Patents Assigned to THE BROAD INSTITUTE, INC.
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Publication number: 20240150277Abstract: The present invention includes compounds of formula (I) and methods for its preparation and treatment of disorders with activated peroxisome preoliferator-activated receptor gamma (PPARG), particularly cancer.Type: ApplicationFiled: August 31, 2023Publication date: May 9, 2024Applicants: Bayer Aktiengesellschaft, The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.Inventors: Stephan SIEGEL, Knut EIS, Timo STELLFELD, Léa Aurelie BOUCHÉ, Elisabeth POOK, Joseph Peter BLUCK, Philip LIENAU, Constantia PANTELIDOU, Isabel Sophie JERCHEL-FURAU, Ulf BRÜEGGEMEIER, Sven CHRISTIAN, Detlev SÜLZLE, Anders Roland FRIBERG, Simon HOLTON, Christian LECHNER, Stefan KAULFUSS, Hanna MEYER, Douglas ORSI, Steven James FERRARA, Jonathan GOLDSTEIN, Matthew MEYERSON, Christopher LEMKE
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Publication number: 20240144704Abstract: The present disclosure provides methods for identifying cells in an image. An apparatus for identifying cells in an image is also provided by the present disclosure. Further provided herein is a non-transitory computer-readable storage medium for performing the methods disclosed herein. Methods of diagnosing a disease or disorder and of treating a disease or disorder in a subject using the methods disclosed are also provided herein.Type: ApplicationFiled: February 18, 2022Publication date: May 2, 2024Applicants: c/o The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Xiao Wang, Jia Liu, Yichun He
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Patent number: 11965159Abstract: Compositions and methods for conditionally regulating activities of CRISPR-Cas systems. In some embodiments, the methods comprise providing an inactive guide RNA comprising a regulatory domain bound by a lock nucleic acid different from the guide RNA; and displacing the lock nuclei acid from the regulatory domain by a trigger nucleic acid, thereby activating the guide RNA, wherein the activated guide RNA forms a complex with a Cas enzyme.Type: GrantFiled: January 29, 2020Date of Patent: April 23, 2024Assignees: The Broad Institute, Inc., The Brigham and Women's Hospital, Inc., The Regents of the University of CaliforniaInventors: Amit Choudhary, Kurt Cox, Hari Subramanian, Elisa Franco
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Publication number: 20240124924Abstract: The present disclosure relates to methods and compositions for enhanced assessment of exogenous polynucleotide and/or polypeptide-mediated transcriptional perturbations at high throughput and single cell/droplet levels of resolution. In embodiments, nucleic acid fusions of exogenous polynucleotide(s) and associated target transcript(s) are produced within individually sequestered or discretely identifiable cells/lysates and analyzed for exogenous polynucleotide mediated perturbations across a vast population of droplets/cells within individual reactions. Kits for performance of the methods are also provided.Type: ApplicationFiled: February 22, 2022Publication date: April 18, 2024Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, THE GENERAL HOSPITAL CORPORATIONInventors: Aziz Al'Khafaji, Frances Keer, Paul Blainey, Nir Hacohen
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Publication number: 20240124866Abstract: The disclosure provides methods and compositions for treating blood diseases/disorders, such as sickle cell disease, hemochromatosis, hemophilia, and beta-thalassemia. For example the disclosure provides therapeutic guide RNAs that target the promotor of HBG1/2 to generate point mutations that increase expression of fetal hemoglobin. As another example, the disclosure provides therapeutic guide RNAs that target mutations in HBB, Factor VIII, and HFE to treat sickle cell disease, beta-thalassemia, hemophilia and hemochromatosis. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins are in complex with nucleic acids, such as guide RNAs (gRNAs), which target the fusion proteins to a DNA sequence (e.g., an HBG1 or HBG2 protmoter sequence, or an HFE, GBB, or F8 gene sequence).Type: ApplicationFiled: September 1, 2023Publication date: April 18, 2024Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, Beam Therapeutics Inc.Inventors: David R. Liu, Nicole Marie Gaudelli, Michael S. Packer, Gregory Newby
