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71. 发明申请

WO2020243657A1 REPRODUCIBLE BRAIN ORGANOIDS AND METHODS OF MAKING 审中-公开
公开(公告)号：WO2020243657A1
公开(公告)日：2020-12-03
申请号：PCT/US2020/035439
申请日：2020-05-29
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , THE BROAD INSTITUTE, INC.
发明人： VELASCO, Silvia , ARLOTTA, Paola
IPC分类号： A01K67/027 , A61K35/12 , C12N5/071 , C12N5/0793 , C12N5/0797
摘要： The present disclosure is directed to methods of producing dorsal forebrain organoids having cores with a very low incident of apoptotic and hypoxic cells and having highly similar cell types and cell type prevalence. The present disclosure is also directed to compositions comprising such organoids and the use of such organoids for the screening of agents.

72. 发明申请

WO2020242929A1 COPOLYMERS FOR STABILIZING EMULSIONS AND/OR FORMING INTERFACIAL FILMS, AND METHODS THEREOF 审中-公开
公开(公告)号：WO2020242929A1
公开(公告)日：2020-12-03
申请号：PCT/US2020/034187
申请日：2020-05-22
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE
发明人： WEITZ, David A. , WERNER, Joerg G. , BROUCHON, Julie V. , HEYMAN, John , DEVENEY, Brendan
IPC分类号： B01F17/00 , A61K9/107 , B01F3/08 , B01J13/16 , C08F220/06 , C08F220/52
摘要： The present invention generally relates to polymers and, in particular, to copolymers for stabilizing, e.g., emulsions or droplets. In certain aspects, the copolymers may comprise a relatively hydrophobic monomer and a relatively hydrophilic monomer polymerized together (e.g., randomly) to form the copolymer. Examples of hydrophobic monomers include methacrylates and vinylphenyls; examples of hydrophilic monomers include boronic acids or acid derivatives.

73. 发明申请

WO2020237043A1 HUMAN TACTILE PREPULSE INHIBITION ASSAY 审中-公开
公开(公告)号：WO2020237043A1
公开(公告)日：2020-11-26
申请号：PCT/US2020/033984
申请日：2020-05-21
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE
发明人： GINTY, David, D. , OREFICE, Lauren, L.
IPC分类号： A61K31/445 , A61K31/451 , A61K45/00 , A61P25/18 , A61P43/00 , C07D211/22
摘要： In some aspects, the disclosure relates to a prepulse inhibition (PPI) assay comprising the steps of, administering a tactile prepulse to a human subject, administering a startle stimulus to the subject, and measuring the subject's response to the startle stimulus. In another aspect, the disclosure relates to a method for evaluating tactile hypersensitivity and/or sensorimotor impairment in a human subject, comprising, administering to the subject a PPI assay according to any one of the preceding claims, comparing the assay results to neuro-typical controls, and determining the degree of tactile hypersensitivity and/or sensorimotor impairment in the subject.

74. 发明申请

WO2020214885A1 IMAGING-BASED POOLED CRISPR SCREENING 审中-公开
公开(公告)号：WO2020214885A1
公开(公告)日：2020-10-22
申请号：PCT/US2020/028632
申请日：2020-04-17
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE
发明人： ZHUANG, Xiaowei , WANG, Chong , LU, Tian
IPC分类号： C12Q1/6832 , C12Q1/68 , C12N9/22 , C12N15/11
摘要： The present invention generally relates to imaging cells, for example, to determine phenotypes and/or genotypes in populations of cells, e.g., to build genotype-phenotype corresponse for high-throughput screening. In some cases, the cells may be manipulated, e.g., using CRISPR or other techniques. In certain embodiments, nucleic acids may be introduced to the cell, e.g., using a lentivirus. The nucleic acids may contain a guide portion comprising a DNA or RNA recognition sequence, a reporter portion, and an identification portion comprising one or more read sequences. The guide portion may be used to alter the phenotype of the cells, e.g., using a sequence, e.g., an sgRNA sequence, that can be targeted using CRISPR or other techniques, and in some cases, the phenotype of the cells may be determined using various imaging approaches. The identification portion may be determined using MERFISH or other suitable techniques. In addition, in some cases, association or colocalization between determination of the reporter and the read sequences may substantially improve decoding accuracy, e.g., due to lowered misidentification of background signals. Other aspects are generally directed to compositions or devices for use in such methods, kits for use in such methods, or the like.

