Patents Assigned to BROAD INSTITUTE
  • Engineering and optimization of systems, methods, enzymes and guide scaffolds of CAS9 orthologs and variants for sequence manipulation
    Patent number: 11578312
    Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural 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 formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems. In particular the present invention comprehends engineered new guide architectures and enzymes to be used in optimized Staphylococcus aureus CRISPR-Cas enzyme systems.
    Type: Grant
    Filed: December 12, 2017
    Date of Patent: February 14, 2023
    Assignees: THE BROAD INSTITUTE INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE, UNIVERSITY OF TOKYO
    Inventors: Feng Zhang, Winston Yan, Osamu Nureki, Kaijie Zheng, Le Cong, Hiroshi Nishimasu, Fei Ran, Yinqing Li
  • RETROTRANSPOSONS AND USE THEREOF
    Publication number: 20230040216
    Abstract: Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems and non-LTR retrotransposon elements.
    Type: Application
    Filed: November 18, 2020
    Publication date: February 9, 2023
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Michael Segel, Alim Ladha
  • PROGRAMMABLE DNA NUCLEASE-ASSOCIATED LIGASE AND METHODS OF USE THEREOF
    Publication number: 20230037794
    Abstract: Described in certain exemplary embodiments herein are programmable DNA nuclease systems and/or components thereof that include or are otherwise associated with a ligase. Also described in certain exemplary embodiments herein are method of using the DNA nuclease systems described herein to modify a nucleic acid sequence.
    Type: Application
    Filed: December 23, 2020
    Publication date: February 9, 2023
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Han Altae-Tran
  • Targeting BCL11A enhancer functional regions for fetal hemoglobin reinduction
    Patent number: 11572543
    Abstract: Provided herein are nucleic acid molecules that target the BCL11A enhancer functional regions, compositions comprising the nucleic acid molecules and methods for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels. In particular, the nucleic acid molecules target the +62, +58, and/or the +55 enhancer functional regions.
    Type: Grant
    Filed: May 6, 2016
    Date of Patent: February 7, 2023
    Assignees: THE CHILDREN'S MEDICAL CENTER. CORPORATION, THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Daniel E. Bauer, Stuart H. Orkin, Neville Sanjana, Ophir Shalem, Feng Zhang
  • Compositions and methods for combinatorial drug discovery in nanoliter droplets
    Patent number: 11564970
    Abstract: Compositions and methods for combinatorial drug discovery in nanoliter droplets are described. Novel synergistic agents that increase efficacy of antibiotic agents to treat bacterial infection are disclosed.
    Type: Grant
    Filed: October 9, 2018
    Date of Patent: January 31, 2023
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Paul Blainey, Anthony Kulesa, Jared Kehe
  • SUBSTITUTED HYDANTOINAMIDES AS ADAMTS7 ANTAGONISTS
    Publication number: 20230027346
    Abstract: The application relates to substituted hydantoinamides of formula (I) as ADAMTS7 antagonists, to processes for their preparation, their use alone or in combination for the treatment or prophylaxis of diseases, in particular of cardiovascular diseases, including atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), arterial occlusive disease or restenosis after angioplasty. R1 is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, heteroaryl or phenyl; R2 is hydrogen, cyano, halogen, alkylsulfonyl, alkyl, cycloalkyl or alkoxy; R3, R4, R5, R6, R7 and R8 are independently hydrogen, halogen, alkyl or alkoxy; most groups being optionally substituted; with the proviso that at least one of R2, R3, R4 is H; X1, X2, X3, X4, X5 and X6 are independently N or C; with the proviso that in each ring maximal one X is N.
    Type: Application
    Filed: November 12, 2020
    Publication date: January 26, 2023
    Applicants: BAYER AKTIENGESELLSCHAFT, THE BROAD INSTITUTE, INC.
    Inventors: Daniel MEIBOM, Yolanda CANCHO GRANDE, Pierre WASNAIRE, Sarah Anna Liesa JOHANNES, Kristin BEYER, Till FREUDENBERGER, Damian BROCKSCHNIEDER, Dmitry ZUBOV, Dzianis MENSHYKAU, Tanja KRAINZ, Bryan MACDONALD, Yi XING, Nadine ELOWE, Guzman SANCHEZ
  • NOVEL TYPE VI CRISPR ENZYMES AND SYSTEMS
    Publication number: 20230025039
    Abstract: The present disclosure provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides Cas proteins and their use in modifying target sequences.
