Patents Assigned to Whitehead Institute for Biomedical Research
  • Patent number: 12215361
    Abstract: The disclosure provides, in various embodiments, fusion proteins comprising a DNA-binding domain, a DNMT3A-binding domain, and a H3K4me0; and polynucleotides and vectors encoding one or more of the fusion proteins. The disclosure also provides, in various embodiments, gene-delivery systems, cells, compositions (e.g., pharmaceutical compositions) and kits comprising one or more of the fusion proteins polynucleotides, or vectors; methods of epigenetically modifying a genomic locus in a cell; and methods of treating a subject (e.g., a human) in need thereof.
    Type: Grant
    Filed: February 16, 2024
    Date of Patent: February 4, 2025
    Assignee: WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH
    Inventors: Edwin Neumann, Tessa Bertozzi, Jonathan Weissman
  • Publication number: 20250032430
    Abstract: Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are methods, uses, and kits involving the disclosed compounds and pharmaceutical compositions thereof for treating and/or preventing a disease (e.g., a metabolic disorder (e.g., obesity, diabetes), a hypoxia related disease (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, neurodegenerative disorder, hypoxia, ischemia, oxidative stress, or a mitochondrial DNA related disorder), or a disease resulting from rhodoquinone depletion (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, metabolic disorder, or neurodegenerative disorder)) in a subject.
    Type: Application
    Filed: November 2, 2022
    Publication date: January 30, 2025
    Applicants: Whitehead Institute for Biomedical Research, University of Massachusetts
    Inventors: David M. Sabatini, Jessica Spinelli
  • Patent number: 12146186
    Abstract: The disclosed Hi-C protocol can identify genomic loci that are spatially co-located in vivo. These spatial co-locations may include, but are not limited to, intrachromosomal interactions and/or interchromosomal interactions. Hi-C techniques may be applied to many different scales of interest. For example, on a large scale, Hi-C techniques can be used to identify long-range interactions between distant genomic loci.
    Type: Grant
    Filed: August 11, 2020
    Date of Patent: November 19, 2024
    Assignees: Presidents and Fellows of Harvard University, Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, University of Massachusetts
    Inventors: Job Dekker, Erez Lieberman Aiden, Nynke Van Berkum, Andreas Gnirke, Eric Lander, Chad Nusbaum, Louise Williams, Alexandre Melnikov, Georgia Giannoukos
  • Patent number: 12123019
    Abstract: The present disclosure provides compounds of any one of Formulae (A) to (L). The present disclosure also provides compositions, uses, and methods that include or involve a compound described herein, a serine/threonine-protein kinase B-Raf (BRAF) inhibitor, an epidermal growth factor receptor (EGFR) inhibitor, a vascular endothelial growth factor 1 (VEGFR1) inhibitor, a fibroblast growth factor receptor 1 (FGFR1) inhibitor, or a combination thereof. The compounds, compositions, uses, and methods are useful in changing the pluripotency state of a vertebrate cell to a more naïve state.
    Type: Grant
    Filed: October 15, 2020
    Date of Patent: October 22, 2024
    Assignees: Whitehead Institute for Biomedical Research, Dana-Farber Cancer Institute, Inc.
    Inventors: Thorold W Theunissen, Nathanael S. Gray, Rudolf Jaenisch
  • Publication number: 20240325575
    Abstract: Provided herein are methods for producing site specific PEG modifications to single domain antibodies (e.g., VHHs). Methods for producing site-specifically conjugated bivalent single domain antibodies (e.g., VHHs) are also provided. Methods for labeling (e.g., with a fluorophore or radionuclide) site-specifically PEGylated single domain antibodies and site-specifically conjugated bivalent single domain antibodies are also provided.
    Type: Application
    Filed: June 7, 2024
    Publication date: October 3, 2024
    Applicant: Whitehead Institute for Biomedical Research
    Inventors: Mohammad Rashidian, Hidde L. Ploegh
  • Publication number: 20240294957
    Abstract: Disclosed are methods, compositions, proteins, nucleic acids, cells, vectors, compounds, reagents, and systems for the preparation of kavalactones, flavokavains, and kavalactone and flavokavain biosynthetic intermediates using enzymes expressed in heterologous host cells, such as microorganisms or plants, or using in vitro enzymatic reactions. This invention also provides for the expression of the enzymes by recombinant cell lines and vectors. Furthermore, the enzymes can be components of constructs such as fusion proteins. The kavalactones produced can be utilized to treat anxiety disorder, insomnia, and other psychological and neurological disorders. The flavokavains produced can be utilized to treat various cancers including colon, bladder, and breast cancers.
    Type: Application
    Filed: July 12, 2023
    Publication date: September 5, 2024
    Applicant: Whitehead Institute for Biomedical Research
    Inventors: Tomás Pluskal, Jing-Ke Weng
  • Publication number: 20240287549
    Abstract: The present disclosure provides, in various aspects, engineered alcohol tolerant yeast and methods of producing high concentrations of biofuels and bioplastics from toxic feedstocks.
