公开(公告)号：WO2019113457A1

公开(公告)日：2019-06-13

申请号：PCT/US2018/064494

申请日：2018-12-07

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： LOVE, J., Christopher ,  GIERAHN, Todd, Michael ,  SHALEK, Alexander, K. ,  WADSWORTH, Marc, Havens ,  HUGHES, Travis, K.

IPC: B01L3/00 ,  C12Q1/6806 ,  C12N15/10 ,  C12M1/12 ,  G03F7/00

CPC classification number: C12Q1/6874 ,  B01L3/5085 ,  B01L3/50855 ,  B01L2200/0647 ,  B01L2300/0681 ,  B01L2300/0819 ,  B01L2300/0829 ,  B01L2300/0851 ,  C12N15/1068 ,  C12N15/1093 ,  C12N15/1096 ,  C12Q1/6806 ,  G03F7/2014 ,  C12Q2525/15 ,  C12Q2525/155 ,  C12Q2525/191 ,  C12Q2533/101 ,  C12Q2563/179 ,  C12Q2525/173

Abstract: This disclosure describes improvements to both hardware and enzymatic reactions used in single cell analyses such as but not limited to Seq-well that enable significant increases in the yield of transcripts per cell, improved portability and ease of use, increased scalability of the assay, and linkage of transcript information to other measurements made in the picowell arrays.

公开(公告)号：WO2017124101A2

公开(公告)日：2017-07-20

申请号：PCT/US2017/013791

申请日：2017-01-17

Applicant: THE BROAD INSTITUTE INC. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  GIERAHN, Todd M. ,  LOVE, Christopher J. ,  HUGHES, Travis, K. ,  WADSWORTH, Marc, H ,  SHALEK, Alexander, K. ,  CARROLL, Shaina

Inventor： GIERAHN, Todd M. ,  LOVE, Christopher J. ,  HUGHES, Travis, K. ,  WADSWORTH, Marc, H ,  SHALEK, Alexander, K. ,  CARROLL, Shaina

IPC: C12Q1/68

CPC classification number: C12Q1/6874 ,  C12Q2537/143 ,  C12Q2563/149 ,  C12Q2563/179 ,  C12Q2565/514

Abstract: The present application provides a method of assembling a container for one or multiple parallel steps of biochemical analysis on one or more cells comprising performing molecular bonding of a porous membrane on an apical or basal surface of an array having a plurality of wells, wherein the molecular bonding substantially isolates each well from adjacent wells.

Abstract translation: 本申请提供了在一个或多个细胞上组装用于一个或多个平行生物化学分析步骤的容器的方法，包括在阵列的顶端或基底表面上进行多孔膜的分子键合， 多个孔，其中分子结合基本上使每个孔与相邻孔分离。

公开(公告)号：WO2016205728A1

公开(公告)日：2016-12-22

申请号：PCT/US2016/038205

申请日：2016-06-17

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  SHALEK, Alexander, K. ,  GAILLARD, Aleth

Inventor： SHALEK, Alexander, K. ,  GAILLARD, Aleth

IPC: C12N15/63 ,  C12N9/22 ,  C12N15/85 ,  C12N15/90 ,  C12N15/113 ,  C12Q1/68

CPC classification number: C12N15/111 ,  C12N9/22 ,  C12N15/102 ,  C12N15/85 ,  C12N15/907 ,  C12N2310/20 ,  C12N2320/00 ,  C12Q1/68 ,  C12Q2521/301

Abstract: The present invention relates to systems and methods for recording and assaying cellular events, in particular gene expression. The invention provides hereto a method of determining a cellular event of interest in a cell comprising providing a cell comprising a CRISPR-Cas system, wherein the CRISPR-Cas system comprises a guide RNA that targets a selected DNA sequence and a Cas protein capable of modifying the selected DNA sequence; whereby a nucleic acid molecule encoding at least one of the guide RNA or Cas protein is operably connected in the cell with a regulatory element comprising a promoter responsive to the cellular event, and whereby expression of at least one CRISPR-Cas system component is driven by the promoter; and determining cellular event of interest based on detection of the modification of the selected DNA sequence.