    Type: Application
    Filed: September 18, 2020
    Publication date: January 26, 2023
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Han Altae-Tran, Soumya Kannan
  • Oligonucleotide-coupled antibodies for single cell or single complex protein measurements
    Patent number: 11549135
    Abstract: Provided herein are compositions and methods for simultaneously measuring target oligonucleotides and protein in single cells. Compositions comprise an antibody-tagged oligonucleotide, including an origin specific barcode handle sequence, a first primer handle sequence, a second primer handle sequence, and a target binding region. The composition may also include an adapter sequence, a unique molecular identifier (UMI), and a poly-A sequence. Methods for simultaneously measuring target oligonucleotides and protein in single cells generally involve delivering a mixture of the composition to a population of cells and encapsulating individual cells in an individual discrete volume comprising PCR primers on a bead.
    Type: Grant
    Filed: September 13, 2019
    Date of Patent: January 10, 2023
    Assignees: THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventor: Jesse Engreitz
  • Methods and compositions for studying cell evolution
    Patent number: 11547614
    Abstract: The subject matter disclosed herein is generally directed to methods and compositions for tagging cells of interest, tracking evolution of the tagged cells, and recovering the original tagged cells for further study. Specifically, cells are tagged with a DNA construct encoding a barcode sequence comprising a guide sequence. Barcoded cells can then be recovered using a reporter construct having CRISPR target sequences specific for the cell having a barcode of interest.
    Type: Grant
    Filed: October 31, 2018
    Date of Patent: January 10, 2023
    Assignees: THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Pratiti Bandopadhayay, Rameen Beroukhim, Paul Blainey, David Feldman, Cory Johannessen, Funien Tsai
  • COMPOSITIONS, METHODS AND USES FOR FREE FATTY ACID SCREENING OF CELLS AT SCALE
    Publication number: 20220404336
    Abstract: The present disclosure relates to compositions and methods for the preparation and use of free fatty acids as crystals and in solution, optionally in array format, for assay of lipotoxicity and related effects (in certain cases, indicators of diseases or disorders, such as type II diabetes) in contacted cells. Identification and therapeutic targeting of high-value gene targets discovered via joint assessment of lipotoxicity/transcriptome data and genetic association study data are also provided.
    Type: Application
    Filed: September 9, 2020
    Publication date: December 22, 2022
    Applicants: THE BROAD INSTITUTE, INC., THE BRIGHAM & WOMEN'S HOSPITAL, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Anna Greka, Nicolas Wieder, Juliana Coraor
  • SMALL TYPE II CAS PROTEINS AND METHODS OF USE THEREOF
    Publication number: 20220403357
    Abstract: The present disclosure provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides small Cas proteins and their use in modifying target sequences. In one aspect, the present disclosure provides a non-naturally occurring or engineered system comprising: a Cas protein that comprises a RuvC domain and a HNH domain, and is less than 850 amino acids in size; and a guide sequence capable of forming a complex with the Cas protein and directing the complex to bind to a target sequence.
    Type: Application
    Filed: November 12, 2020
    Publication date: December 22, 2022
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Soumya Kannan, Han Altae-Tran
  • COMPOSITIONS AND METHODS FOR DELIVERING CARGO TO A TARGET CELL
    Publication number: 20220389451
    Abstract: Provided herein are compositions, systems, and methods for delivering cargo to a target cell. The compositions, systems, and methods comprise one or more polynucleotides encoding one or more endogenous retroviral elements for forming a delivery vesicle and one or more capture moieties for packaging a cargo within the delivery vesicle. The one or more endogenous retroviral elements for forming a delivery vesicle may comprise two or more of a retroviral gag protein, a retroviral envelope protein, a retroviral reverse transcriptase or a combination thereof. The retroviral gag protein alone, the retroviral envelope protein alone, or both the retroviral gag protein and retroviral envelope protein may be endogenous.
    Type: Application
    Filed: September 18, 2020
    Publication date: December 8, 2022
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Michael Segel
  • CRISPR-RELATED METHODS AND COMPOSITIONS WITH GOVERNING gRNAS
    Publication number: 20220389460
    Abstract: Disclosed herein are methods and compositions useful in targeting a payload to, or editing a target nucleic acid, where a governing gRNA molecule is used to target, optionally inactivate, a Cas9 molecule or a Cas9 molecule/gRNA complex.
