Patents Assigned to The Whitehead Institute for Biomedical Research
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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
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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
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Patent number: 11453858Abstract: In some aspects, described herein are cell culture media that are useful for in vitro culture of mammalian cells. The culture media contain a variety of small organic compounds that are found in normal adult human blood. Also described are methods of using the culture media for a variety of purposes. Also described are methods of treating cancer.Type: GrantFiled: November 13, 2017Date of Patent: September 27, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: David M. Sabatini, Jason Cantor
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Patent number: 11434476Abstract: The invention relates to methods of modifying DNA methylation by contacting a catalytically inactive site specific nuclease fused to an effector domain having methylation or demethylation activity and one or more guide sequences.Type: GrantFiled: August 18, 2017Date of Patent: September 6, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, X Shawn Liu, Hao Wu
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Patent number: 11408009Abstract: Transgenic host cells, vectors useful for making transgenic host cells, and kits useful for making transgenic host cells are described. Also described are transgenic plants. In some embodiments, transgenic host cells express a 4-hydroxyphenylacetaldehyde synthase (4HPAAS). In some embodiments, transgenic host cells express a tyrosol:UDP-glucose 8-O-glucosyltransferase (T8GT). The transgenic host cells are useful for biosynthesis of one or more of salidroside, icariside D2, tyrosol, and 4-hydroxypenylacetaldehyde.Type: GrantFiled: December 18, 2018Date of Patent: August 9, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Michael Torrens-Spence, Jing-Ke Weng
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Patent number: 11377466Abstract: Provided herein are analogs of the natural product icariin represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. The analogs can be used to modulate (e.g., inhibit, such as by competitive inhibition) PDE5 and thereby treat a wide range of PDE5-mediated diseases, including cardiovascular, gastrointestinal, pulmonary, musculoskeletal, neurological and reproductive diseases. Also provided herein are compositions and methods including compounds of Structural Formula (I).Type: GrantFiled: August 7, 2019Date of Patent: July 5, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Yasmin Chau, Fu-Shuang Li, Jing-Ke Weng
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Patent number: 11371019Abstract: A population of early-stage burst-forming unit-eryhtoid (BFU-E) cells characterized by low expression of the Type III Transforming Growth Factor ? Receptor (TGFRPIII) and uses thereof for producing red blood cells in vitro, genotoxicity analysis of chemicals, drug sensitivity assessment, and drug development. Also described herein are methods for producing the population of early-stage BFU-E cells and methods for producing red blood cells.Type: GrantFiled: March 3, 2017Date of Patent: June 28, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Harvey Lodish, Xiaofei Gao, Hsiang-Ying Lee
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Patent number: 11331313Abstract: 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: May 22, 2018Date of Patent: May 17, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Rudolf Jaenisch, Xin Tang
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Patent number: 11326209Abstract: The present invention relates to a cell based genomic Recorded Accumulative Memory (geRAM) system (also referred to herein as Genomically Encoded Memory (GEM)) for recoding data (i.e., changes in nucleic acid sequences in cellular DNA in response to physical and/or chemical signal(s)) from the cellular environment.Type: GrantFiled: November 7, 2014Date of Patent: May 10, 2022Assignees: Massachusetts Institute of Technology, Whitehead Institute of Biomedical ResearchInventors: Joseph M. Jacobson, Noah Jakimo, Naama Kanarek, David Sabatini
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Patent number: 11319591Abstract: Disclosed are methods for identifying the core regulatory circuitry or cell identity program of a cell or tissue, and related methods of diagnoses, screening, and treatment involving the core regulatory circuitry and/or cell identity programs identified using the methods.Type: GrantFiled: December 23, 2016Date of Patent: May 3, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Violaine Saint-Andre, Brian J. Abraham, Zi Peng Fan, Tong Ihn Lee, Richard A. Young
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Patent number: 11266695Abstract: 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: March 23, 2018Date of Patent: March 8, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Harvey Lodish, Hidde L. Ploegh, Hsiang-Ying Sherry Lee, Jiahai Shi, Lenka Hoffman, Novalia Pishesha