    Type: Application
    Filed: June 23, 2022
    Publication date: August 29, 2024
    Applicants: Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research
    Inventors: Felix Lam, Gregory Stephanopoulos, Gerald Fink
  • Patent number: 12068059
    Abstract: Disclosed are methods, systems, cells and compositions directed to modeling a physiologic or pathologic process in an animal using a set of yeast genes analogous to a set of animal genes and augmenting the physiologic or pathologic process in the animal with predicted gene interactions based on the interactions between the set of yeast genes. Also disclosed are methods of screening for and using therapeutics for neurodegenerative proteinopathies.
    Type: Grant
    Filed: January 25, 2018
    Date of Patent: August 20, 2024
    Assignees: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
    Inventors: Vikram Khurana, Chee Yeun Chung, Susan Lindquist, Bonnie A. Berger, Ernest Fraenkel, Jian Peng
  • Patent number: 12060588
    Abstract: The invention relates to methods of modifying DNA methylation by contacting a cell with a catalytically inactive site specific nuclease fused to an effector domain having methylation or demethylation activity and one or more guide sequences.
    Type: Grant
    Filed: July 6, 2022
    Date of Patent: August 13, 2024
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Rudolf Jaenisch, X. Shawn Liu, Hao Wu
  • Patent number: 12053465
    Abstract: Potassium chloride cotransporter-2 (KCC2) plays a critical role in brain function, and deficiency in KCC2 has been linked to neurological diseases, psychiatric disorders, and central nervous system injuries. In particular, Rett syndrome (RTT), a severe neurodevelopmental disorder caused by mutations in the X-linked gene Methyl CpG binding Protein 2 (MECP2), has been linked to deficits in KCC2. The disclosure reports the use of CRISPR/Cas9 genome-editing technology to generate stem cell-derived, genetically defined KCC2 reporter human neurons for large-scale compound screening. This screening platform has been utilized to identify a number of small molecule compounds that are capable of enhancing KCC2 expression in both wild-type and RTT neurons, as well as organotypical brain slices cultured from wild-type mice.
    Type: Grant
    Filed: April 5, 2022
    Date of Patent: August 6, 2024
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Rudolf Jaenisch, Xin Tang
  • Patent number: 12048753
    Abstract: Provided herein are methods for producing site specific PEG modifications to single domain antibodies (e.g., VHHs). Methods for producing site-specifically conjugated bivalent single domain antibodies (e.g., VHHs) are also provided. Methods for labeling (e.g., with a fluorophore or radionuclide) site-specifically PEGylated single domain antibodies and site-specifically conjugated bivalent single domain antibodies are also provided.
    Type: Grant
    Filed: October 1, 2016
    Date of Patent: July 30, 2024
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Mohammad Rashidian, Hidde L. Ploegh
  • Publication number: 20240249796
    Abstract: Work described herein reveals 3D regulatory landscapes of hESCs representative of early human development. This work also demonstrates that cohesin-associated CTCF loops, and the cohesin-associate enhancer-promoter loops within them, dominate the organization of TADs. The CTCF-CTCF loops form a chromosomal scaffold of insulated neighborhoods that are largely preserved in vertebrates, and enhancer-promoter interactions occur within these neighborhoods. Genes are regulated in the context of conserved insulated neighborhood structures. Loss of neighborhood structures occurs frequently in cancer cells, and proto-oncogenes can be activated by genetic alterations that disrupt specific 3D chromosome structures.
    Type: Application
    Filed: November 2, 2023
    Publication date: July 25, 2024
    Applicant: Whitehead Institute for Biomedical Research
    Inventors: Denes Hnisz, Richard A. Young, Diego R. Borges-Rivera, Abraham S. Weintraub, Xiong Ji, Daniel B. Dadon, Zi Peng Fan, Tong Ihn Lee
  • Patent number: 11992505
    Abstract: Methods for the in vitro production of enucleated red blood cells and the enucleated red blood cells thus prepared are provided. Such enucleated red blood cells may express a sortaggable surface protein, which allows for surface modification in the presence of a sortase. Also described herein are surface modified enucleated red blood cells, e.g., conjugated with an agent of interest such as a peptide, a detectable label, or a chemotherapeutic agent, and uses thereof in delivering the agent to a subject.
    Type: Grant
    Filed: September 16, 2019
    Date of Patent: May 28, 2024
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Harvey Lodish, Hidde L. Ploegh, Hsiang-Ying Lee, Jiahai Shi, Lenka Hoffman, Novalia Pishesha
  • Patent number: 11987815
    Abstract: The invention provides methods for reprogramming somatic cells to generate multipotent or pluripotent cells. Such methods are useful for a variety of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a less differentiated state.
