Patents Assigned to THE BROAD INSTITUTE, INC.
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Publication number: 20230159913Abstract: The disclosure provides methods of deaminating adenosine and cytosine bases in a target nucleic acid sequence in an USH2A gene comprising contacting the USH2A gene with a base editor in association with a guide RNA (gRNA). In some aspects, base editing is used to restore US2HA function by disrupting a splice site in the USH2A gene sequence to induce skipping of an exon containing a mutation, while in other embodiments, base editing is used to restore US2HA function by correcting a point mutation e.g., in an exon) so as to correct mutations. The disclosure also provides complexes of adenosine base editors and guide RNAs, and complexes of cytidine base editors and guide RNAs. The disclosure further provides pharmaceutical compositions and cells comprising these complexes. The disclosure also provides vectors encoding these complexes, base editors, and gRNAs. In some embodiments, the methods and compositions provided herein are used to treat Usher syndrome and autosomal recessive retinitis pigmentosa (arRP).Type: ApplicationFiled: April 27, 2021Publication date: May 25, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, Massachusetts Eye and Ear InfirmaryInventors: David R. Liu, Jonathan Ma Levy, Wei Hsi Yeh, Jason Comander, Yuki Tachida, Eric A. Pierce, Qin Liu, Nachiket Pendse
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Publication number: 20230151431Abstract: The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers that exhibit elevated expression of the glutamate/cysteine transporter SLC7A11, reduced expression of the fatty acid transporter SLC25A45 and/or reduced expression of FAM3 metabolism regulating signaling molecule B (FAM3B). In particular, the instant disclosure provides for identification of a cancer as possessing elevated SLC7A11 expression, reduced expression of SLC25A45 and/or reduced expression of FAM3B, and selecting and/or administering a glutaminase inhibitor as a therapeutic agent for such a cancer and/or subject having or at risk of developing such a cancer. Methods and compositions for therapies that combine such selection of cancers/subjects for glutaminase inhibitor therapy with other cancer therapies and/or chemotherapeutic agents are also provided.Type: ApplicationFiled: March 12, 2021Publication date: May 18, 2023Applicants: DANA-FARBER CANCER INSTITUTE, INC., THE BROAD INSTITUTE, INC.Inventors: Steven Corsello, Caitlin Harrington, Todd R. Golub
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Publication number: 20230142508Abstract: Disclosed herein are methods for inducing insulin secretion in a glucose-dependent manner and compounds for use in these methods.Type: ApplicationFiled: November 21, 2022Publication date: May 11, 2023Applicants: The Broad Institute, Inc., The General Hospital Corporation, Instituto Carlos Slim de la Salud, A.C.Inventors: Sean M. Burns, Bridget K. Wagner, Amedeo Vetere
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Publication number: 20230143552Abstract: The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity.Type: ApplicationFiled: October 7, 2022Publication date: May 11, 2023Applicants: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Edward Holson, Florence Fevrier Wagner, Michel Weiwer, Edward Scolnick, Michelle Palmer, Luka Dordevic, Michael C. Lewis, Jennifer Q. Pan, Yan-Ling Zhang, Qihong Xu
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Patent number: 11643652Abstract: Compositions and methods are provided herein for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The compositions include fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap which is synthesized by the polymerase of the fusion protein and which becomes incorporated into the target DNA molecule.Type: GrantFiled: March 31, 2021Date of Patent: May 9, 2023Assignees: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone, James William Nelson
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Patent number: 11643650Abstract: The invention provides, inter alia, methods for uniquely labeling populations of agents of interest using random combinations of oligonucleotides. The oligonucleotides may comprise a unique nucleotide sequence and/or one or more non-nucleic acid detectable moieties.Type: GrantFiled: February 18, 2020Date of Patent: May 9, 2023Assignee: The Broad Institute, Inc.Inventors: Scott Steelman, Robert Nicol, Robert E. Lintner
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Patent number: 11639523Abstract: Engineered or non-naturally occurring systems and compositions comprising a novel Cas12b and a guide molecule. Also provided include methods of use the systems and compositions, including in treating and diagnosing diseases.Type: GrantFiled: June 5, 2020Date of Patent: May 2, 2023Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGYInventors: Feng Zhang, Jonathan Gootenberg, Omar Abudayyeh, Julia Joung, Alim Ladha, Han Altae-Tran, Guilhem Faure
