Patents Assigned to Whitehead Institute for Biomedical Research
  • Patent number: 10526651
    Abstract: Disclosed are compositions and methods for modulating expression of genes that function at the step of ER to Golgi trafficking. 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: Grant
    Filed: January 18, 2013
    Date of Patent: January 7, 2020
    Assignees: Whitehead Institute for Biomedical Research, The Curators of the University of Missouri
    Inventors: Susan L. Lindquist, Aaron D. Gitler, Anil Cashikar, Antony A. Cooper, Cole M. Haynes
  • Publication number: 20190359933
    Abstract: Non-genetically engineered mammalian cells modified by sortase-mediated conjugation of an agent thereto are provided. Methods of conjugating agents to non-genetically engineered mammalian cells using sortase are provided. Methods of using the cells, e.g., for diagnostic and/or therapeutic purposes, are provided.
    Type: Application
    Filed: April 11, 2019
    Publication date: November 28, 2019
    Applicant: Whitehead Institute for Biomedical Research
    Inventors: Lee Kim Swee, Hidde L. Ploegh
  • Patent number: 10472625
    Abstract: 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: Grant
    Filed: October 16, 2015
    Date of Patent: November 12, 2019
    Assignees: Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften E.V., Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, University of Massachusetts
    Inventors: Thomas Tuschl, Phillip D. Zamore, Phillip A. Sharp, David P. Bartel
  • Patent number: 10471099
    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: May 9, 2014
    Date of Patent: November 12, 2019
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Harvey Lodish, Hidde L. Ploegh, Hsiang-Ying Lee, Jiahai Shi, Lenka Hoffman, Novalia Pishesha
  • Patent number: 10457917
    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: July 9, 2018
    Date of Patent: October 29, 2019
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Rudolf Jaenisch, Konrad Hochedlinger
  • Patent number: 10428335
    Abstract: Disclosed are yeast cells expressing TAR DNA-binding protein 43 (TDP-43) and methods of screening yeast cells to identify compounds that prevent or suppress TDP-43-induced toxicity, compounds that inhibit the formation or maintenance of cytoplasmic inclusions of TDP-43, genetic suppressors or enhancers of TDP-43-induced toxicity, and genetic suppressors or enhancers of the formation or maintenance of cytoplasmic inclusions of TDP-43. Compounds identified by such screens can be used to treat or prevent TDP-43 proteinopathies such as frontotemporal lobar degeneration or amyotrophic lateral sclerosis.
    Type: Grant
    Filed: September 20, 2018
    Date of Patent: October 1, 2019
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Susan L. Lindquist, Aaron D. Gitler
  • Patent number: 10426757
    Abstract: 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: Grant
    Filed: May 29, 2015
    Date of Patent: October 1, 2019
    Assignees: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
    Inventors: David M. Sabatini, Omer Yilmaz, Maria Mihaylova
  • Patent number: 10398672
    Abstract: Aspects of the disclosure relate to methods that involve activating the Protein Kinase A (PKA) pathway to induce cancer stem cells (CSCs) to undergo a mesenchymal to epithelial transition. Methods provided herein are useful, in some embodiments, because they render CSCs amenable to treatment with conventional cancer therapies. In some embodiments, methods are provided that involve assaying PKA pathway activity to identify compounds that selectively target CSCs.
    Type: Grant
    Filed: April 29, 2015
    Date of Patent: September 3, 2019
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Diwakar Pattabiraman, Brian Bierie, Wai Leong Tam, Robert A. Weinberg
  • Publication number: 20190256818
    Abstract: Non-genetically engineered mammalian cells modified by sortase-mediated conjugation of an agent thereto are provided. Methods of conjugating agents to non-genetically engineered mammalian cells using sortase are provided. Methods of using the cells, e.g., for diagnostic and/or therapeutic purposes, are provided.
    Type: Application
    Filed: February 15, 2019
    Publication date: August 22, 2019
    Applicant: Whitehead Institute for Biomedical Research
    Inventors: Lee Kim Swee, Hidde L. Ploegh
  • Publication number: 20190112394
    Abstract: Methods and reagents for the installation of click chemistry handles on target proteins are provided, as well as modified proteins comprising click chemistry handles. Further, chimeric proteins, for example, bi-specific antibodies, that comprise two proteins conjugated via click chemistry, as well as methods for their generation and use are disclosed herein.
    Type: Application
    Filed: September 24, 2018
    Publication date: April 18, 2019
    Applicant: Whitehead Institute for Biomedical Research
    Inventor: Whitehead Institute for Biomedical Research
  • Patent number: 10260038
    Abstract: Non-genetically engineered mammalian cells modified by sortase-mediated conjugation of an agent thereto are provided. Methods of conjugating agents to nongenetically engineered mammalian cells using sortase are provided. Methods of using the cells, e.g. a method of modulating an immune response of a subject to an entity of interest, a method of neutralizing a substance in the body of a subject, a method of treating a subject in need of treatment for deficiency of a protein, and a method of treating a subject in need of treatment for a disease, are provided.
