Patents Assigned to Whitehead Institute Biomedical Research
-
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
-
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
-
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
-
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
-
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
-
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
-
Patent number: 11739354Abstract: 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: August 29, 2023Assignee: Whitehead Institute for Biomedical ResearchInventors: Tomás Pluskal, Jing-Ke Weng
-
Patent number: 11667928Abstract: The invention provides compositions and methods for performing mammalian cell genetics, e.g., genetic screens, using near-haploid cells. The invention further provides genes and gene products isolated using the inventive methods and methods of use thereof.Type: GrantFiled: December 7, 2018Date of Patent: June 6, 2023Assignee: Whitehead Institute for Biomedical ResearchInventors: Thijn R. Brummelkamp, Jan E. Carette
-
Patent number: 11655459Abstract: 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: August 29, 2022Date of Patent: May 23, 2023Assignee: Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, Konrad Hochedlinger
-
Patent number: 11617802Abstract: Modified tRNAs can be used to express in a mammalian cell a functional gene product encoded by a gene containing a premature stop codon and/or to treat a disease mediated by a premature stop codon.Type: GrantFiled: January 16, 2021Date of Patent: April 4, 2023Assignees: CASE WESTERN RESERVE UNIVERSITY, WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCHInventors: Jeffery M. Coller, Thomas Sweet, Harvey Lodish
-
Publication number: 20230085214Abstract: Disclosed herein are compositions and methods for labeling cells using click chemistry reagents. The compositions and methods disclosed herein provide a specific and efficient means of localizing desired agents to a variety of cell types in vivo and in vitro. The compositions and methods disclosed herein can be used to deliver a variety of desired agents to a cell or population of cells to direct cell fate and/or cell differentiation.Type: ApplicationFiled: July 20, 2022Publication date: March 16, 2023Applicants: President and Fellows of Harvard College, Whitehead Institute for Biomedical ResearchInventors: Hua Wang, Andrew Salim Khalil, David J. Mooney, Rudolf Jaenisch
-
Patent number: 11597769Abstract: 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: GrantFiled: January 25, 2019Date of Patent: March 7, 2023Assignees: Massachusetts Institute of Technology, Children's Medical Center Corporation, Whitehead Institute for Biomedical ResearchInventors: Richard O. Hynes, Noor Jailkhani, Hidde L. Ploegh, Yushu Joy Xie
-
Patent number: 11571441Abstract: In some aspects, the disclosure provides methods for modulating mitochondrial transport of serine in a cell, the methods comprising modulating expression or activity of one or more sideroflexins. In some aspects, methods of identifying agents that modulate sideroflexin expression or activity are provided. In some aspects, methods of treating cancer are provided.Type: GrantFiled: March 26, 2019Date of Patent: February 7, 2023Assignee: Whitehead Institute for Biomedical ResearchInventors: David M. Sabatini, Nora Kory
-
Patent number: 11530385Abstract: The invention provides tissue culture system for primary cells (e.g. normal mammalian primary epithelial progenitors). This system includes: a) a serum-free, chemically defined cell culture media; and, b) methods for isolation and in vitro long-term propagation of primary cells (e.g. primary epithelial cells). Primary cells so isolated and cultured can be kept undifferentiated and proliferate for many weeks (>15 weeks) or population doubling (>35 PD) without senescence, or any detectable genetic alterations. Upon changing media/culture conditions, these cells can be induced to differentiate. The invention also provides methods to transform normal primary cells so cultured into “cancer stem cells.” The genetically defined cancer stem cell tumor model mimics the behavior of the disease closely, e.g., the cells are invasive, hormone responsive and metastatic when injected into mice. The tumor cells express genes that are specific to cancer stem cells identified in patient samples.Type: GrantFiled: August 1, 2017Date of Patent: December 20, 2022Assignees: Whitehead Institute for Biomedical Research, The Brigham and Women's Hospital, Inc.Inventors: Tan A. Ince, Robert A. Weinberg
-
Publication number: 20220378782Abstract: 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: ApplicationFiled: April 5, 2022Publication date: December 1, 2022Applicant: Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, Xin Tang
-
Patent number: 11499981Abstract: The invention relates to methods of identifying compounds that modulate mTORC1 activity in a cell by modulating the activity of SAMTOR, 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: GrantFiled: October 18, 2018Date of Patent: November 15, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: David M. Sabatini, Xin Gu, Jose M. Orozco
-
Patent number: 11492590Abstract: 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: GrantFiled: April 11, 2019Date of Patent: November 8, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Lee Kim Swee, Hidde L. Ploegh
-
Patent number: 11492636Abstract: Provided herein are engineered bialaphos resistance acetyltransferase variants having a modified acetyltransferase activity against tryptophan or aminoadipate, or both, as compared to a wildtype bialaphos resistance acetyltransferase (e.g., BAR or PAT). Also provided are transgenic plants comprising a bialaphos resistance acetyltransferase variant as well as methods of making such transgenic plants.Type: GrantFiled: October 17, 2017Date of Patent: November 8, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Bastien Christ, Jing-Ke Weng
-
Publication number: 20220348966Abstract: A method for producing metabolites that are heavy alcohols, and particularly branched-chain alcohols is provided, involving contacting a suitable substrate with recombinant microorganisms. The microorganisms contain at least one deletion, disruptions, or mutations from the GLN gene family, VPS gene family, GNP gene family, AVT gene family, GCN gene family, or YDR391C, and combinations thereof, and overproduce the heavy alcohol as compared to a wild-type yeast strain.Type: ApplicationFiled: September 25, 2020Publication date: November 3, 2022Applicants: The Trustees of Princeton University, Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, Kyoto UniversityInventors: José L. AVALOS, Sarah K. HAMMER, Kouichi KURODA, Gerald R. FINK, Gregory STEPHANOPOULOS
-
Patent number: RE49281Abstract: The invention provides compositions and methods of use in reprogramming somatic cells. Compositions and methods of the invention are of use, e.g., for generating or modulating (e.g., enhancing) generation of induced pluripotent stem cells by reprogramming somatic cells. The reprogrammed somatic cells are useful for a number 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 pluripotent state and/or enhances the speed and/or efficiency of reprogramming. Certain of the compositions and methods relate to modulating the Wnt pathway.Type: GrantFiled: December 13, 2019Date of Patent: November 8, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Brett Chevalier, Alexander Marson, Richard A. Young, Ruth Foreman, Rudolf Jaenisch