    Type: Grant
    Filed: October 28, 2019
    Date of Patent: May 21, 2024
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Rudolf Jaenisch, Konrad Hochedlinger
  • Patent number: 11945845
    Abstract: The present disclosure provides genetically altered protozoan parasites comprising a mutation in a bradyzoite formation deficient 1 (BFD1) gene, wherein the mutation inhibits differentiation of the parasite into a bradyzoite. The genetically altered protozoan parasites can be utilized in vaccine compositions and in methods of treating apicomplexan parasite infection.
    Type: Grant
    Filed: May 30, 2020
    Date of Patent: April 2, 2024
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Ben Waldman, Sebastian Lourido
  • Patent number: 11873496
    Abstract: The invention relates to methods of modulating the expression of one or more genes in a cell by modulating the multimerization of a transcription factor and/or modulating the formation of enhancer-promoter DNA loops, and thereby modulating the expression of the one or more genes. The invention also relates to treating diseases and conditions involving aberrant gene expression by modulating the multimerization of a transcription factor and/or modulating the formation of enhancer-promoter DNA loops. The invention also relates to methods for screening for compounds that modulate expression of one or more genes in a cell.
    Type: Grant
    Filed: January 9, 2018
    Date of Patent: January 16, 2024
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Richard A. Young, Abraham S. Weintraub, Charles H. Li, Alla A. Sigova
  • Patent number: 11850216
    Abstract: The present invention, in some aspects, provides methods, reagents, compositions, and kits for the radiolabeling of proteins, for example, of proteins useful for positron emission tomography (PET) or single-photon emission computed tomography (SPECT) (e.g., for diagnostic and therapeutic applications), using sortase-mediated transpeptidation reactions. Some aspects of this invention provide methods for the conjugation of an agent, for example, a radioactive agent or molecule to diagnostic or therapeutic peptides or proteins. Compositions comprising sortagged, radiolabeled proteins as well as reagents for generating radiolabeled proteins are also provided. Kits comprising reagents useful for the generation of radiolabeled proteins are provided, as are precursor proteins that comprise a sortase recognition motif.
    Type: Grant
    Filed: January 8, 2020
    Date of Patent: December 26, 2023
    Assignees: Whitehead Institute for Biomedical Research, The General Hospital Corporation
    Inventors: Mohammad Rashidian, Hidde L. Ploegh, Ralph Weissleder, Edmund J. Keliher
  • Patent number: 11851670
    Abstract: The disclosure relates to a method of reprogramming one or more somatic cells, e.g., partially differentiated or fully/terminally differentiated somatic cells, to a less differentiated state, e.g., a pluripotent or multipotent state. In further embodiments the invention also relates to reprogrammed somatic cells produced by methods of the invention, to chimeric animals comprising reprogrammed somatic cells of the invention, to uses of said cells, and to methods for identifying agents useful for reprogramming somatic cells.
    Type: Grant
    Filed: June 11, 2019
    Date of Patent: December 26, 2023
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Rudolf Jaenisch, Bryce Woodbury Carey, Yaqub Hanna
  • Publication number: 20230348605
    Abstract: Methods for developing disease-related nanobodies and related products and kits are provided. The disease-specific proteins are extracellular matrix (ECM) proteins, domains or epitopes that are associated with various aspects of disease and are not present, or are present in very low quantities, in non-diseased individuals. Highly effective nanobodies capable of specifically binding to these ECM protein epitopes useful in in vivo imaging assays, the detection, diagnosis and treatment of diseases as well as monitoring therapeutic progress in a patient with a disease are provided herein.
    Type: Application
    Filed: February 28, 2023
    Publication date: November 2, 2023
    Applicants: Massachusetts Institute of Technology, Children's Medical Center Corporation, Whitehead Institute for Biomedical Research
    Inventors: Richard O. Hynes, Noor Jailkhani, Hidde L. Ploegh, Yushu J. Xie
  • Patent number: 11746364
    Abstract: Disclosed are methods, compositions, proteins, nucleic acids, cells, vectors, compounds, reagents, and systems for the preparation of kavalactones, flavokavains, and kavalactone and flavokavain biosynthetic intermediates using enzymes expressed in heterologous host cells, such as microorganisms or plants, or using in vitro enzymatic reactions. This invention also provides for the expression of the enzymes by recombinant cell lines and vectors. Furthermore, the enzymes can be components of constructs such as fusion proteins. The kavalactones produced can be utilized to treat anxiety disorder, insomnia, and other psychological and neurological disorders. The flavokavains produced can be utilized to treat various cancers including colon, bladder, and breast cancers.
    Type: Grant
    Filed: March 3, 2021
    Date of Patent: September 5, 2023
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Tomás Pluskal, Jing-Ke Weng