Patents Assigned to Whitehead Institute
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Patent number: 9532997Abstract: Disclosed herein are novel methods and compositions useful for promoting intestinal stem cell function. The methods and compositions are particularly useful for stimulating the proliferation of and/or self-renewal of intestinal stem cells, as well as for minimizing, preventing, or ameliorating cellular damage resulting from incidental or accidental exposure to radiation (e.g., cancer radiation therapy).Type: GrantFiled: April 3, 2013Date of Patent: January 3, 2017Assignee: Whitehead Institute for Biomedical ResearchInventors: Pekka Katajisto, Michael Pacold, David M. Sabatini, Omer Yilmaz
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Patent number: 9505735Abstract: The present invention provides compounds of Formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting fungal or parasitic growth. The compounds are useful as inhibitors of glycosylphosphatidylinositol (GPI)-anchor biosynthesis, in particular, as inhibitors of fungal Gwt1 activity. The present invention further provides methods of using the compounds described herein for treating fungal or parasitic infections. The compounds can also be used as biological probes to study the effects of inhibiting Gwt1 activity.Type: GrantFiled: June 21, 2013Date of Patent: November 29, 2016Assignees: Whitehead Institute for Biomedical Research, The General Hospital CorporationInventors: Catherine McLellan, Ralph Mazitschek, Luke Whitesell, Susan L. Lindquist
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Patent number: 9497943Abstract: 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 15, 2009Date of Patent: November 22, 2016Assignee: Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, Bryce Woodbury Carey
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Patent number: 9493775Abstract: In some aspects, methods of inhibiting survival or proliferation of a tumor cell are provided, the methods comprising inhibiting the glycine cleavage system (GCS) of the tumor cell. In some aspects, methods of treating a subject in need of treatment for a tumor, the method comprising inhibiting the GCS in the tumor. In some embodiments, the methods comprise contacting a tumor cell or tumor with a GCS inhibitor. In some embodiments, the tumor cell or tumor has elevated expression of serine hydroxymethyltransferase 2 (SH1VIT2). In some aspects, methods of identifying a tumor cell or tumor that is sensitive to inhibiting the GCS are provided, the methods comprising determining whether the tumor cell or tumor overexpresses SHMT2. In some aspects, methods of identifying a candidate anti-cancer agent are provided, the methods comprising identifying or modifying a GCS inhibitor.Type: GrantFiled: February 11, 2013Date of Patent: November 15, 2016Assignee: Whitehead Institute for Biomedical ResearchInventors: Dohoon Kim, David M. Sabatini, Richard Possemato
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Publication number: 20160326535Abstract: Metabolic flux biosensors are provided herein, as are related compositions and methods useful for, inter alia, identifying factors which increase the production of metabolites and/or end products of metabolic pathways, and for the production of inter alia, metabolites and/or end products of metabolic pathways.Type: ApplicationFiled: January 8, 2015Publication date: November 10, 2016Applicants: Whitehead Institute for Biomedical Research, Massachusetts Institute of TechnologyInventors: Jose Luis Avalos, Gerald Fink, Gregory Stephanopoulos
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Publication number: 20160287734Abstract: 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 radiolalebed 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: ApplicationFiled: November 13, 2014Publication date: October 6, 2016Applicant: Whitehead Institute for Biomedical ResearchInventors: Mohammad Rashidian, Hidde L. Ploegh