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Publication number: 20230127008Abstract: The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA to treat cancers, such as melanoma and glioblastoma. The disclosure also provides fusion proteins, guide RNAs and compositions comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA, for example in a STAT3 gene. In some embodiments, adenosine deaminases provided herein are used to modify the STAT3 gene so that its protein product, STAT3, is unable to be activated. In some embodiments, the methods and compositions provided herein are used to treat melanoma or glioblastoma.Type: ApplicationFiled: March 10, 2021Publication date: April 27, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Wei Hsi Yeh
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Patent number: 11633436Abstract: Microbes expressing cholesterol oxidoreductase (COR) proteins, methods of engineering the microbes expressing COR proteins, compositions and methods of using the microbes are provided.Type: GrantFiled: September 18, 2020Date of Patent: April 25, 2023Assignees: The Broad Institute, Inc., The General Hospital Corporation, President and Fellows of Harvard CollegeInventors: Douglas Kenny, Hera Vlamakis, Ramnik Xavier, Emily Balskus, Damian Plichta
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Patent number: 11633732Abstract: Provided herein is a lateral flow diagnostic device and methods of using thereof. The device comprises a substrate and a first end, wherein the first end comprises a sample loading portion. The first end may further comprise a first region loaded with a detectable ligand, a CRISPR effector system, a detection construct, a first test band comprising a biotin ligand, and a second test band comprising a capture molecule for the detectable ligand. The detection construct may comprise an RNA oligonucleotide, having a first molecule such as FITC on a first end and a second molecule such as FAM on a second end. Contacting the sample loading portion with a sample causes the sample to flow from the sample loading portion of the substrate towards the first and second capture regions, thereby generating a detectable signal, which may be indicative of a disease state.Type: GrantFiled: October 4, 2018Date of Patent: April 25, 2023Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Feng Zhang, Jonathan Gootenberg, Omar Abudayyeh
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Patent number: 11634766Abstract: Provided herein include methods and compositions for analyzing nucleic acid in individual cells. In some embodiments, the methods herein include generating, within individual cells, fragmented cellular genomic DNA and cDNA copies of cellular RNA molecules, barcoding the fragmented genomic DNA and the cDNA within each cell such that the genomic DNA and the cDNA from the same cell receive the same unique barcode sequence, isolating the barcoded genomic DNA and cDNA, and characterizing one or more features of the individual cells based, at least in part, on sequencing of the isolated barcoded genomic DNA and the cDNA.Type: GrantFiled: February 4, 2020Date of Patent: April 25, 2023Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Jason Daniel Buenrostro, Sai Ma, Aviv Regev
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Patent number: 11634755Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.Type: GrantFiled: December 17, 2021Date of Patent: April 25, 2023Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TEOHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Feng Zhang, Bernd Zetsche, Johnathan S. Gootenberg, Omar O. Abudayyeh, Ian Slaymaker
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Patent number: 11633415Abstract: The present invention includes CSNK1A1 inhibitors that are useful in treating or preventing a cancer in a subject. In certain embodiments, the cancer comprises a hematological cancer, such as but not limited to acute myeloid leukemia (AML) and/or MDS (myelodysplastic syndrome, including 5q-MDS). In other embodiments, the cancer comprises colon cancer.Type: GrantFiled: March 30, 2018Date of Patent: April 25, 2023Assignees: THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC.Inventors: Steven M. Corsello, Todd R. Golub, Eric Stefan, Robert Hilgraf
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Publication number: 20230117680Abstract: Provided herein are compounds of Formula (I?) or (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing diseases and/or conditions (e.g., neurological (e.g., neurodegenerative) disease (e.g., Alzheimer's disease, multiple sclerosis, Parkinson's disease, Huntington's disease), metabolic disorder (e.g., obesity, diabetes), proliferative disease (e.g., cancers), condition associated with autophagy (e.g., neurodegenerative disease, infection, cancer, condition associated with aging, heart disease), condition associated with aging, condition associated with modulating (e.g., regulating) the mPTP, cardiovascular condition (e.g.Type: ApplicationFiled: December 10, 2020Publication date: April 20, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Alexander A. Peterson, Alvin Hsu
