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公开(公告)号：US10648020B2
公开(公告)日：2020-05-12
申请号：US15844608
申请日：2017-12-17
申请人： The Broad Institute Inc. , Massachusetts Institute of Technology , President and Fellows of Harvard College
IPC分类号： C12Q1/6832 , C12N15/11 , C12N9/22 , C12N15/113 , C12Q1/6816
摘要： 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.
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32.发明授权公开(公告)号：US10577630B2
公开(公告)日：2020-03-03
申请号：US14971356
申请日：2015-12-16
申请人： The Broad Institute, Inc. , Massachusetts Institute of Technology , President and Fellows of Harvard College
发明人： Feng Zhang , Le Cong , Fei Ran
IPC分类号： A01K67/00 , C12N15/90 , C12N9/22 , C12N15/63 , C12N15/10 , A01K67/027 , C12N15/86 , A61K48/00 , C12N7/00
摘要： The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.
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33.发明申请公开(公告)号：US20190330605A1
公开(公告)日：2019-10-31
申请号：US16459174
申请日：2019-07-01
发明人： Feng Zhang , Bernd Zetsche
摘要： 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 the engineering of optimized modular CRISPR-Cas enzyme systems.
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公开(公告)号：US20190300581A1
公开(公告)日：2019-10-03
申请号：US16374670
申请日：2019-04-03
发明人： Feng Zhang
摘要： The disclosure provides novel programmable targeting sequences and applications thereof. The targeting sequences can be engineered for binding to proteins, polypeptides, and other macromolecules.
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35.发明申请公开(公告)号：US20190218276A1
公开(公告)日：2019-07-18
申请号：US16087036
申请日：2016-10-27
申请人： THE BROAD INSTITUTE, INC. , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , PRESIDENT AND FELLOWS OF HARVARD COLLEGE
发明人： Aviv Regev , Feng Zhang , Naomi Habib , Yinqing Li , Matthias Heidenreich , Lukasz Swiech , Anindita Basu , David Weitz , Inbal Avraham Davidi
IPC分类号： C07K16/10 , C12N15/10 , C12Q1/686 , C12Q1/6869
CPC分类号： C07K16/1036 , C12N15/1093 , C12N15/1096 , C12Q1/686 , C12Q1/6869 , C12Q2537/165 , C12Q2563/179 , C12Q2565/514 , C12Q2565/629
摘要： Transcriptomes of individual neurons provide rich information about cell types and dynamic states. However, it is difficult to capture rare dynamic processes, such as adult neurogenesis, because isolation from dense adult tissue is challenging, and markers for each phase are limited. Here, Applicants developed Nuc-seq, Div-Seq, and Dronc-Seq. Div-seq combines Nuc-Seq, a scalable single nucleus RNA-Seq method, with EdU-mediated labeling of proliferating cells. Nuc-Seq can sensitively identify closely related cell types within the adult hippocampus. Div-Seq can track transcriptional dynamics of newborn neurons in an adult neurogenic region in the hippocampus. Dronc-Seq uses a microfluidic device to co-encapsulate individual nuclei in reverse emulsion aqueous droplets in an oil medium together with one uniquely barcoded mRNA-capture bead. Finally, Applicants found rare adult newborn GABAergic neurons in the spinal cord, a non-canonical neurogenic region. Taken together, Nuc-Seq, Div-Seq and Dronc-Seq allow for unbiased analysis of any complex tissue.
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36.发明申请公开(公告)号：US20190203212A1
公开(公告)日：2019-07-04
申请号：US16297560
申请日：2019-03-08
申请人： Massachusetts Institute of Technology , The Broad Institute, Inc. , President and Fellows of Harvard College
发明人： Feng Zhang , Mark Brigham , Le Cong , Silvana Konermann , Neville Sanjana
CPC分类号： C12N15/635 , C12N15/62 , C12N15/63 , C12N15/86 , C12N2740/16043 , C12N2750/14143
摘要： The present invention generally relates to methods and compositions used for the spatial and temporal control of gene expression that may use inducible transcriptional effectors. The invention particularly relates to inducible methods of altering or perturbing expression of a genomic locus of interest in a cell wherein the genomic locus may be contacted with a non-naturally occurring or engineered composition comprising a deoxyribonucleic acid (DNA) binding polypeptide.
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公开(公告)号：US10266887B2
公开(公告)日：2019-04-23
申请号：US15917549
申请日：2018-03-09
申请人： THE BROAD INSTITUTE, INC. , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , PRESIDENT AND FELLOWS OF HARVARD COLLEGE
IPC分类号： C12Q1/6809 , C12Q1/6811 , C12Q1/6876 , C12N15/113 , C12Q1/6869 , C12Q1/6806 , C12P19/34 , C12Q1/6816 , C12N9/22 , G01N33/00 , C12Q1/68
摘要： The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.
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公开(公告)号：US20190017058A1
公开(公告)日：2019-01-17
申请号：US15967495
申请日：2018-04-30
申请人： THE BROAD INSTITUTE INC. , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , PRESIDENT AND FELLOWS OF HARVARD COLLEGE
发明人： Feng Zhang , Le CONG , David Benjamin Turitz COX , Patrick HSU , Shuailiang LIN , Fei RAN , Randall Jeffrey PLATT , Neville Espi SANJANA
IPC分类号： C12N15/74 , C12N9/22 , C12N15/113 , C12N15/63 , C12N15/70 , C12N15/85 , C12N15/90 , C12N15/10
摘要： The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/CAS system.
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公开(公告)号：US20190010471A1
公开(公告)日：2019-01-10
申请号：US15844528
申请日：2017-12-16
发明人： Feng Zhang , Linyi Gao , Bernd Zetsche , Ian Slaymaker
摘要： Disclosed and claimed are mutation(s) or modification(s) of the CRISPR enzyme, for example a Cas enzyme such as a Cas9, which obtain an improvement, for instance a reduction, as to off-target effects of a CRISPR-Cas or CRISPR-enzyme or CRISPR-Cas9 system or complex containing or including such a mutated or modified Cas or CRISPR enzyme or Cas9. Methods for making and using and uses of such mutated or modified Cas or CRISPR enzyme or Cas9 and systems or complexes containing the same and products from such methods and uses are also disclosed and claimed.
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公开(公告)号：US20180305704A1
公开(公告)日：2018-10-25
申请号：US15838064
申请日：2017-12-11
发明人： Feng Zhang
IPC分类号： C12N15/74 , C12N9/22 , C12N15/113 , C12N15/63 , C12N15/70 , C12N15/85 , C12N15/90 , C12N15/10
CPC分类号： C12N15/746 , C12N9/22 , C12N15/102 , C12N15/1082 , C12N15/113 , C12N15/63 , C12N15/70 , C12N15/74 , C12N15/85 , C12N15/8509 , C12N15/907 , C12N2310/20 , C12N2310/3519 , C12N2310/531 , C12N2800/101
摘要： The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.
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