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Patent number: 11957695Abstract: The subject matter disclosed herein is generally directed to modulating T cell dysfunctional and effector states by modulating glucocorticoid and IL-27 signaling. The invention further relates to modulating immune states, such as CD8 T cell immune states, in vivo, ex vivo and in vitro. The invention further relates to diagnostic and screening methods.Type: GrantFiled: April 26, 2019Date of Patent: April 16, 2024Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, The Brigham and Women's Hospital, Inc.Inventors: Ana Carrizosa Anderson, Asaf Madi, Nandini Acharya, Vijay K. Kuchroo, Aviv Regev
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Publication number: 20240117365Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.Type: ApplicationFiled: August 23, 2023Publication date: April 11, 2024Applicants: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventor: Feng Zhang
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Publication number: 20240117440Abstract: The invention provides a molecular classifier and a targeted sequencing assay for use in characterization and treatment of diffuse large B-cell lymphoma.Type: ApplicationFiled: September 15, 2023Publication date: April 11, 2024Applicants: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., The General Hospital CorporationInventors: Bjoern CHAPUY, Donald STEWART, Tim WOOD, Margaret SHIPP, Gad GETZ, Mark MURAKAMI, Lee LAWTON, Andrew DUNFORD, Kirsty WIENAND
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Publication number: 20240110238Abstract: As described below, disclosed herein are methods of analyzing DNA methylation in cell-free DNA (cfDNA) and genomic DNA (gDNA) from sequencing data.Type: ApplicationFiled: September 8, 2023Publication date: April 4, 2024Applicants: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Yaping LIU, Manolis KELLIS, Viktor ADALSTEINSSON, Zhizhuo ZHANG
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Publication number: 20240108755Abstract: The invention features compositions and methods for treating developmental, neurodevelopmental (e.g., Fragile X syndrome (FXS)) or Down syndrome (DS) or neurodegenerative disorders (e.g., Alzheimer's disease (AD)) by increasing expression of Fragile X Mental Retardation Protein (FMRP) in patients having such disorders.Type: ApplicationFiled: September 22, 2023Publication date: April 4, 2024Applicant: The Broad Institute, Inc.Inventors: Lindy BARRETT, Sara G. SUSCO
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Publication number: 20240110223Abstract: Methods and kits are disclosed related to preparing a nucleic acid sample for sequencing that minimizes propagation of false mutations due to amplification of nucleotide damage or alterations confined to one strand wherein at least a portion of the sample is double-stranded.Type: ApplicationFiled: December 10, 2021Publication date: April 4, 2024Applicant: The Broad Institute, Inc.Inventors: Viktor A. Adalsteinsson, Kan Xiong, Douglas Shea, Justin Rhoades
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Publication number: 20240109850Abstract: The present invention includes compounds of formula (I) and methods for its preparation and treatment of disorders with activated peroxisome preoliferator-activated receptor gamma (PPARG), particularly cancer.Type: ApplicationFiled: August 31, 2023Publication date: April 4, 2024Applicants: Bayer Aktiengesellschaft, The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc.Inventors: Knut EIS, Elisabeth POOK, Ulf BRÜGGEMEIER, Adelaide Clara F. A. DE LEMOS, Sven CHRISTIAN, Isabel Sophie JERCHEL-FURAU, Ulrike RAUH, Nico BRÄUER, Timo STELLFELD, Anders Roland FRIBERG, Christian LECHNER, Stefan KAULFUSS, Hanna MEYER, Charlotte Christine KOPITZ, Steven James FERRARA, Jonathan GOLDSTEIN, Matthew MEYERSON, Christopher LEMKE, Timothy A. LEWIS
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Publication number: 20240093193Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are stmctural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formulation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems.Type: ApplicationFiled: August 15, 2023Publication date: March 21, 2024Applicants: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Feng ZHANG, Silvana Konermann, James Dahlman, Omar Abudayyeh
