Abstract: The present invention provides nucleic acid, vectors, viruses, and recombinant cells comprising triple-stranded structures, such as those resulting from central initiation and termination of HIV-1 reverse transcription at the center of HIV-1 linear DNA genomes. These triplex structures can act as a cis-determinant of HIV-1 DNA nuclear import, allowing infection of non-dividing target cells. In one aspect, the presence of the DNA triplex sequence in an HIV vector strongly stimulates gene transfer in hematopoietic stem cells. The invention also provides methods of using these triplex structures for making recombinant cells, as well as methods of using the recombinant cells to express proteins of interest both in vitro and in vivo.
Abstract: The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36? (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).
Type:
Grant
Filed:
December 17, 2018
Date of Patent:
September 10, 2019
Assignee:
ModernaTX, Inc.
Inventors:
Joshua Frederick, Ailin Bai, Vladimir Presnyak, Stephen Hoge, Kerry Benenato, Iain McFadyen, Ellalahewage Sathyajith Kumarasinghe, Susannah Hewitt
Abstract: The present invention concerns nanoparticles functionalized with duplex RNA for a variety of uses, including but not limited to gene regulation. More specifically, the disclosure provides a new strategy for conjugating RNA to a nanoparticle to achieve increased stability and activity.
Type:
Grant
Filed:
November 10, 2017
Date of Patent:
August 27, 2019
Assignee:
NORTHWESTERN UNIVERSITY
Inventors:
Chad A. Mirkin, David A. Giljohann, Dwight S. Seferos, Andrew E. Prigodich, Pinal C. Patel
Abstract: The present invention relates to the identification of a microRNA family, designated miR-29a-c, that is a key regulator of fibrosis in cardiac tissue. The inventors show that members of the miR-29 family are down-regulated in the heart tissue in response to stress, and are up-regulated in heart tissue of mice that are resistant to both stress and fibrosis. Also provided are methods of modulating expression and activity of the miR-29 family of miRNAs as a treatment for fibrotic disease, including cardiac hypertrophy, skeletal muscle fibrosis other fibrosis related diseases and collagen loss-related disease.
Type:
Grant
Filed:
June 30, 2017
Date of Patent:
August 27, 2019
Assignee:
THE BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
Abstract: The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotide molecules comprising an mRNA encoding an OX40L polypeptide. Also provided is a method for activating T cells or increasing the number of NK cells in a subject in need thereof.
Abstract: There are provided, inter alia, methods and compositions to treat autoimmune disease including invasiveness of fibroblast-like synoviocytes in rheumatoid arthritis.
Type:
Grant
Filed:
November 10, 2015
Date of Patent:
August 20, 2019
Assignee:
LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY
Abstract: The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotide molecules comprising an mRNA encoding an OX40L polypeptide. Also provided is a method for activating T cells or increasing the number of NK cells in a subject in need thereof.
Abstract: The present invention features a highly sensitive assay for detecting frameshift mutations for high throughput use. Also provided herein are methods for diagnosing or determining a predisposition for developing medullary cystic kidney disease type 1 (MCKD1) in a subject by detecting a frameshift mutation in the GC-rich variable number of tandem repeats (VNTR) sequence of the mucin 1 gene (MUC-1).
Type:
Grant
Filed:
February 10, 2015
Date of Patent:
August 6, 2019
Assignees:
THE BROAD INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION, INSTITUTO CARLOS SLIM DE LA SALUD, A.C.
Inventors:
Andrew Kirby, Andreas Gnirke, Brendan Blumenstiel, Matthew Defelice, Mark Daly
Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of a Collagen gene, in particular, by targeting natural antisense polynucleotides of a Collagen gene. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Collagen genes.
Abstract: The invention relates to the field of oligonucleotide therapeutics, and in particular to poly oligo oligonucleotides conjugates where two or more antisense oligonucleotides are covalently linked by physiologically labile linkers, and to a biocleavable functional group such as a conjugate group.
Type:
Grant
Filed:
January 26, 2015
Date of Patent:
July 23, 2019
Assignee:
Hoffmann-La Roche, Inc.
Inventors:
Nanna Albaek, Henrik Frydenlund Hansen, Susanne Kammler, Morten Lindow, Jacob Ravn, Mark Turner
Abstract: The present invention relates to a method for diagnosing lung cancers such as non-small lung cancer in a subject by using isocitrate dehydrogenase 1 as a diagnostic biomarker. The present invention also relates to a method for predicting the prognosis of the lung cancers such as non-small lung cancer in a subject by using isocitrate dehydrogenase 1 as a prognostic biomarker. The present invention further relates to a method of suppressing proliferation of lung tumor cells in a subject, decreasing growth of lung tumor cells in a subject, or improving survival of a subject with lung cancer by using isocitrate dehydrogenase 1 as a therapeutic target.
Type:
Grant
Filed:
September 28, 2017
Date of Patent:
July 23, 2019
Assignee:
Cancer Hospital, Chinese Academy of Medical Sciences
Inventors:
Jie He, Fengwei Tan, Zhaoli Chen, Nan Sun
Abstract: Methods of detecting or diagnosing posttraumatic stress disorder (PTSD) in a human subject are disclosed. In addition, methods of monitoring the progression of PTSD in a human subject, methods of treating a patient with PTSD, kits for diagnosing PTSD in a human subject suspected of having PTSD, and methods of detecting a microRA (miRNA) or plurality of miRNAs in a biological sample from a human subject are also disclosed.