75. 发明申请

WO2020198450A1 METHODS OF TREATING INFLUENZA A VIRUS INFECTIONS 审中-公开
公开(公告)号：WO2020198450A1
公开(公告)日：2020-10-01
申请号：PCT/US2020/024919
申请日：2020-03-26
申请人： THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE , THE GENERAL HOSPITAL CORPORATION
发明人： LI, Bo , HACOHEN, Nir
IPC分类号： A61K38/02 , A61K39/395 , A61P31/16
摘要： Methods of treating influenza A are provided, comprising administering to a subject at least one agent selected from a WDR7 inhibitor, a CCDC115 inhibitor, a TMEM199 inhibitor, and a CMTR1 inhibitor

76. 发明申请

WO2020191242A1 METHODS AND COMPOSITIONS FOR EDITING NUCLEOTIDE SEQUENCES 审中-公开
公开(公告)号：WO2020191242A1
公开(公告)日：2020-09-24
申请号：PCT/US2020/023724
申请日：2020-03-19
申请人： THE BROAD INSTITUTE, INC. , PRESIDENT AND FELLOWS OF HARVARD COLLEGE
发明人： LIU, David, R. , ANZALONE, Andrew, Vito , DAVIS, Jessie, Rose , LEVY, Jonathan, Ma
IPC分类号： C12N9/12 , C12N9/22 , C12N15/11 , C12N15/62 , C12N15/10
摘要： 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. 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 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 homologous to a strand of the targeted endogenous DNA sequence to be edited, but which contains the desired one or more nucleotide changes and which, following synthesis by the polymerase (e.g., reverse transcriptase), becomes incoporated into the target DNA molecule. Also disclosed herein are various methods that leverage prime editing, including treating trinucleotide repeat contraction diseases, installing targeted peptide tags, treating prion disease through the intallation of protection mutations, manipulating RNA-encoding genes for the installation of RNA tags for controlling the function and expression of RNA, using prime editing to construct sophisticated gene libraries, using prime editing to insert immunoepitopes into proteins, use of prime editing to insert inducible dimerization domains into protein targets, and delivery methods, among others.

77. 发明申请

WO2020191239A1 METHODS AND COMPOSITIONS FOR EDITING NUCLEOTIDE SEQUENCES 审中-公开
公开(公告)号：WO2020191239A1
公开(公告)日：2020-09-24
申请号：PCT/US2020/023721
申请日：2020-03-19
申请人： THE BROAD INSTITUTE, INC. , PRESIDENT AND FELLOWS OF HARVARD COLLEGE
发明人： LIU, David, R. , ANZALONE, Andrew, Vito , RANDOLPH, Peyton
IPC分类号： C12N15/11 , C12N9/22 , C12N15/10 , C12N9/12 , C12N15/62
摘要： 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. 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 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 homologous to a strand of the targeted endogenous DNA sequence to be edited, but which contains the desired one or more nucleotide changes and which, following synthesis by the polymerase (e.g., reverse transcriptase), becomes incoporated into the target DNA molecule. Also disclosed herein are various methods that leverage prime editing, including treating trinucleotide repeat contraction diseases, installing targeted peptide tags, treating prion disease through the intallation of protection mutations, manipulating RNA-encoding genes for the installation of RNA tags for controlling the function and expression of RNA, using prime editing to construct sophisticated gene libraries, using prime editing to insert immunoepitopes into proteins, use of prime editing to insert inducible dimerization domains into protein targets, and delivery methods, among others.