    Type: Application
    Filed: June 14, 2022
    Publication date: December 8, 2022
    Applicants: EDITAS MEDICINE, INC., THE BROAD INSTITUTE INC., THE UNIVERSITY OF IOWA RESEARCH FOUNDATION, MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng ZHANG, Deborah PALESTRANT, Beverly DAVIDSON, Jordi MATA-FINK, Edgardo RODRIGUEZ, Alexis BORISY
  • NON-NATURALLY OCCURRING CAPSIDS FOR DELIVERY OF NUCLEIC ACIDS AND/OR PROTEINS
    Publication number: 20220389062
    Abstract: Provided herein are non-naturally occurring self-assembling polypeptides for transferring nucleic acids and/or proteins to a cell, pharmaceutical compositions comprising such polypeptides, and methods for treatment comprising use of such compositions. The methods for producing polypeptide compositions may include combining in a solution, unassembled recombinant GAG-like proteins, nucleic acids and/or proteins in low salt conditions; and increasing the ionic strength of the solution.
    Type: Application
    Filed: February 25, 2022
    Publication date: December 8, 2022
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Serge Gueroussov
  • HIGH-RESOLUTION SPATIAL AND QUANTITATIVE DNA ASSESSMENT
    Publication number: 20220389409
    Abstract: The present disclosure relates to compositions and methods for assessing relative DNA levels (e.g., levels of genomic DNA, mtDNA, viral DNA, bacterial DNA, etc.) in a spatially-defined manner across a tissue sample, specifically providing DNA sequence identity and relative abundance information at high-resolution across multiple locations assessed across the tissue sample.
    Type: Application
    Filed: November 9, 2020
    Publication date: December 8, 2022
    Applicants: THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE, THE GENERAL HOSPITAL CORPORATION
    Inventors: Tongtong Zhao, Fei Chen, Jason Buenrostro, Evan Macosko
  • TYPE I-B CRISPR-ASSOCIATED TRANSPOSASE SYSTEMS
    Publication number: 20220380758
    Abstract: Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems and transposable elements.
    Type: Application
    Filed: October 30, 2020
    Publication date: December 1, 2022
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Makoto Saito, Feng Zhang, Guilhem Faure
  • NOVEL CRISPR ENZYMES AND SYSTEMS
    Publication number: 20220364071
    Abstract: The present disclosure provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides mutated Cas13 proteins and their use in modifying target sequences as well as mutated Cas13 nucleic acid sequences and vectors encoding mutated Cas13 proteins and vector systems or CRISPR-Cas13 systems.
    Type: Application
    Filed: July 31, 2019
    Publication date: November 17, 2022
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Ian Slaymaker, Soumya Kannan, Jonathan Gootenberg, Omar Abudayyeh
  • Compositions and methods for targeting cancer-specific sequence variations
    Patent number: 11492670
    Abstract: The present invention relates to compositions and methods for targeting cancer-specific DNA sequences, such as copy number amplifications and other types of cancer-specific sequence variations, such as cancer-specific polymorphisms, insertions, or deletions. The present invention provides hereto sequence-specific DNA targeting agents targeting a sequence within the amplified DNA region or a sequence otherwise specific for a cancer cell compared to a non-cancer cell. The invention further relates to methods for treating cancer, comprising administering such sequence-specific DNA targeting agents. The invention further relates to methods for preparing sequence-specific DNA targeting agent, as well as screening methods using the DNA targeting agents.
    Type: Grant
    Filed: October 20, 2016
    Date of Patent: November 8, 2022
    Assignees: THE BROAD INSTITUTE INC., DANA-FARBER CANCER INSTITUTE, INC., INSTITUTO CARLOS SLIM DE LA SALUD, A.C.
    Inventors: William C. Hahn, Andrew Aguirre, April Cook, Glenn Cowley, Robin Meyers, David E. Root, Aviad Tsherniak, Barbara Weir, Francisca Vazquez
  • RAPID PREDICTION OF DRUG RESPONSIVENESS
    Publication number: 20220340976
    Abstract: The present disclosure relates to compositions and methods for rapid prediction, based upon early single cell transcriptomic assessment of a biopsied sample obtained from a subject, of whether a subject will be responsive to a drug.
    Type: Application
    Filed: September 1, 2020
    Publication date: October 27, 2022
    Applicants: THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Andrew J. Aguirre, Francisca Vazquez, Aviad Tsherniak, James McFarland, Brenton Paolella
  • PROGRAMMABLE POLYNUCLEOTIDE EDITORS FOR ENHANCED HOMOLOGOUS RECOMBINATION
    Publication number: 20220340936
    Abstract: An engineered system for modulating a nucleic acid molecule. In some examples, the system comprises a programmable inducer of DNA damage; one or more functional domain such as a reverse transcriptase domain, topoisomerase domain and/or polymerase domain; a recombination enhancer domain; and an RNA template encoding a donor polynucleotide and capable of forming a complex with the RT domain.
    Type: Application
    Filed: September 28, 2020
    Publication date: October 27, 2022
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Jonathan Schmid-Burgk, Suchita Nety