Patents Assigned to The Broad Institute
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Patent number: 12188925Abstract: A system and method for isolating target substrates includes a microfluidic chip, comprising a plurality of processing units, each processing unit comprising: an inlet port, a plurality of first chambers connected to the inlet port by a fluid channel, the fluid channel comprising a plurality of valves, a plurality of second chambers, each of the second chambers connected to a respective first chamber by a fluid channel, each fluid channel including a controllable blocking valve, and a plurality of respective outlet ports, each outlet port in fluid communication with a respective one of said second chambers and each outlet port including a blocking valve. A magnet is adjacent the microfluidic chip and is movable relative to the microfluidic chip. A valve control is capable of actuating certain ones of the controllable blocking valves in response to a control signal.Type: GrantFiled: January 29, 2021Date of Patent: January 7, 2025Assignees: The Broad Institute, Inc., The General Hospital Corporation, Massachusetts Institute of TechnologyInventors: Paul Blainey, Dwayne Vickers, Nir Hacohen
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Publication number: 20240425938Abstract: This disclosure relates to methods and compositions useful for detecting and monitoring low-frequency mutations. Methods and compositions described herein can be used to guide clinical decisions, for example, by informing on which antibiotics should be avoided, or conversely, which antibiotics should be actively used in the case of compounds that select against a specific type of resistance.Type: ApplicationFiled: August 9, 2024Publication date: December 26, 2024Applicants: The Broad Institute, Inc., The Children's Medical Center Corporation, Technion Research & Development Foundation LimitedInventors: Gregory P. PRIEBE, Roy KISHONY, Hattie CHUNG, Matthew M. SCHAEFERS
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Patent number: 12171783Abstract: The subject matter disclosed herein is generally directed to compositions and methods for treating diffuse gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-gliomas). Disclosed herein are gene signatures specific for tumor cell types and compositions for treatment of H3K27M gliomas. In one embodiment, PRC1 is targeted in a treatment regimen for H3K27M-gliomas.Type: GrantFiled: November 13, 2018Date of Patent: December 24, 2024Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, The General Hospital Corporation, Dana-Farber Cancer Institute, Inc.Inventors: Mario Suva, Bradley Bernstein, Aviv Regev, Mariella Filbin, Itay Tirosh, Volker Hovestadt
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Publication number: 20240417753Abstract: The present disclosure provides new prime editor guide RNAs for prime editing, constructs for prime editing, and methods for using same. In addition, the present disclosure provides compositions and methods 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 (e.g., insertion or deletion). The nucleotide change can include a single-nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides 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 prime editor RNA (PEgRNA).Type: ApplicationFiled: March 19, 2020Publication date: December 19, 2024Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, Massachusetts Institute of TechnologyInventors: David R. Liu, Andrew Vito Anzalone, Max Walt Shen
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Publication number: 20240417715Abstract: The present disclosure provides compositions and methods for the targeted modification of RNA molecules by RNA prime editing. The compositions and methods may be conducted invitro or in vivo within cells (e.g., human cells) for the therapeutic correction of disease-causing mutations and/or installation of motifs or mutations in RNA molecules of interest as a tool for scientific research. The disclosure provides compositions and methods for conducting RNA prime editing of a target RNA molecule (e.g., an RNA transcript) that enables the incorporation of one or more nucleotide changes and/or targeted mutagenesis of a target RNA molecule. The nucleotide change can include a single-nucleotide change, an insertion of one or more nucleotides, or a deletion of one or more nucleotides.Type: ApplicationFiled: October 9, 2020Publication date: December 19, 2024Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone, James William Nelson, Peter J. Chen
