosing and treating resistant cancer as well as general cancer.
Type:
Grant
Filed:
April 14, 2020
Date of Patent:
May 2, 2023
Assignee:
Korea University Research and Business Foundation
Abstract: There is a method for selective translation of a desired protein. The method has the steps of (a) providing a modified nucleic acid enzyme, including two half cores of a minimized 9DB1 deoxyribozyme split between nucleotides 35 and 39, wherein each half core includes a pendant assembly arm of a strand of nucleic acids extending therefrom and a separate, pendant binding arm extending therefrom of a strand of nucleic acids; (b) binding a nucleic acid ligand to each of the two assembly arms to form an intermediate; (c) binding the intermediate to (i) a first substrate of ribonucleic acid sequences capped at one end, (ii) a second substrate of a strand of ribonucleic acids having a 5? triphosphate region at one end and a region of polyadenylated nucleotides at the other end and wherein the second substrate codes for the desired protein, (iii) join the two half cores to form a core in order to form a ligated product; and (d) allowing the translation for the desired protein to proceed from the ligated product.
Abstract: The present invention relates functional ligands to target molecules, particularly to functional nucleic acids and modifications thereof, and to methods for simultaneously generating, for example, numerous different functional biomolecules, particularly to methods for generating numerous different functional nucleic acids against multiple target molecules simultaneously. The present invention further relates to functional ligands which bind with affinity to target molecules, such as antibiotics, such as colistin.
Type:
Grant
Filed:
February 22, 2020
Date of Patent:
March 21, 2023
Assignee:
BASE PAIR BIOTECHNOLOGIES, INC.
Inventors:
Robert Batchelor, George W. Jackson, Truong Nguyen, Vinoth Sankarapani
Abstract: The present invention relates to the field of recombining production of biological molecules in host cells. The invention provides nucleic acid constructs that allow to modify expression of a desired gene using both in vitro and in vivo gene expression systems. The constructs can advantageously be used to produce a variety of biological molecules recombinantly in industrial scales, e.g. human milk oligosaccharides (HMO).
Abstract: Embodiments of the disclosure include compositions and methods for generating RNA nanostructures, particularly in a cell. In particular embodiments, RNA subunits comprising at least one three-way junction and at least one kissing loop are configured such that multiple RNA subunits can polymerize into a specific structure. In particular embodiments, the RNA subunits are configured such that sequence of at least one kissing loop is complementary to sequence of another kissing loop, such as on another RNA subunit, and the summation of multiple RNA subunits having specific individual structures results in a combined polymerized structure of a defined shape. In specific embodiments, an RNA nanostructure generated from methods herein is utilized for an application, such as manufacturing or genetic modifications in a cell.
Abstract: The invention relates to a nucleic acid aptamer with the capability of binding specifically to a and inhibiting TLR-4, to a complex comprising said aptamer and a functional group, as well as to pharmaceutical compositions thereof. The invention also relates to uses and methods for detecting TLR-4 and to uses and methods for inhibiting TLR-4. Finally, the invention also relates to an aptamer for use in manufacturing a drug for the treatment of a pathology characterized by an increase in expression of TLR4 and/or an increase in activation of TLR-4.
Type:
Grant
Filed:
September 16, 2020
Date of Patent:
February 28, 2023
Assignee:
APTATARGETS, S.L.
Inventors:
Ignacio Lizasoain Hernandez, Victor Manuel Gonzalez Muñoz, Geronimo Fernandez Gomez-Chacon, Maria Angeles Moro Sanchez, Maria Elena Martin Palma, Ana Moraga Yebenes
Abstract: The present invention includes methods for detecting and reducing or inhibiting ischemic stroke in a mammal, the method comprising: (a) selecting microRNAs to downregulate selected from the group consisting of hsa-miR-96-5p, hsa-miR-99a-5p, hsa-miR-122-5p, hsa-miR-186-5p, hsa-miR-211-5p, hsa-mir-760, PC-3p-57664, or PC-5p-12969, (b) selecting microRNAs to upregulate selected from the group consisting of ggo-miR-139, hsa-miR-30d-5p, hsa-miR-22-3p, hsa-miR-23a-3p, mmu-miR-5124a, mmu-mir-6240-5p, PC-3p-32463, or PC-5p-211, and combinations thereof, and (c) administering an agent that: downregulates that targets in (a), upregulates the targets in (b), or both, to the subject in an amount sufficient to reduce or inhibit ischemic stroke in the mammal. The present invention also includes the detection of the markers for use with stroke patients.
Abstract: The present disclosure provides materials and methods for the delivery of therapeutic nucleic cells (and imaging agents) to tissues.
Type:
Grant
Filed:
May 8, 2019
Date of Patent:
February 21, 2023
Assignees:
UNIVERSITY OF MIAMI, UNIVERSITY OF MODENA AND REGGIO EMILLA—UNIMORE
Inventors:
Paolo Serafini, Dimitri Van Simaeys, Adriana De La Fuente, Alessia Zoso, Silvio Bicciato, Jimmy Caroli, Cristian Taccioli, Andrea Grilli, Midhat Abdulreda
Abstract: The present invention is related to a method for treating cancer by using siRNA nanocomplex consisting of a nucleic acid molecule, a monocationic drug and a biocompatible polymer surfactant. The present nanocomplex can deliver an active ingredient (for example, a nucleic acid molecule and monocationic drug) into a cell/tissue of interest in a stable manner, and may be effectively applied for treating or detecting diverse disorders (practically, cancers).