Abstract translation: 本发明涉及用于记录和测定细胞事件，特别是基因表达的系统和方法。 本发明提供了确定细胞中感兴趣的细胞事件的方法，包括提供包含CRISPR-Cas系统的细胞，其中CRISPR-Cas系统包含靶向所选DNA序列的引导RNA和能够修饰的Cas蛋白 选择的DNA序列; 其中编码引导RNA或Cas蛋白中的至少一种的核酸分子在细胞中与包含响应于细胞事件的启动子的调节元件可操作地连接，由此表达至少一种CRISPR-Cas系统组分由 启动子; 以及基于所选择的DNA序列的修饰的检测来确定感兴趣的细胞事件。

公开(公告)号：WO2016040476A1

公开(公告)日：2016-03-17

申请号：PCT/US2015/049178

申请日：2015-09-09

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

Inventor： REGEV, Aviv ,  MACOSKO, Evan, Zane ,  MCCARROLL, Steven, Andrew ,  SHALEK, Alexander, K. ,  BASU, Anindita ,  FORD, Christopher, B. ,  PARK, Hongkun ,  WEITZ, David, A.

IPC: C12Q1/68 ,  C12N15/10

CPC classification number: C12Q1/6809 ,  C12N15/1096 ,  C12Q1/6834 ,  C12Q1/6869 ,  G06K19/06 ,  C12Q2521/107 ,  C12Q2525/15 ,  C12Q2525/155 ,  C12Q2525/161 ,  C12Q2525/173 ,  C12Q2563/149 ,  C12Q2563/159 ,  C12Q2565/629 ,  C12Q2563/179

Abstract: The present invention generally relates to a combination of molecular barcoding and emulsion-based microfluidics to isolate, lyse, barcode, and prepare nucleic acids from individual cells in a high-throughput manner.

Abstract translation: 本发明一般涉及以高通量方式分离，裂解，条形码和从各个细胞制备核酸的分子条码和基于乳液的微流体的组合。

公开(公告)号：WO2018170515A1

公开(公告)日：2018-09-20

申请号：PCT/US2018/023170

申请日：2018-03-19

Applicant: THE BROAD INSTITUTE, INC. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  SHALEK, Alexander, K. ,  GENSHAFT, Alexander, S. ,  ZIEGLER, Carly, G.k. ,  VAN HUMBECK, Jeffrey, F. ,  KING, Ryan Philip

Inventor： SHALEK, Alexander, K. ,  GENSHAFT, Alexander, S. ,  ZIEGLER, Carly, G.k. ,  VAN HUMBECK, Jeffrey, F. ,  KING, Ryan Philip

IPC: C12Q1/6837

Abstract: The present invention provides tools and methods for the systematic analysis of genetic interactions between cells. The present invention provides tools and methods for modulating cell phenotypes and compositions, combinatorial probing of cellular circuits, for dissecting cellular circuitry, for delineating molecular pathways, and/or for identifying relevant targets for therapeutics development.

公开(公告)号：WO2017161325A1

公开(公告)日：2017-09-21

申请号：PCT/US2017/023054

申请日：2017-03-17

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  SHALEK, Alexander, K. ,  GENSHAFT, Alexander, S. ,  ZIEGLER, Carly, G., K. ,  VAN HUMBECK, Jeffrey, F.

Inventor： SHALEK, Alexander, K. ,  GENSHAFT, Alexander, S. ,  ZIEGLER, Carly, G., K. ,  VAN HUMBECK, Jeffrey, F.

IPC: C07D231/10 ,  C07H21/00 ,  C07D471/00 ,  C12Q1/68 ,  G01N33/50

CPC classification number: C12Q1/6837 ,  C07D277/04 ,  C07D277/06 ,  C07D493/10 ,  C07D495/04 ,  C07D513/04 ,  C12Q2563/185 ,  C12Q2565/514 ,  C12Q2565/518 ,  G01N33/5005

Abstract: The present invention provides tools and methods for the systematic analysis of genetic interactions between cells. The present invention provides tools and methods for modulating cell phenotypes and compositions, combinatorial probing of cellular circuits, for dissecting cellular circuitry, for delineating molecular pathways, and/or for identifying relevant targets for therapeutics development.