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Publication number: 20240417719Abstract: Disclosed are constructs, systems, and methodologies using prime editing (PE), twin prime editing (twinPE), or multi-flap prime editing to carry out site-specific and large-scale genetic modification, such as, but not limited to, insertions, deletions, inversions, replacements, and chromosomal translocations of whole or partial genes (e.g., whole gene, gene exons and/or introns, and gene regulatory regions). In certain embodiments, the disclosure provides constructs, systems, and methods using prime editing (PE), e.g., single flap or “classical” PE or twinPE or multi-flap PE, to install one or more target sites for site specific recombination in a target genomic locus (e.g., a specific gene, exon, intron, or regulatory sequence), which may then be acted on by one or more site-specific recombinases to effectuate a large-scale genetic modification, such as an insertions, deletions, inversions, replacements, and chromosomal translocations.Type: ApplicationFiled: October 25, 2022Publication date: December 19, 2024Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Andrew Vito Anzalone, Christopher J. Podracky, Xin Gao
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Publication number: 20240412814Abstract: The disclosure features compositions and methods that are useful for determining the fraction of tumor-derived DNA (tumor fraction; TF) in cell free DNA (cfDNA). The methods involve calculating the fraction of tumor-derived DNA in the cfDNA using a combination of copy number alteration data and fragment length distribution data.Type: ApplicationFiled: August 23, 2024Publication date: December 12, 2024Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, The General Hospital CorporationInventors: Gad GETZ, Ziao LIN, Donald STEWART
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Patent number: 12165747Abstract: The present invention discloses novel methods and uses thereof for producing molecular spatial maps of metastatic breast cancer (MBC) and ductal carcinoma in situ of the breast (DCIS). A specific list of genes are identified using single-cell RNA sequencing and single-nucleus RNA sequencing and are used for RNA visualization of MBC and DCIS tissue microenvironment. Unexpected subtypes of tumor cells are revealed, and methods for identifying molecular biomarkers for MBC in the bone and breast and DCIS are disclosed. Furthermore, methods for identifying therapeutic agents and uses thereof for treating MBC and DCIS as well as compositions thereof comprising such identified therapeutic agents are provided.Type: GrantFiled: January 22, 2021Date of Patent: December 10, 2024Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, Dana-Farber Cancer Institute, Inc.Inventors: Aviv Regev, Johanna Klughammer, Daniel Abravanel
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Patent number: 12161694Abstract: Computational and functional analysis identified the neuropeptide receptor Nmur1 as selectively expressed on Type 2 innate lymphoid cells (ILC2s). While both IL-33 and IL-25 promote ILC activation in vivo, IL-33 induces robust ILC proliferation, whereas ILCs activated with IL-25 do not proliferate as robustly and up-regulate Nmur1 expression. Treatment with neuromedin U (NMU), the neuropeptide ligand of Nmur1, had little effect on its own. Co-administration of IL-25 with NMU, however, dramatically amplified allergic lung inflammation and induced the proliferation and expansion of specific ILC2 subsets, characterized by a molecular signature unique to pro-inflammatory ILC2s. The results demonstrate that Nmur1 signaling strongly modulates IL-25-mediated ILC2 responses, resulting in highly proliferative pro-inflammatory ILCs, and highlights the importance of neuro-immune crosstalk in allergic inflammatory responses at mucosal surfaces.Type: GrantFiled: March 23, 2018Date of Patent: December 10, 2024Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, The Brigham and Women's Hospital, Inc.Inventors: Antonia Wallrapp, Samantha J. Riesenfeld, Patrick R. Burkett, Monika S. Kowalczyk, Aviv Regev, Vijay K. Kuchroo
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Publication number: 20240401018Abstract: The specification provides programmable base editors that are capable of introducing a nucleotide change and/or which could alter or modify the nucleotide sequence at a target site in a double-stranded nucleotide sequence, such as, a chromosome, genome, or a mitochondrial DNA (mtDNA), with high specificity and efficiency. Moreover, the disclosure provides fusion proteins and compositions comprising a programmable DNA binding protein (e.g., a mitoTALE, a mitoZFP, or a CRISPR/Cas9) and evolved double-stranded DNA deaminase domains that is capable of being delivered to a cell nucleus and/or a mitochondria and carrying out precise installation of nucleotide changes in the target a double-stranded nucleotide sequence, such as, a chromosome, genome, or mtDNA. The fusion proteins and compositions are not limited for use with mtDNA, but may be used for base editing of any double-stranded target DNA.Type: ApplicationFiled: April 12, 2022Publication date: December 5, 2024Applicants: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Beverly Mok