78. 发明申请

WO2020191234A1 METHODS AND COMPOSITIONS FOR EDITING NUCLEOTIDE SEQUENCES 审中-公开
公开(公告)号：WO2020191234A1
公开(公告)日：2020-09-24
申请号：PCT/US2020/023713
申请日：2020-03-19
申请人： THE BROAD INSTITUTE, INC. , PRESIDENT AND FELLOWS OF HARVARD COLLEGE
发明人： LIU, David, R. , ANZALONE, Andrew, Vito , RANDOLPH, Peyton , NELSON, James
IPC分类号： C12N15/11 , C12N9/12 , C12N9/22 , C12N15/10 , C07K2319/00 , C07K2319/80 , C07K2319/92 , C12N15/102 , C12N15/1089 , C12N15/111 , C12N15/62 , C12N15/79 , C12N2310/20 , C12N2310/3519 , C12N9/1276 , C12Y207/07049 , C12Y301/00 , G16B20/00 , G16B25/20
摘要： 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. 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 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 homologous to a strand of the targeted endogenous DNA sequence to be edited, but which contains the desired one or more nucleotide changes and which, following synthesis by the polymerase (e.g., reverse transcriptase), becomes incoporated into the target DNA molecule. Also disclosed herein are various methods that leverage prime editing, including treating trinucleotide repeat contraction diseases, installing targeted peptide tags, treating prion disease through the intallation of protection mutations, manipulating RNA-encoding genes for the installation of RNA tags for controlling the function and expression of RNA, using prime editing to construct sophisticated gene libraries, using prime editing to insert immunoepitopes into proteins, use of prime editing to insert inducible dimerization domains into protein targets, and delivery methods, among others.

79. 发明申请

WO2020186231A2 CRISPR EFFECTOR SYSTEM BASED MULTIPLEX DIAGNOSTICS 审中-公开
公开(公告)号：WO2020186231A2
公开(公告)日：2020-09-17
申请号：PCT/US2020/022795
申请日：2020-03-13
申请人： THE BROAD INSTITUTE, INC. , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , PRESIDENT AND FELLOWS OF HARVARD COLLEGE
发明人： GOOTENBERG, Jonathan , ABUDAYYEH, Omar , ZHANG, Feng
摘要： Systems and methods for rapid diagnostics related to the use of CRISPR effector systems and optimized guide sequences, including multiplex lateral flow diagnostic devices and methods of use, are provided.

80. 发明申请

WO2020186223A1 SHERLOCK ASSAYS FOR TICK-BORNE DISEASES 审中-公开
公开(公告)号：WO2020186223A1
公开(公告)日：2020-09-17
申请号：PCT/US2020/022776
申请日：2020-03-13
申请人： THE BROAD INSTITUTE, INC. , PRESIDENT AND FELLOWS OF HARVARD COLLEGE , THE GENERAL HOSPITAL CORPORATION , SABETI, Pardis , ROSENBERG, Eric
发明人： SABETI, Pardis , ROSENBERG, Eric , LEMIEUX, Jacob , ADAMS, Gordon , PIANTADOSI, Anne , NORMANDIN, Erica
IPC分类号： C12Q1/6888 , C12Q1/6844 , B01L3/00
摘要： Provided herein is a nucleic acid detection system comprising a detection CRISPR system having an effector protein and one or more guide RNAs each designed to bind to corresponding target molecules that are diagnostic for a tick-borne disease state; and an RNA-based masking construct. In some embodiments, the detection system of may comprise i) two or more CRISPR systems, each CRISPR system comprising an effector protein and a guide RNA designed to bind to a corresponding target molecule that is diagnostic for a tick-borne disease state; and ii) a set of detection constructs, each detection construct comprising a cutting motif sequence that is preferentially cut by one of the activated CRISPR effector proteins. Exemplary tick-borne detectable microbes include Babesia microti, Anaplasma phagocytophilum, and Borrelia miyamotoi .

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