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Patent number: 9457047Abstract: This invention is directed to ?-1-6-glucans, compositions and devices comprising the same, and methods of use thereof in modulating immune responses. The ?-1-6-glucans of certain embodiments of the invention are enriched for O-acetylated groups and/or conjugated to a solid support or linked to a targeting moiety.Type: GrantFiled: September 26, 2013Date of Patent: October 4, 2016Assignees: Whitehead Institute, Massachusetts Institute of Technology, Trustees of Boston University, The General Hospital CorporationInventors: Ifat Rubin-Bejerano, Gerald R. Fink, Claudia Abeijon, Daniel S. Kohane, Jason E Fuller, Robert S. Langer
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Patent number: 9434985Abstract: 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: September 22, 2009Date of Patent: September 6, 2016Assignees: University of Massachusetts, Massachusetts Institute Of Technology, President And Fellows Of Harvard College, Whitehead Institute For Biomedical ResearchInventors: Job Dekker, Erez Lieberman, Nynke Van Berkum, Andreas Gnirke, Eric Lander, Chad Nusbaum, Louise Williams, Alexandre Melnikov, Georgia Giannoukos
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Patent number: 9382515Abstract: 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 uses of said cells, and to methods for identifying agents useful for reprogramming somatic cells.Type: GrantFiled: April 7, 2008Date of Patent: July 5, 2016Assignee: Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, Yaqub Hanna, Marius Wernig, Christopher J. Lengner, Alexander Meissner, Oliver Tobias Brambrink, G. Grant Welstead, Ruth Foreman
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Patent number: 9308238Abstract: The invention provides compositions and methods useful for modulating epithelial-mesenchymal transition (EMT). Certain of the compositions and methods are useful for inducing epithelial cells to undergo an EMT. The invention further provides cells generated using the inventive methods and methods of use thereof. Certain of the compositions and methods are useful for inhibiting epithelial cells from undergoing an EMT. Certain of the compositions and methods are useful for inhibiting EMT in a subject in need thereof.Type: GrantFiled: August 30, 2011Date of Patent: April 12, 2016Assignee: Whitehead Institute for Biomedical ResearchInventors: Christina Scheel, Robert A. Weinberg
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Publication number: 20160097773Abstract: An sortase-mediated intercellular labeling method allowing for tracking ligand-receptor interaction both in vitro and in vivo; and uses thereof for tracking molecule interactions both in vitro and in vivo, identifying modulators of ligand-receptor interaction, identifying potential binding partners of a protein of interest, identifying B cells expressing high affinity B cell receptors to antigens, and identifying the antigen to which a T cell of interest binds.Type: ApplicationFiled: October 5, 2015Publication date: April 7, 2016Applicant: Whitehead Institute for Biomedical ResearchInventors: Giulia Pasqual, Gabriel Victora
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Publication number: 20160082046Abstract: 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: ApplicationFiled: May 9, 2014Publication date: March 24, 2016Applicant: Whitehead Institute for Biomedical ResearchInventors: Harvey Lodish, Hidde L. Ploegh, Hsiang-Ying Lee, Jiahai Shi, Lenka Kundrat, Novalia Pishesha
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Patent number: 9267123Abstract: Disclosed herein are methods and compositions for correction and/or mutation of genes associated with Parkinson's Disease as well as clones and animals derived therefrom.Type: GrantFiled: December 15, 2011Date of Patent: February 23, 2016Assignees: Sangamo BioSciences, Inc., Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, Josee Laganiere, Frank Soldner, Lei Zhang
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Publication number: 20160031824Abstract: The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and pharmaceutical compositions thereof. The present invention also provides methods and kits using the inventive compounds and pharmaceutical compositions for treating and/or preventing diseases associated with protein aggregation, such as amyloidoses (e.g., Parkinson's disease and Alzheimer's disease), treating and/or preventing neurodegenerative diseases, treating and/or preventing diseases associated with Tar DNA binding protein 43 kDa, reducing or preventing protein aggregation, and/or modulating E3 ubiquitin ligase in a subject in need thereof.Type: ApplicationFiled: March 17, 2014Publication date: February 4, 2016Applicants: Whitehead Institute for Biomedical Research, Massachusetts Institute of TechnologyInventors: Susan L. Lindquist, Stephen L. Buchwald, Daniel Tardiff, Nathan Jui