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Patent number: 11261453Abstract: Disclosed are yeast cells expressing a polypeptide comprising a signal sequence and a human ApoE protein. In some embodiments the polypeptide comprises ApoE2. In some embodiments the polypeptide comprises ApoE3. In some embodiments the polypeptide comprises ApoE4. Also disclosed are methods of screening yeast cells to identify compounds that prevent or suppress Apo-induced toxicity. Compounds identified by such screens can be used to treat or prevent neurodegenerative disorders such as Alzheimer's disease. Also disclosed are methods of screening yeast cells to identify genetic suppressors or enhancers of ApoE-induced toxicity. Also disclosed are genetic suppressors or enhancers of ApoE-induced toxicity identified using the methods, and human homologs thereof. Also disclosed are methods of identifying compounds that modulate expression or activity of genetic modifiers of ApoE-induced toxicity.Type: GrantFiled: September 11, 2015Date of Patent: March 1, 2022Assignee: Whitehead Institute for Biomedical ResearchInventors: Susan L. Lindquist, Priyanka Narayan
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Patent number: 11225469Abstract: The present invention provides compounds of Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, pro-drugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I), (II) or (III) for treating diseases associated with the over-expression of phosphoglycerate dehydrogenase (PHGDH) in a subject, such as proliferative diseases (e.g., cancers (e.g., breast cancer, ER negative breast cancer, melanoma, cervical cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the activity of PHGDH or inhibit the serine biosynthetic pathway, or both.Type: GrantFiled: January 15, 2016Date of Patent: January 18, 2022Assignees: Whitehead Institute for Biomedical Research, Dana-Farber Cancer Institute, Inc., The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: David M. Sabatini, Michael Pacold, Matthew B. Boxer, Jason M. Rohde, Kyle R. Brimacombe, Min Shen, Ganesha Bantukallu, Li Liu
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Publication number: 20220002769Abstract: 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: March 3, 2021Publication date: January 6, 2022Applicant: Whitehead Institute for Biomedical ResearchInventors: Tomás Pluskal, Jing-Ke Weng
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Publication number: 20220002768Abstract: 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: March 3, 2021Publication date: January 6, 2022Applicant: Whitehead Institute for Biomedical ResearchInventors: Tomás Pluskal, Jing-Ke Weng
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Patent number: 11208653Abstract: Methods and compositions for increasing RNAi efficiency through single nucleotide mismatches.Type: GrantFiled: April 27, 2017Date of Patent: December 28, 2021Assignee: Whitehead Institute for Biomedical ResearchInventors: Grace Chen, David Bartel, Hazel Sive
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Publication number: 20210353566Abstract: The invention relates to methods of using choline supplementation for treating APOE4-related disorders. In particular the methods are accomplished by administering choline treatment paradigms to re-establish lipid homeostasis in APOE4 carriers.Type: ApplicationFiled: May 12, 2021Publication date: November 18, 2021Applicants: Massachusetts Institute of Technology, Whitehead Institute for Biomedical ResearchInventors: Li-Huei Tsai, Yuan-Ta Lin, Julia Bonner, Priyanka Narayan, Grzegorz Sienski
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Patent number: 11149267Abstract: The present invention generally relates to libraries, kits, methods, applications and screens used in functional genomics that focus on gene function in a cell and that may use vector systems and other aspects related to Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas systems and components thereof. The present invention also relates to rules for making potent single guide RNAs (sgRNAs) for use in CRISPR-Cas systems. Provided are genomic libraries and genome wide libraries, kits, methods of knocking out in parallel every gene in the genome, methods of selecting individual cell knock outs that survive under a selective pressure, methods of identifying the genetic basis of one or more medical symptoms exhibited by a patient, and methods for designing a genome-scale sgRNA library.Type: GrantFiled: April 28, 2016Date of Patent: October 19, 2021Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, Whitehead Institute for Biomedical ResearchInventors: Tim Wang, David Sabatini, Eric Lander
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Patent number: 11136548Abstract: Described herein are cell culture media useful for the differentiation of human pluripotent stem cells into microglia. The methods described herein relate to in vitro generation of expandable, bankable, microglial cells by directed differentiation from human pluripotent stem cells (induced or embryonic). Using only defined cell culture media, differentiation of pluripotent stem cells is directed down a mesodermal path, in a rapid and scalable fashion, to generate cells adopting signatures of their in vivo counterparts, including gene expression, protein marker expression and functionality.Type: GrantFiled: June 24, 2016Date of Patent: October 5, 2021Assignee: Whitehead Institute for Biomedical ResearchInventors: Julien Muffat, Yun Li, Rudolf Jaenisch
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Patent number: 11092608Abstract: The invention relates to methods of identifying compounds that modulate mTORC1 activity in a cell by modulating the activity of CASTOR1, 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: December 28, 2016Date of Patent: August 17, 2021Assignee: Whitehead Institute for Biomedical ResearchInventors: David M. Sabatini, Lynne Chantranupong, Robert A. Saxton, Steven P. Gygi, Melanie P. Gygi