Abstract: This disclosure relates to oligonucleotides, compositions and methods useful for reducing GYS2 expression, particularly in hepatocytes. Disclosed oligonucleotides for the reduction of GYS2 expression may be double-stranded or single-stranded, and may be modified for improved characteristics such as stronger resistance to nucleases and lower immunogenicity. Disclosed oligonucleotides for the reduction of GYS2 expression may also include targeting ligands to target a particular cell or organ, such as the hepatocytes of the liver, and may be used to treat glycogen storage diseases (e.g., GSDIa, GSDIII, GSDIV, GSDVI, and GSDIX) and related conditions.
Type:
Grant
Filed:
February 15, 2019
Date of Patent:
February 7, 2023
Assignee:
Dicerna Pharmaceuticals, Inc.
Inventors:
Bob D. Brown, Natalie Pursell, Henryk T. Dudek, Cheng Lai
Abstract: The invention provides inducible promoter systems and their components incorporating components of a tetracycline operon. By coordinating expression of different transcriptional units in these systems as a result of selection of promoters and/or linking the units into the same DNA molecule, these systems can achieve higher levels of expression of coding segments of interest, increased differential levels of expression between on- and off-states, and/or greater responsiveness to inducing agents than conventional systems.
Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable proteins, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and, in certain instances, cleavage activity of RNA-programmable proteins (e.g., RNA-programmable endonucleases). By incorporating ligand-responsive self-cleaving catalytic RNAs (aptazymes) into guide RNAs, a set of aptazyme-embedded guide RNAs was developed that enable small molecule-controlled nuclease-mediated genome editing and small molecule-controlled base editing, as well as small molecule-dependent transcriptional activation in mammalian cells.
Type:
Grant
Filed:
May 11, 2018
Date of Patent:
January 24, 2023
Assignee:
President and Fellows of Harvard College
Inventors:
Weixin Tang, Johnny Hao Hu, David R. Liu
Abstract: An inhibitor for use for preventing and/or treating an infection with hepatitis B virus (HBV) and an in vitro screening method for the identification of a candidate compound suitable for preventing and/or treating an infection with hepatitis B virus is provided.
Type:
Grant
Filed:
August 31, 2018
Date of Patent:
January 17, 2023
Assignees:
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM), HOSPICES CIVILS DE LYON, CENTRE LÉON-BÉRARD, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, UNIVERSITÉ CLAUDE BERNARD LYON 1
Inventors:
Jean Pierre Quivy, Barbara Testoni, Fabien Zoulim, Maelle Locatelli
Abstract: The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.
Type:
Grant
Filed:
May 19, 2022
Date of Patent:
January 10, 2023
Assignee:
ARROWHEAD PHARMACEUTICALS, INC.
Inventors:
Anthony Nicholas, Tao Pei, Zhao Xu, Daniel Braas, Zhi-Ming Ding
Abstract: Compositions and methods for introducing double-stranded breaks within the SERPINA1 gene are provided. Compositions and methods for reducing and eliminating mutant forms of ?1-antitrypsin (AAT), such as seen in subjects having ?1-antitrypsin deficiency (AATD), are provided.
Type:
Grant
Filed:
June 20, 2019
Date of Patent:
January 10, 2023
Assignee:
Intellia Therapeutics, Inc.
Inventors:
Shobu Odate, Walter Strapps, Reynald Michael Lescarbeau
Abstract: Disclosed are methods of using a microRNA-210 inhibitor in preparation of drugs for treating inflammatory skin diseases. The present inventor has demonstrated through a large number of experiments that in vitro inhibition of microRNA-210 expression can significantly enhance the expression of its target gene STAT6, thereby inhibiting proliferation and chemokine CCL20 secretion of keratinocytes, further inhibiting chemotactic T cell migration towards skin lesion, and also inhibiting differentiation of TH1 and TH17. MicroRNA-210 knockout and intradermal injection of a microRNA-210 inhibitor (cholesterol-modified antagomiR-210) on a skin lesion specifically inhibit the expression of microRNA-210, so that skin inflammation in mice can be significantly inhibited, and T cell immune imbalance is mitigated. The present invention provides a new pathophysiological mechanism for inflammatory skin diseases and provides a new strategy for preparing drugs for treating inflammatory skin diseases.
Type:
Grant
Filed:
January 24, 2019
Date of Patent:
January 3, 2023
Assignee:
THE SECOND XIANGYA HOSPITAL OF CENTRAL SOUTH UNIVERSITY
Inventors:
Qianjin Lu, Ming Zhao, Yuwen Su, Ruifang Wu
Abstract: Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof.
Type:
Grant
Filed:
June 1, 2020
Date of Patent:
December 27, 2022
Assignee:
Ionis Pharmaceuticals, Inc.
Inventors:
Brett P. Monia, Susan M. Freier, Andrew M. Siwkowski, Shuling Guo
Abstract: A method for identifying a compound that prevents, ameliorates and/or inhibits a hepatitis B virus (HBV) infection is provided, wherein a compound that reduces the expression and/or activity of PAP associated domain containing 5 (PAPD5) and/or PAP associated domain containing 7 (PAPD7) is identified as a compound that prevents, ameliorates and/or inhibits a HBV infection. Inhibitors of PAPD5 or PAPD7 are provided for use in treating and/or preventing a HBV infection; as well as a combined preparation comprising an inhibitor of PAPD5 and an inhibitor of PAPD7 for simultaneous or sequential use in the treatment or prevention of a HBV infection.
Type:
Grant
Filed:
June 19, 2017
Date of Patent:
December 27, 2022
Assignee:
HOFFMANN-LA ROCHE INC.
Inventors:
Hassan Javanbakht, Søren Ottosen, Lykke Pedersen, Henrik Mueller