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Patent number: 9249444Abstract: Disclosed are genes that, when overexpressed in cells expressing alpha-synuclein, either suppress or enhance alpha-synuclein mediated cellular toxicity. Compounds that modulate expression of these genes or activity of the encoded proteins can be used to inhibit alpha-synuclein mediated toxicity and used to treat or prevent synucleinopathies such as Parkinson's disease. Also disclosed are methods of identifying inhibitors of alpha-synuclein mediated toxicity.Type: GrantFiled: June 28, 2013Date of Patent: February 2, 2016Assignee: Whitehead Institute for Biomedical ResearchInventors: Susan L. Lindquist, Aaron D. Gitler
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Publication number: 20160017292Abstract: Aspects of the invention relate to methods and related compositions for preferentially targeting cancer stem cells. In some embodiments, the methods utilize PKC-?/FRA1 pathway inhibitors to target carcinoma cells. Also provided are methods for identifying a candidate compound for selectively inhibiting growth of cancer stem cell, and methods for obtaining cells that have undergone an epithelial to mesenchymal transition.Type: ApplicationFiled: November 8, 2013Publication date: January 21, 2016Applicant: Whitehead Institute for Biomedical ResearchInventors: Wai Leong TAM, Robert A. WEINBERG
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Patent number: 9234885Abstract: Methods and assays for treating a subject with a filovirus infection using an agent that inhibits Niemann-Pick CI (NPCI), VPSII, VPSI6, VPSI8, VPS33A, VPS39, VPS41, BLOCISI, BLOCIS2, GNPTAB, PIKFYVE, ARHGAP23 or FIG4. Methods for screening for an agent that treats and/or prevents infection of a subject with a filovirus, where the methods comprise determining whether the agent inhibits one or more of Niemann-Pick CI (NPCI), VPSII, VPSI6, VPSI8, VPS33A, VPS39, VPS41. BLOCISI, BLOCIS2, GNPTAB, PIKFYVE, ARHGAP23 or FIG4, wherein an agent that inhibits one or more of NPCI, VPSII, VPSI6, VPSI8, VPS33A, VPS39, VPS41, BLOCISI, BLOCIS2, GNPTAB, PIKFYVE, ARHGAP23 or FIG4 is a candidate for treating and/or preventing an infection with a filovirus and wherein an agent that does not inhibit NPCI, VPSII, VPSI6, VPSI8, VPS33A. VPS39, VPS41, BLOCISI, BLOCIS2, GNPTAB, PIKFYVE, ARHGAP23 or FIG4 is not a candidate for treating and/or preventing an infection with a filovirus.Type: GrantFiled: January 24, 2012Date of Patent: January 12, 2016Assignees: Albert Einstein College of Medicine, Inc., President and Fellows of Harvard College, Whitehead Institute For Biomedical ResearchInventors: Kartik Chandran, Sean Whelan, Thijn Brummelkamp, Jan Carette, Matthijs Raaben
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Patent number: 9193753Abstract: The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response.Type: GrantFiled: March 14, 2013Date of Patent: November 24, 2015Assignees: University of Massachusetts, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften E.V.Inventors: Thomas Tuschl, Phillip D. Zamore, Phillip A. Sharp, David P. Bartel
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Patent number: 9181580Abstract: The present invention relates in some aspects to super-enhancers and related compositions, methods, and agents that are useful for modulating expression of cell type-specific genes that are required for maintenance of cell identity (e.g., embryonic stem cell identity) or maintenance of a disease state (e.g., cancer).Type: GrantFiled: October 24, 2014Date of Patent: November 10, 2015Assignee: Whitehead Institute for Biomedical ResearchInventors: Richard A. Young, Warren Whyte, Denes Hnisz, Jakob Loven, Heather Hoke, David Orlando, Charles Y. Lin, Tony Lee
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Patent number: 9169490Abstract: 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 5, 2012Date of Patent: October 27, 2015Assignee: Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, Konrad Hochedlinger