Abstract translation: 本发明提供了用于系统分析细胞之间遗传相互作用的工具和方法。 本发明提供了用于调节细胞表型和组合物，组合探测细胞回路，解剖细胞回路，描绘分子通路和/或鉴定治疗学发展的相关靶标的工具和方法。

公开(公告)号：WO2017124101A3

公开(公告)日：2017-07-20

申请号：PCT/US2017/013791

申请日：2017-01-17

Applicant: THE BROAD INSTITUTE INC. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  GIERAHN, Todd M. ,  LOVE, J. Christopher ,  HUGHES, Travis, K. ,  WADSWORTH II, Marc, H. ,  SHALEK, Alexander, K. ,  CARROLL, Shaina

Inventor： GIERAHN, Todd M. ,  LOVE, J. Christopher ,  HUGHES, Travis, K. ,  WADSWORTH II, Marc, H. ,  SHALEK, Alexander, K. ,  CARROLL, Shaina

IPC: C12Q1/68 ,  G01N35/00

Abstract: The present application provides a method of assembling a container for one or multiple parallel steps of biochemical analysis on one or more cells comprising performing molecular bonding of a porous membrane on an apical or basal surface of an array having a plurality of wells, wherein the molecular bonding substantially isolates each well from adjacent wells.

公开(公告)号：WO2022087526A1

公开(公告)日：2022-04-28

申请号：PCT/US2021/056467

申请日：2021-10-25

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

Inventor： MEAD, Benjamin ,  SHALEK, Alexander, K. ,  KARP, Jeffrey ,  HATTORI, Kazuki

IPC: A61K31/015 ,  A61K31/047 ,  A61K31/706 ,  A61K31/7068 ,  C12N5/071 ,  C12N5/074

Abstract: The subject matter disclosed herein is generally directed to modulation of genes and pathways that drive differentiation of LGR5+ stem cells. The methods and compositions can be used to treat diseases associated with aberrant epithelial barrier function. Using novel screening methods Applicants have identified compounds that increase Paneth cell differentiation. The compounds can be used to treat diseases associated with stem cell differentiation.

公开(公告)号：WO2021081491A2

公开(公告)日：2021-04-29

申请号：PCT/US2020/057342

申请日：2020-10-26

Applicant: DANA-FARBER CANCER INSTITUTE, INC. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： SHALEK, Alexander, K. ,  WINTER, Peter ,  NAVIA, Andrew ,  RAGHAVAN, Srivatsan ,  HAHN, William ,  AGUIRRE, Andrew ,  WOLPIN, Brian ,  GALVEZ-REYES, Jennyfer

IPC: A61K35/17 ,  C12N5/071 ,  C12Q1/6869 ,  C12N5/00 ,  C12Q1/6886

Abstract: In certain example embodiments, the invention provides a method of generating an ex vivo cell-based system comprising dissociating an original tissue sample obtained from a subject into a single cell population; determining an in vivo phenotype of the tissue sample by conducting single-cell RNA analysis on a first portion of the single cells; establishing an ex vivo cell-based system from a second portion of the single cells; and culturing the ex vivo cell-based system in a medium or conditions selected to maintain the in vivo phenotype. In some embodiments, the original tissue sample is a tumor tissue sample, such as a pancreatic ductal adenocarcinoma (PDAC) tumor sample.

公开(公告)号：WO2019232542A3

公开(公告)日：2019-12-05

申请号：PCT/US2019/035252

申请日：2019-06-03

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  THE GENERAL HOSPITAL CORPORATION ,  DANA-FARBER CANCER INSTITUTE, INC. ,  BRASTIANOS, Kaliopi, Priscilla ,  ALVAREZ-BRECKENRIDGE, Christopher, Allen

Inventor： BRASTIANOS, Kaliopi, Priscilla ,  ALVAREZ-BRECKENRIDGE, Christopher, Allen ,  SHALEK, Alexander, K. ,  CARTER, Scott ,  PRAKADAN, Sanjay

IPC: C12Q1/6886

Abstract: The subject matter disclosed herein is generally directed to detecting and modulating novel gene signatures for the treatment and prognosis of cancer. The gene signatures can be detected in samples obtained from the extracellular fluid of a subject suffering from cancer. The novel gene signatures can be used to predict and monitor responses to immunotherapy in cancer and can be targeted therapeutically. The immunotherapy can be immune checkpoint inhibition therapy.