公开(公告)号：US20210207203A1

公开(公告)日：2021-07-08

申请号：US17254886

申请日：2019-06-26

申请人： THE BROAD INSTITUTE, INC. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  PRESIDENT AND FELLOWS OF HARVARD COLLEGE

发明人： Feng Zhang ,  Max Kellner ,  Jonathan Gootenberg ,  Omar Abudayyeh

IPC分类号： C12Q1/6844 ,  C12N15/113 ,  C12N9/22

摘要： The embodiments disclosed herein utilized RNA targeting effectors to provide robust CRISPR-based nucleic acid amplification methods and systems. Embodiments disclosed herein can amplify both double-stranded and single-stranded nucleic acid targets. Moreover, the embodiments disclosed herein can be combined with various detection platforms, for example, CRISPR-SHERLOCK, to achieve detection and diagnostic with attomolar sensitivity. 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.

公开(公告)号：US20210009972A1

公开(公告)日：2021-01-14

申请号：US16650480

申请日：2018-10-04

申请人： THE BROAD INSTITUTE, INC. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  PRESIDENT AND FELLOWS OF HARVARD COLLEGE

发明人： Feng Zhang ,  Jonathan Gootenberg ,  Omar Abudayyeh

IPC分类号： C12N9/22 ,  C12N15/113 ,  C12N9/78 ,  C12N15/86

摘要： The invention provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the invention provides non-naturally occurring or engineered RNA-targeting systems comprising a RNA-targeting Cas13 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.

公开(公告)号：US20200291115A1

公开(公告)日：2020-09-17

申请号：US16819778

申请日：2020-03-16

申请人： THE BROAD INSTITUTE, INC. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY

发明人： Feng Zhang

IPC分类号： C07K16/28 ,  C07K16/44 ,  A61K35/17

摘要： An engineered, non-naturally occurring molecule for target immunotherapy, comprising: (a) a first binding component capable of binding to a T cell; and (b) a second binding component capable of binding to a diseased cell.

公开(公告)号：US10655173B2

公开(公告)日：2020-05-19

申请号：US15030154

申请日：2014-10-17

申请人： THE BROAD INSTITUTE, INC. ,  Massachusetts Institute of Technology

发明人： Feng Zhang ,  Joshua Asher Weinstein ,  Aviv Regev

IPC分类号： C12Q1/6874 ,  C12Q1/6844

摘要： The present invention relates to molecular microscopy or volumetric imaging by proximal unique molecular identifiers (“UID”) reaction (“VIPUR”) microscopy methods to record the cellular co-localization and/or spatial distributions of arbitrary nucleic acid sequences, or other biomolecules tagged with nucleic sequences. The method involves one or both of two DNA sequence-components such as an α-UID, which may identify the targeted sequences-of-interest themselves and/or spatial beacons relative to which their distances are measured, and a- β-UID, which labels α-UID association events.

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

发明人： Feng Zhang ,  Bernd Zetsche ,  Jonathan S. Gootenberg ,  Omar O Abudayyeh ,  Ian Slaymaker

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.

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.

公开(公告)号：US20190330605A1

公开(公告)日：2019-10-31

申请号：US16459174

申请日：2019-07-01

申请人： The Broad Institute, Inc. ,  Massachusetts Institute of Technology

发明人： Feng Zhang ,  Bernd Zetsche

IPC分类号： C12N9/22 ,  C12N15/79 ,  C12N15/90 ,  C12N15/63 ,  C12N15/10

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.

公开(公告)号：US20190300581A1

公开(公告)日：2019-10-03

申请号：US16374670

申请日：2019-04-03

申请人： The Broad Institute, Inc. ,  Massachusetts Institute of Technology

发明人： Feng Zhang

IPC分类号： C07K14/24 ,  C12N15/10 ,  C12N15/86

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.

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.

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

IPC分类号： C12N15/63 ,  C12N15/62 ,  C12N15/86

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.