Patents Assigned to Whitehead Institute for Biomedical Research
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Patent number: 12215361Abstract: 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: GrantFiled: February 16, 2024Date of Patent: February 4, 2025Assignee: WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCHInventors: Edwin Neumann, Tessa Bertozzi, Jonathan Weissman
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Publication number: 20250032430Abstract: 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: ApplicationFiled: November 2, 2022Publication date: January 30, 2025Applicants: Whitehead Institute for Biomedical Research, University of MassachusettsInventors: David M. Sabatini, Jessica Spinelli
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Patent number: 12146186Abstract: 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: GrantFiled: August 11, 2020Date of Patent: November 19, 2024Assignees: Presidents and Fellows of Harvard University, Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, University of MassachusettsInventors: Job Dekker, Erez Lieberman Aiden, Nynke Van Berkum, Andreas Gnirke, Eric Lander, Chad Nusbaum, Louise Williams, Alexandre Melnikov, Georgia Giannoukos
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Patent number: 12123019Abstract: 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: GrantFiled: October 15, 2020Date of Patent: October 22, 2024Assignees: Whitehead Institute for Biomedical Research, Dana-Farber Cancer Institute, Inc.Inventors: Thorold W Theunissen, Nathanael S. Gray, Rudolf Jaenisch
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Publication number: 20240325575Abstract: 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: ApplicationFiled: June 7, 2024Publication date: October 3, 2024Applicant: Whitehead Institute for Biomedical ResearchInventors: Mohammad Rashidian, Hidde L. Ploegh
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Publication number: 20240294957Abstract: 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: ApplicationFiled: July 12, 2023Publication date: September 5, 2024Applicant: Whitehead Institute for Biomedical ResearchInventors: Tomás Pluskal, Jing-Ke Weng
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Publication number: 20240287549Abstract: 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: ApplicationFiled: June 23, 2022Publication date: August 29, 2024Applicants: Massachusetts Institute of Technology, Whitehead Institute for Biomedical ResearchInventors: Felix Lam, Gregory Stephanopoulos, Gerald Fink
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Patent number: 12068059Abstract: 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: GrantFiled: January 25, 2018Date of Patent: August 20, 2024Assignees: Whitehead Institute for Biomedical Research, Massachusetts Institute of TechnologyInventors: Vikram Khurana, Chee Yeun Chung, Susan Lindquist, Bonnie A. Berger, Ernest Fraenkel, Jian Peng
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Patent number: 12060588Abstract: 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: GrantFiled: July 6, 2022Date of Patent: August 13, 2024Assignee: Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, X. Shawn Liu, Hao Wu
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Patent number: 12053465Abstract: 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: GrantFiled: April 5, 2022Date of Patent: August 6, 2024Assignee: Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, Xin Tang
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Patent number: 12048753Abstract: 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: GrantFiled: October 1, 2016Date of Patent: July 30, 2024Assignee: Whitehead Institute for Biomedical ResearchInventors: Mohammad Rashidian, Hidde L. Ploegh
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Publication number: 20240249796Abstract: 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: ApplicationFiled: November 2, 2023Publication date: July 25, 2024Applicant: Whitehead Institute for Biomedical ResearchInventors: Denes Hnisz, Richard A. Young, Diego R. Borges-Rivera, Abraham S. Weintraub, Xiong Ji, Daniel B. Dadon, Zi Peng Fan, Tong Ihn Lee
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Patent number: 11992505Abstract: 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: GrantFiled: September 16, 2019Date of Patent: May 28, 2024Assignee: Whitehead Institute for Biomedical ResearchInventors: Harvey Lodish, Hidde L. Ploegh, Hsiang-Ying Lee, Jiahai Shi, Lenka Hoffman, Novalia Pishesha
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Patent number: 11987815Abstract: 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: GrantFiled: October 28, 2019Date of Patent: May 21, 2024Assignee: Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, Konrad Hochedlinger
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Patent number: 11945845Abstract: 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: GrantFiled: May 30, 2020Date of Patent: April 2, 2024Assignee: Whitehead Institute for Biomedical ResearchInventors: Ben Waldman, Sebastian Lourido
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Patent number: 11873496Abstract: 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: GrantFiled: January 9, 2018Date of Patent: January 16, 2024Assignee: Whitehead Institute for Biomedical ResearchInventors: Richard A. Young, Abraham S. Weintraub, Charles H. Li, Alla A. Sigova
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Patent number: 11850216Abstract: 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: GrantFiled: January 8, 2020Date of Patent: December 26, 2023Assignees: Whitehead Institute for Biomedical Research, The General Hospital CorporationInventors: Mohammad Rashidian, Hidde L. Ploegh, Ralph Weissleder, Edmund J. Keliher
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Patent number: 11851670Abstract: 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: GrantFiled: June 11, 2019Date of Patent: December 26, 2023Assignee: Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, Bryce Woodbury Carey, Yaqub Hanna
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Publication number: 20230348605Abstract: 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: ApplicationFiled: February 28, 2023Publication date: November 2, 2023Applicants: Massachusetts Institute of Technology, Children's Medical Center Corporation, Whitehead Institute for Biomedical ResearchInventors: Richard O. Hynes, Noor Jailkhani, Hidde L. Ploegh, Yushu J. Xie
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Patent number: 11746364Abstract: 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: GrantFiled: March 3, 2021Date of Patent: September 5, 2023Assignee: Whitehead Institute for Biomedical ResearchInventors: Tomás Pluskal, Jing-Ke Weng