Type:
Grant
Filed:
September 25, 2015
Date of Patent:
July 23, 2019
Assignee:
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
Abstract: The present invention relates to a pharmaceutical composition for treatment of cancer, which comprises, as an active ingredient, one or more miRNAs selected from the group consisting of miR-3670, miR-8078, and miR-4477a. The pharmaceutical composition for treatment of cancer according to the present invention exhibits excellent effects of inhibiting cancer cell proliferation and inducing cancer cell apoptosis. Thus, the pharmaceutical composition of the present invention can be effectively used as an anticancer therapeutic agent.
Type:
Grant
Filed:
February 25, 2016
Date of Patent:
July 16, 2019
Assignee:
BIONEER CORPORATION
Inventors:
Taewoo Lee, Sanghyung Shim, Ungsik Yu, Han Oh Park
Abstract: This invention relates to compounds, compositions, and methods useful for reducing lactate dehydrogenase target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.
Type:
Grant
Filed:
October 9, 2015
Date of Patent:
July 16, 2019
Assignee:
Dicerna Pharmaceuticals, Inc.
Inventors:
Bob D. Brown, Henryk T. Dudek, Cheng Lai
Abstract: The present disclosure relates to the use of nucleic acid (e.g., mRNA) combination therapies for the treatment of cancer. The disclosure provides compositions, and methods for their preparation, manufacture, and therapeutic use, wherein those compositions comprise at least two polynucleotides (e.g., mRNAs) in combination wherein the at least two polynucleotides are selected from the group consisting of (i) a polynucleotide encoding an immune response primer (e.g., IL23), (ii) a polynucleotide encoding an immune response co-stimulatory signal (e.g., OX40L), (iii) a polynucleotide encoding a checkpoint inhibitor (e.g., an anti CTLA-4 antibody), and, (iv) a combination thereof. The therapeutic methods disclosed herein comprise, e.g., the administration of a combination therapy disclosed herein for the treatment of cancer, e.g., by reducing the size of a tumor or inhibiting the growth of a tumor, in a subject in need thereof.
Type:
Grant
Filed:
June 1, 2018
Date of Patent:
July 2, 2019
Assignee:
ModernaTX, Inc.
Inventors:
Joshua P. Frederick, Susannah Hewitt, Ailin Bai, Stephen G. Hoge, Vladimir Presnyak, Iain McFadyen, Kerry Benenato, Ellalahewage Sathyajith Kumarasinghe
Abstract: The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36? (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).
Type:
Grant
Filed:
November 8, 2018
Date of Patent:
June 18, 2019
Assignee:
ModernaTX, Inc.
Inventors:
Joshua Frederick, Ailin Bai, Vladimir Presnyak, Stephen Hoge, Kerry Benenato, Iain Mcfadyen, Ellalahewage Sathyajith Kumarasinghe, Susannah Hewitt
Abstract: The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36? (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).
Type:
Grant
Filed:
December 13, 2018
Date of Patent:
June 18, 2019
Assignee:
ModernaTX, Inc.
Inventors:
Joshua Frederick, Ailin Bai, Vladimir Presnyak, Stephen Hoge, Kerry Benenato, Iain McFadyen, Ellalahewage Sathyajith Kumarasinghe, Susannah Hewitt
Abstract: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.
Type:
Grant
Filed:
April 19, 2016
Date of Patent:
June 11, 2019
Assignee:
Arrowhead Pharmaceuticals, Inc.
Inventors:
David L Lewis, David B Rozema, Darren H Wakefield, Torsten Hoffman, Erik Kitas, Peter Mohr, Philipp Hadwiger, Wilma Thuer, Linda Valis
Abstract: Some embodiments comprise methods, systems, and compositions to promote, improve and/or increase neuronal differentiation, oligodendrocyte differentiation, or neurological outcome or function in a patient in need thereof. Some embodiments also comprise the administration a composition comprising a pharmaceutically effective amount of one or more of a group comprising microRNA-146a, exosomes comprising microRNA-146a, a promoter of microRNA-146a expression, a microRNA-146a thymosin beta 4, and a phosphodiesterase 5 inhibitor to treat neurological conditions, diseases, or injuries in mammals, including in human beings.
Type:
Grant
Filed:
May 19, 2017
Date of Patent:
June 4, 2019
Assignee:
Henry Ford Health System
Inventors:
Xianshuang Liu, Zhenggang Zhang, Michael Chopp, Lei Wang, Benjamin A. L. Buller
Abstract: RNA interference (RNAi) triggers for inhibiting the expression of Factor XII (F12) gene through the mechanism of RNA interference are described. Pharmaceutical compositions comprising one or more F12 RNAi triggers together with one or more excipients capable of delivering the RNAi trigger(s) to a liver cell in vivo are also described. Delivery of the F12 RNAi trigger(s) to liver cells in vivo provides for inhibition of F12 gene expression and treatment of angioedema, including hereditary angioedema (HAE) and venous thromboembolism (VTE), and diseases associated with angioedema.
Type:
Grant
Filed:
September 26, 2017
Date of Patent:
June 4, 2019
Assignee:
Arrowhead Pharmaceuticals, Inc.
Inventors:
Steven B. Kanner, David L. Lewis, Darren H. Wakefield, Lauren J. Almeida