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Publication number: 20240401150Abstract: Described herein are pancreatic ductal adenocarcinoma (PDAC) signatures and methods of detecting the same in a sample from a subject. Also described herein, are methods of methods of diagnosing, prognosing, and/or treating PDAC in a subject that can include detecting one or more of the PDAC signatures.Type: ApplicationFiled: August 23, 2024Publication date: December 5, 2024Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, THE GENERAL HOSPITAL CORPORATIONInventors: William HWANG, Jimmy GUO, Tyler JACKS, Aviv REGEV, Karthik JAGADEESH, Hannah HOFFMAN
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Patent number: 12157760Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. The disclosure provides fusion proteins of nucleic acid programmable DNA binding proteins (napDNAbp), e.g., Cas9 or variants thereof, and nucleic acid editing proteins such as cytidine deaminase domains (e.g., novel cytidine deaminases generated by ancestral sequence reconstruction), and adenosine deaminases that deaminate adenine in DNA. Aspects of the disclosure relate to fusion proteins (e.g., base editors) that have improved expression and/or localize efficiently to the nucleus. In some embodiments, base editors are codon optimized for expression in mammalian cells. In some embodiments, base editors include multiple nuclear localization sequences (e.g., bipartite NLSs), e.g., at least two NLSs.Type: GrantFiled: May 23, 2019Date of Patent: December 3, 2024Assignees: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: David R. Liu, Luke W. Koblan, Christopher Gerard Wilson, Jordan Leigh Doman
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Publication number: 20240392311Abstract: Disclosed herein are modified mRNAs with poly(A) tails containing one or more additional poly-A tails or 5? caps, which may be made by ligation of nucleic acids onto the 3? terminal end or 5? terminal end of an RNA, respectively. Also provided are compositions comprising one or more modified mRNAs provided herein, and methods of using said compositions for therapeutic or agricultural applications.Type: ApplicationFiled: July 17, 2024Publication date: November 28, 2024Applicants: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Xiao WANG, Hongyu CHEN, Abhishek ADITHAM, Jianting GUO
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Patent number: 12152008Abstract: Provided herein are compounds useful for the treatment of various proliferative diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compositions, and may be used in methods of treatment and/or prophylaxis of proliferative diseases, including cancer, and more specifically, pancreatic cancer.Type: GrantFiled: September 4, 2020Date of Patent: November 26, 2024Assignees: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., President and Fellows of Harvard CollegeInventors: Srivatsan Raghavan, Bruce Kuan-Yee Hua, Shubhroz Gill, Stuart Schreiber, William Hahn, Paul Clemons, Raymond Ng, Partha Nag
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Patent number: 12152041Abstract: The present invention relates to macrocyclic indole derivatives of general formula (I): in which R1, R2, R3, R4, R5, R6, A and L are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.Type: GrantFiled: March 10, 2022Date of Patent: November 26, 2024Assignees: The Broad Institute, Inc., Bayer Aktiengesellschaft, Bayer Pharma AktiengesellschaftInventors: Steven James Ferrara, Michael H. Serrano-Wu, Chris Lemke, David McKinney, Mark Fitzgerald, Christopher Nasveschuk, Kiel Lazarski, Laura Furst, Guo Wei, Patrick Ryan McCarren, Kai Thede, Anne Mengel, Clara Christ, Joachim Kuhnke, Sarah Anna Liesa Johannes, Philipp Buchgraber, Ulrich Klar, Ulrike Rauh, Stefan Kaulfuss, Amaury Ernesto Fernandez-Montalvan, Nicolas Werbeck, Ursula Mönning
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Patent number: 12146880Abstract: The present invention relates to compositions which may comprise a non-naturally occurring or engineered artificial transcription factor, wherein the transcription factor may comprise a sequence specific DNA binding domain, a sliding domain, and one or more linkers, wherein the DNA binding domain and the sliding domain are operably connected by the one or more linkers, and uses thereof. Methods involving the use of a non-naturally occurring or engineered artificial transcription factors and pharmaceutical compositions, methods for treating cancer, a degenerative disease, a genetic disease or an infectious disease as well as diagnostic methods are also contemplated by the present invention.Type: GrantFiled: October 13, 2020Date of Patent: November 19, 2024Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Paul Blainey, Anthony Kulesa, Kan Xiong