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Publication number: 20230123669Abstract: The present disclosure provides a novel machine learning model capable of assisting those of ordinary skill in the art to conduct base editing by, inter alia, facilitating the selection of an appropriate guide RNA and base editor combination which are capable of conducting base editing at a certain level of efficiency and specificity on a given input target DNA sequence desired to be edited to produce an outcome genotype of interest. The disclosure also provides base editors (e.g., ABEs and CBEs), napDNAbps, cytidine deaminases, adenosine deaminases, nucleic acid sequences encoding base editors and components thereof, vectors, and cells. In addition, the disclosure provides methods of making biological or experimental training and/or validation data for training and/or validating the machine learning computational models, as well as, vectors, libraries, and nucleic acid sequences for use in obtaining said experimental training and/or validation data.Type: ApplicationFiled: February 5, 2021Publication date: April 20, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, Massachusetts Institute of Technology, The Brigham and Woman's Hospital, Inc.Inventors: David R. Liu, Mandana Arbab, Max Walt Shen, Christopher Cassa
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Patent number: 11629132Abstract: The present invention provides methods of inducing proliferation of and/or differentiating cells comprising contacting cells with compounds within the methods of the invention. The present invention further provides cells obtainable by the methods of the invention.Type: GrantFiled: September 19, 2018Date of Patent: April 18, 2023Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGYInventors: Sangeeta Bhatia, Jing Shan, Michelle Palmer, Nathan Ross
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Patent number: 11630103Abstract: The present invention provides isolated immune cells, immune cell populations and compositions, as well as markers, marker signatures and molecular targets characterising the immune cells. The cell products, substances, compositions, markers, marker signatures, molecular targets, kits of parts and methods of the present invention provide for new ways to characterise, evaluate and modulate the immune system and immune responses.Type: GrantFiled: August 17, 2017Date of Patent: April 18, 2023Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, The General Hospital CorporationInventors: Alexandra-ChloƩ Villani, Rahul Satija, Aviv Regev, Nir Hacohen
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Patent number: 11624078Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems, wherein the guide sequence is modified by secondary structure to increase the specificity of the CRISPR-Cas system and whereby the secondary structure can protect against exonuclease activity and allow for 5? additions to the guide sequence.Type: GrantFiled: April 9, 2020Date of Patent: April 11, 2023Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Feng Zhang, Omar O. Abudayyeh, James E. Dahlman, Patrick Hsu, David A. Scott
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Publication number: 20230108784Abstract: Embodiments disclosed herein are directed to engineered CRISPR-Cas effector proteins that comprise at least one modification compared to an unmodified CRISPR-Cas effector protein that enhances binding of the of the CRISPR complex to the binding site and/or alters editing preference as compared to wild type. In certain example embodiments, the CRISPR-Cas effector protein is a Type V effector protein. In certain other example embodiments, the Type V effector protein is Cpf1. Embodiments disclosed herein are directed to viral vectors for delivery of CRISPR-Cas effector proteins, including Cpf1. In certain example embodiments, the vectors are designed so as to allow packaging of the CRISPR-Cas effector protein within a single vector. There is also an increased interest in the design of compact promoters for packing and thus expressing larger transgenes for targeted delivery and tissue-specificity.Type: ApplicationFiled: May 11, 2022Publication date: April 6, 2023Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGYInventors: Feng Zhang, David Arthur Scott, Winston Xia Yan, Sourav Choudhury, Matthias Heidenreich
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Publication number: 20230108123Abstract: Described and featured are compositions and methods for treating developmental, neurodevelopmental (e.g., Fragile X syndrome (FXS) or Down syndrome (DS)), or neurodegenerative diseases or disorders (e.g., Alzheimer's disease (AD)) by increasing expression of Fragile X Mental Retardation Protein (FMRP) in patients having or having a propensity to develop such diseases or disorders.Type: ApplicationFiled: March 25, 2021Publication date: April 6, 2023Applicants: The Broad Institute, Inc., The Regents of the University of CaliforniaInventors: Lindy BARRETT, Sara G. SUSCO, Eugene YEO, Stefan AIGNER, En-Ching LUO