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Publication number: 20240084286Abstract: This disclosure provides a method for substantially increasing the concentration of cfDNA in a patient. By injecting a patient with lipid and/or polymer nanoparticles, agents that bind cfDNA, or inhibit deoxyribonucleases prior to collection of a sample of cfDNA, e.g., by way of a liquid biopsy, major pathways for the degradation of cfDNA are temporarily blocked, permitting transient accumulation of cfDNA. This strategy has the potential to dramatically enhance the quality of detection achieved by downstream cfDNA e analytical applications, such as sequencing applications.Type: ApplicationFiled: January 25, 2022Publication date: March 14, 2024Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, The General Hospital CorporationInventors: Viktor A. Adalsteinsson, Shervin Tabrizi, Sangeeta N. Bhatia, J. Christopher Love, Maria Carmen Martin Alonso, Kan Xiong
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Publication number: 20240084364Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.Type: ApplicationFiled: August 17, 2023Publication date: March 14, 2024Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Feng ZHANG, Bernd ZETSCHE, Jonathan S. GOOTENBERG, Omar O. ABUDAYYEH, Ian SLAYMAKER
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Publication number: 20240077502Abstract: Evolved sortases exhibiting enhanced reaction kinetics and/or altered substrate preferences are provided herein, for example evolved sortases that bind recognitions motifs comprising a LMVGG [SEQ ID NO: 3] sequence. Also provided are methods (e.g., orthogonal transpeptidation and diagnostics methods) for using such sortases.Type: ApplicationFiled: January 11, 2022Publication date: March 7, 2024Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, The Brigham and Women's Hospital Inc.Inventors: David R. Liu, Christopher J Podracky, Chihui An, Dominic Walsh
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Patent number: 11920150Abstract: Described herein are targeting moieties that can be capable of specifically targeting muscle cells and can include an n-mer motif. In some embodiments, the n-mer motif contains an RGD motif. Also described herein are vector systems, particles, polypeptides that can encode and/or contain one or more targeting moieties. Also described herein are methods of delivering a cargo to a cell, such as a muscle cell, using one or more of the targeting moieties described herein.Type: GrantFiled: March 29, 2022Date of Patent: March 5, 2024Assignees: The Broad Institute, Inc., President and Fellows of Harvard College, Massachusetts Institute of TechnologyInventors: Pardis Sabeti, Mohammadsharif Tabebordbar, Simon Ye
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Patent number: 11912985Abstract: The present disclosure provides systems, compositions, and methods for simultaneously editing both strands of a double-stranded DNA sequence at a target site to be edited. Further provided herein are pharmaceutical compositions, polynucleotides, vectors, cells, and kits for simultaneously editing both strands of a double-stranded DNA sequence.Type: GrantFiled: November 7, 2022Date of Patent: February 27, 2024Assignees: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone, Jonathan Ma Levy, Xin Gao, Christopher J. Podracky
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Patent number: 11913075Abstract: The subject matter disclosed herein is generally directed to detecting and modulating novel gene signatures for the treatment and prognosis of cancer. The novel gene signatures predict overall survival in cancer and can be targeted therapeutically.Type: GrantFiled: March 30, 2018Date of Patent: February 27, 2024Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, Dana-Farber Cancer Institute, Inc.Inventors: Aviv Regev, Orit Rozenblatt-Rosen, Benjamin Izar, Livnat Jerby, Asaf Rotem
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Patent number: 11913044Abstract: Some aspects of this disclosure relate to strategies, systems, methods, compositions, and kits that are useful for production (e.g., evolution) of cytidine deaminase protein variants that are characterized by increased soluble expression and/or stability relative to the wild-type cytidine deaminase protein from which they are evolved. In some embodiments, evolved cytidine deaminase variants described by the disclosure are useful for incorporation into targeted nucleic acid editing proteins, for example in fusion proteins with a Cas9 domain or variant thereof.Type: GrantFiled: June 14, 2019Date of Patent: February 27, 2024Assignees: President and Fellows of Harvard College, The Broad Institute, Inc.Inventors: David R. Liu, Tina Wang