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Publication number: 20240376530Abstract: The present disclosure provides methods and systems for mapping gene and protein expression in a cell (i.e., mapping gene and protein expression within the same cell simultaneously). The present disclosure also provides methods for diagnosing a disease or disorder (e.g., a neurological disorder such as Alzheimer's disease) in a subject. Methods of screening for a candidate agent capable of modulating gene and/or protein expression are also provided by the present disclosure. The present disclosure also provides methods for treating a disease or disorder, such as Alzheimer's disease, in a subject in need thereof. A plurality of oligonucleotide probes, which may be useful for performing the methods described herein, are also described by the present disclosure, as well as kits comprising any of the oligonucleotide probes described herein.Type: ApplicationFiled: May 27, 2022Publication date: November 14, 2024Applicants: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Xiao Wang, Hu Zeng, Jingyi Ren
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Publication number: 20240371184Abstract: Computer-implemented methods, computer program products, and systems determine an omics profiles of a cell using microscopy imaging data. In one aspect, a computer-implemented method determines an omics profiles of a cell using microscopy imaging data by a) receiving microscopy imaging data of a cell or a population of cells; b) determining a targeted expression profile of a set of target genes from the microscopy imaging data using a first machine learning model, the target genes identifying a cell type or cell state of interest; and c) determining a single-cell omics profile for the population of cells using a second machine learning algorithm model. The targeted expression profile and a reference single-cell RNA-seq data set are used as inputs for the second machine learning model.Type: ApplicationFiled: May 15, 2024Publication date: November 7, 2024Applicants: The Broad Institute, Inc., The General Hospital Corporation, MASSACHUSETTS INSTITUTE OF TECHNOLOGYInventors: Charles COMITER, Jian SHU, Aviv REGEV, Koseki KOBAYASHI-KIRSCHVINK, Tommaso BIANCALANI
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Patent number: 12131803Abstract: Embodiments disclosed herein provide methods, systems, and computer program products that utilize long-range phase information to detect subtle chromosome imbalances in genotype data. Clonal expansions result from mutation followed by selective proliferation, and the embodiments disclosed herein may be used to somatic structural variant events (SVs) predictive or diagnostic of cancer and other diseases.Type: GrantFiled: October 17, 2018Date of Patent: October 29, 2024Assignees: The Broad Institute, Inc., President and Fellows of Harvard CollegeInventors: Giulio Genovese, Po-Ru Loh, Steven McCarroll
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Patent number: 12131498Abstract: A way to design a codebook for estimating the type of a molecule at a particular location in a fluorescence microscopy image makes use of one or both of (1) knowledge of the non-uniform prior distribution of molecule types (i.e., some types are known a priori to occur more frequently than others) and/or knowledge of co-occurrence of molecule types at close locations (e.g., in a same cell); and (2) knowledge of a model of the (e.g., random) process that yields the intensities that are expected at a location when a molecule with a particular subset of markers (i.e., a molecule of a type that has been assigned a codeword that defines that subset) is present at that location. The codebook design may provide experimental efficiency by reducing the number of images that need to be acquired and/or improve classification or detection accuracy by making the codewords for different molecule types more distinctive.Type: GrantFiled: April 27, 2022Date of Patent: October 29, 2024Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, Yeda Research and Development Co. LTD. of Weizmann Institute of Science, National University of Ireland MaynoothInventors: Mehrtash Babadi, Luca D'Alessio, Muriel Medard, Ken Duffy, Yonina Eldar, Litian Liu