Patents Assigned to THE BROAD INSTITUTE, INC.
  • Patent number: 11987795
    Abstract: Described are methods for enhancing exon skipping in a pre-mRNA of interest, comprising contacting the pre-mRNA with interfering oligonucleotides such as antisense, siRNA, and miRNA. The exon skipping methods are associated with methods of treating a variety of diseases and conditions, including cancer.
    Type: Grant
    Filed: September 22, 2021
    Date of Patent: May 21, 2024
    Assignees: The Broad Institute, Inc., The General Hospital Corporation
    Inventors: Vamsi Krishna Mootha, Alexis André Jourdain
  • Publication number: 20240158810
    Abstract: The disclosure features compositions and methods for ameliorating cognitive impairments associated with neuropsychiatric disorders, particularly those associated with anterodorsal (AD) thalamus hyperexcitability in the brain of a subject. Various embodiments of the disclosure provide for personalized and targeted therapeutic approaches for screening, diagnosing, preventing, and treating cognitive impairments and neuropsychiatric disorders.
    Type: Application
    Filed: December 22, 2023
    Publication date: May 16, 2024
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Guoping FENG, Dheeraj ROY, Ying ZHANG
  • Publication number: 20240158779
    Abstract: 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. In some aspects, the systems comprise a first and second prime editor complex, wherein each of the first and second prime editor complexes comprises (1) a prime editor comprising (i) a nucleic acid programmable DNA binding protein (napDNAbp), and (ii) a polypeptide having an RNA-dependent DNA polymerase activity; and (2) a pegRNA comprising a spacer sequence, gRNA core, a DNA synthesis template, and a primer binding site, wherein the DNA synthesis template encodes a desired DNA sequence or a complement thereof, wherein the desired DNA sequence and the complement thereof form a duplex comprising an edited portion which integrates into the target site to be edited. In some aspects, the systems comprise a first, second, third, and fourth prime editor complex, each comprising a prime editor and a PEgRNA.
    Type: Application
    Filed: December 8, 2023
    Publication date: May 16, 2024
    Applicants: The Broad Institute, Inc., President and Fellows of Harvard College
    Inventors: David R. Liu, Andrew Vito Anzalone, Jonathan Ma Levy, Xin Gao, Christopher J. Podracky
  • Publication number: 20240150277
    Abstract: 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: Application
    Filed: August 31, 2023
    Publication date: May 9, 2024
    Applicants: 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
  • Publication number: 20240144704
    Abstract: 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: Application
    Filed: February 18, 2022
    Publication date: May 2, 2024
    Applicants: c/o The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College
    Inventors: Xiao Wang, Jia Liu, Yichun He
  • Patent number: 11965159
    Abstract: 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: Grant
    Filed: January 29, 2020
    Date of Patent: April 23, 2024
    Assignees: The Broad Institute, Inc., The Brigham and Women's Hospital, Inc., The Regents of the University of California
    Inventors: Amit Choudhary, Kurt Cox, Hari Subramanian, Elisa Franco
  • Publication number: 20240124924
    Abstract: 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: Application
    Filed: February 22, 2022
    Publication date: April 18, 2024
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, THE GENERAL HOSPITAL CORPORATION
    Inventors: Aziz Al'Khafaji, Frances Keer, Paul Blainey, Nir Hacohen
  • Publication number: 20240124866
    Abstract: 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: Application
    Filed: September 1, 2023
    Publication date: April 18, 2024
    Applicants: 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
  • Patent number: 11957695
    Abstract: 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: Grant
    Filed: April 26, 2019
    Date of Patent: April 16, 2024
    Assignees: 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
  • Publication number: 20240117365
    Abstract: 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: Application
    Filed: August 23, 2023
    Publication date: April 11, 2024
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventor: Feng Zhang
  • Publication number: 20240117440
    Abstract: The invention provides a molecular classifier and a targeted sequencing assay for use in characterization and treatment of diffuse large B-cell lymphoma.
    Type: Application
    Filed: September 15, 2023
    Publication date: April 11, 2024
    Applicants: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., The General Hospital Corporation
    Inventors: Bjoern CHAPUY, Donald STEWART, Tim WOOD, Margaret SHIPP, Gad GETZ, Mark MURAKAMI, Lee LAWTON, Andrew DUNFORD, Kirsty WIENAND
  • Publication number: 20240110238
    Abstract: As described below, disclosed herein are methods of analyzing DNA methylation in cell-free DNA (cfDNA) and genomic DNA (gDNA) from sequencing data.
    Type: Application
    Filed: September 8, 2023
    Publication date: April 4, 2024
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Yaping LIU, Manolis KELLIS, Viktor ADALSTEINSSON, Zhizhuo ZHANG
  • Publication number: 20240108755
    Abstract: 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: Application
    Filed: September 22, 2023
    Publication date: April 4, 2024
    Applicant: The Broad Institute, Inc.
    Inventors: Lindy BARRETT, Sara G. SUSCO
  • Publication number: 20240109850
    Abstract: 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: Application
    Filed: August 31, 2023
    Publication date: April 4, 2024
    Applicants: 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
  • Publication number: 20240110223
    Abstract: 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: Application
    Filed: December 10, 2021
    Publication date: April 4, 2024
    Applicant: The Broad Institute, Inc.
    Inventors: Viktor A. Adalsteinsson, Kan Xiong, Douglas Shea, Justin Rhoades
  • Publication number: 20240093193
    Abstract: 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: Application
    Filed: August 15, 2023
    Publication date: March 21, 2024
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Feng ZHANG, Silvana Konermann, James Dahlman, Omar Abudayyeh
  • Publication number: 20240084286
    Abstract: 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: Application
    Filed: January 25, 2022
    Publication date: March 14, 2024
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, The General Hospital Corporation
    Inventors: Viktor A. Adalsteinsson, Shervin Tabrizi, Sangeeta N. Bhatia, J. Christopher Love, Maria Carmen Martin Alonso, Kan Xiong
  • Publication number: 20240084364
    Abstract: 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: Application
    Filed: August 17, 2023
    Publication date: March 14, 2024
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College
    Inventors: Feng ZHANG, Bernd ZETSCHE, Jonathan S. GOOTENBERG, Omar O. ABUDAYYEH, Ian SLAYMAKER
  • Publication number: 20240077502
    Abstract: 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: Application
    Filed: January 11, 2022
    Publication date: March 7, 2024
    Applicants: 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
  • Patent number: 11920150
    Abstract: 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: Grant
    Filed: March 29, 2022
    Date of Patent: March 5, 2024
    Assignees: The Broad Institute, Inc., President and Fellows of Harvard College, Massachusetts Institute of Technology
    Inventors: Pardis Sabeti, Mohammadsharif Tabebordbar, Simon Ye