    Type: Grant
    Filed: May 9, 2014
    Date of Patent: April 16, 2019
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Lee Kim Swee, Hidde L. Ploegh
  • Patent number: 10240160
    Abstract: Disclosed are yeast cells expressing a polypeptide comprising a signal sequence and a human amyloid beta protein. Also disclosed are methods of screening yeast cells to identify compounds that prevent or suppress amyloid beta-induced toxicity and genetic suppressors or enhancers of amyloid beta-induced toxicity. Compounds identified by such screens can be used to treat or prevent neurodegenerative disorders such as Alzheimer's disease.
    Type: Grant
    Filed: May 4, 2017
    Date of Patent: March 26, 2019
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Kent E. S. Matlack, Susan L. Lindquist, Sebastian Treusch
  • Publication number: 20190010507
    Abstract: Disclosed are yeast cells expressing TAR DNA-binding protein 43 (TDP-43) and methods of screening yeast cells to identify compounds that prevent or suppress TDP-43-induced toxicity, compounds that inhibit the formation or maintenance of cytoplasmic inclusions of TDP-43, genetic suppressors or enhancers of TDP-43-induced toxicity, and genetic suppressors or enhancers of the formation or maintenance of cytoplasmic inclusions of TDP-43. Compounds identified by such screens can be used to treat or prevent TDP-43 proteinopathies such as frontotemporal lobar degeneration or amyotrophic lateral sclerosis.
    Type: Application
    Filed: September 20, 2018
    Publication date: January 10, 2019
    Applicant: Whitehead Institute for Biomedical Research
    Inventors: Susan L. Lindquist, Aaron D. Gitler
  • Patent number: 10168338
    Abstract: The present invention provides methods of identifying modulators of mTORC1 based upon their effect on GATOR2-Sestrin binding or Sestrin-leucine binding; and the use of such modulators to alter mTORC1 activity in a cell and to treat disease and conditions that are effected by mTORC1 activity.
    Type: Grant
    Filed: September 11, 2015
    Date of Patent: January 1, 2019
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: David M. Sabatini, Lynne Chantranupong, Rachel L. Wolfson, Jose Orozco, Robert A. Saxton, Shomit Sengupta
  • Patent number: 10160977
    Abstract: 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: Grant
    Filed: October 2, 2015
    Date of Patent: December 25, 2018
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Denes Hnisz, Brian Abraham, Tong Ihn Lee, Richard A. Young
  • Publication number: 20180346899
    Abstract: 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: Application
    Filed: August 3, 2018
    Publication date: December 6, 2018
    Applicant: Whitehead Institute for Biomedical Research
    Inventors: Giulia Pasqual, Gabriel Victora
  • Patent number: 10126303
    Abstract: The invention relates to methods of identifying compounds that modulate mTORC1 activity in a cell by modulating the activity of SLC38A9 (NCBI Gene ID: 153129), as well as to the use of such identified compounds in the modulation of mTORC1 and the treatment of diseases and conditions characterized by aberrant mTORC1 activity.
    Type: Grant
    Filed: May 1, 2015
    Date of Patent: November 13, 2018
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: David M. Sabatini, Shuyu Wang, Zhi Tsun
  • Patent number: 10123985
    Abstract: Provided herein are methods, compositions, and systems for treating mitochondrial disorders (e.g., MERRF, MELAS, Kearns-Sayre syndrome, chronic progressive external ophthalmoplegia, diabetes mellitus and deafness, lactic acidosis, Leber's hereditary optic neuropathy, Wolff-Parkinson-White syndrome, Leigh syndrome, NARP, myoneurogenic gastrointestinal encephalopathy, mitochondrial DNA depletion syndrome) or neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease) by administering aspartate, or an analog or prodrug thereof, or an agent that increases intracellular levels of aspartate. Pharmaceutical compositions and kits for use in treating mitochondrial disorders and neurodegenerative diseases are also described herein. Also provided are methods for treating disease by modulating the redox state of a cell, and methods of treating a proliferative disease by administering a cytosolic aspartate aminotransferase (GOT1) inhibitor.
    Type: Grant
    Filed: June 8, 2016
    Date of Patent: November 13, 2018
    Assignees: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Howard Hughes Medical Institute
    Inventors: David M. Sabatini, Kivanc Birsoy, Matthew George Vander Heiden, Lucas Bryan Sullivan, Dan Yi Gui
  • Patent number: 10106778
    Abstract: 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: Grant
    Filed: November 8, 2013
    Date of Patent: October 23, 2018
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Wai Leong Tam, Robert A. Weinberg
  • Patent number: 10106803
    Abstract: Disclosed are yeast cells expressing TAR DNA-binding protein 43 (TDP-43) and methods of screening yeast cells to identify compounds that prevent or suppress TDP-43-induced toxicity, compounds that inhibit the formation or maintenance of cytoplasmic inclusions of TDP-43, genetic suppressors or enhancers of TDP-43-induced toxicity, and genetic suppressors or enhancers of the formation or maintenance of cytoplasmic inclusions of TDP-43. Compounds identified by such screens can be used to treat or prevent TDP-43 proteinopathies such as frontotemporal lobar degeneration or amyotrophic lateral sclerosis.
    Type: Grant
    Filed: July 14, 2017
    Date of Patent: October 23, 2018
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Susan L. Lindquist, Aaron D. Gitler