Patents by Inventor Bradley E. Bernstein
Bradley E. Bernstein has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
-
Patent number: 11891631Abstract: Fusion proteins comprising a DNA binding domain, e.g., a TAL effector repeat array (TALE) or zinc finger array, and a catalytic domain comprising a sequence that catalyzes histone demethylation, and methods of use thereof.Type: GrantFiled: April 5, 2019Date of Patent: February 6, 2024Assignee: The General Hospital CorporationInventors: Jae Keith Joung, Eric M. Mendenhall, Bradley E. Bernstein, Deepak Reyon
-
Publication number: 20210355535Abstract: The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“CUP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation.Type: ApplicationFiled: May 25, 2021Publication date: November 18, 2021Applicants: President and Fellows of Harvard College, The General Hospital CorporationInventors: David Weitz, Assaf Rotem, Oren Ram, Bradley E. Bernstein
-
Publication number: 20210308171Abstract: CRISPR-Cas9 has enabled a new generation of screening strategies to interrogate gene function. However, redundant genes and the complexity of functional gene networks can confound single gene knockout approaches. Furthermore, simple addition of two or more sgRNAs has shown only modest targeting efficacy in screening approaches. The present invention relates to combined orthogonal CRISPR-derived components to maximize gene targeting activity with minimal cross-talk and interference. The present invention also relates to efficient S. aureus Cas9 sgRNA design rules, which were paired with S. pyogenes Cas9 sgRNA design rules to achieve dual target gene inactivation in a high fraction of cells. Applicants developed a lentiviral vector and cloning strategy to generate high complexity pooled dual-knockout libraries and show that screening these libraries can identify combinatorial phenotypes, including synthetic lethal gene pairs across multiple cell types.Type: ApplicationFiled: August 7, 2019Publication date: October 7, 2021Inventors: Bradley E. BERNSTEIN, John G. DOENCH, Fadi J. NAJM
-
Patent number: 11047003Abstract: The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“ChIP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation.Type: GrantFiled: August 7, 2017Date of Patent: June 29, 2021Assignees: The General Hospital Corporation, President and Fellows of Harvard CollegeInventors: Assaf Rotem, Oren Ram, Bradley E. Bernstein, David A. Weitz
-
Patent number: 11001883Abstract: The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“ChIP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation.Type: GrantFiled: September 5, 2014Date of Patent: May 11, 2021Assignees: The General Hospital Corporation, President and Fellows of Harvard CollegeInventors: Assaf Rotem, Oren Ram, Bradley E. Bernstein, David A. Weitz
-
Publication number: 20190359951Abstract: Fusion proteins comprising a DNA binding domain, e.g., a TAL effector repeat array (TALE) or zinc finger array, and a catalytic domain comprising a sequence that catalyzes histone demethylation, and methods of use thereof.Type: ApplicationFiled: April 5, 2019Publication date: November 28, 2019Inventors: Jae Keith Joung, Eric M. Mendenhall, Bradley E. Bernstein, Deepak Reyon
-
Patent number: 10479986Abstract: Embodiments disclosed herein provide methods for identifying cell-type-specific nucleosomal DNA modifications. The methods leverage nucleosomal DNA barcoding and pool-and-split multiplexing to provide high-throughout, quantitative profiling of nucleosomal DNA states. The methods enable the profiling of multiple nucleosomal DNA marks across different cell types and/or conditions thereby linking quantitative changes in chromatin landscapes to different genotypes and chemical and physical perturbations.Type: GrantFiled: May 26, 2017Date of Patent: November 19, 2019Assignees: The Broad Institute, Inc., The General Hospital CorporationInventors: Charles B. Epstein, Peter Van Galen, Bradley E. Bernstein
-
Publication number: 20190185559Abstract: The invention provides therapeutic combinations comprising an agent that inhibits Notch signaling and an agent that inhibits B cell receptor signaling, and methods of using such agents to inhibit the survival or proliferation of a neoplastic cell.Type: ApplicationFiled: September 1, 2017Publication date: June 20, 2019Applicants: THE BRIGHAM AND WOMEN'S HOSPITAL, INC., THE GENERAL HOSPITAL CORPORATION, THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIAInventors: RYAN J.H. RUSSELL, BRADLEY E. BERNSTEIN, JON ASTER, WARREN S. PEAR
-
Publication number: 20190000831Abstract: The present invention provides compositions and methods for the treatment of drug-tolerant glioblastoma, and in particular glioblastoma stem cells. Specifically, the methods comprise contacting a glioblastoma stem cell with a platelet-derived growth factor receptor alpha inhibitor and one or more of a histone lysine demethylase inhibitor and a Notch inhibitor.Type: ApplicationFiled: March 24, 2016Publication date: January 3, 2019Applicant: THE GENERAL HOSPITAL CORPORATIONInventors: BRIAN B. LIAU, ANOOP P. PATEL, CEM SIEVERS, BRADLEY E. BERNSTEIN
-
Publication number: 20180265922Abstract: The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“ChIP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation.Type: ApplicationFiled: April 27, 2018Publication date: September 20, 2018Inventors: David A. Weitz, Assaf Rotem, Oren Ram, Bradley E. Bernstein
-
Publication number: 20180155777Abstract: The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“ChIP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation.Type: ApplicationFiled: December 8, 2017Publication date: June 7, 2018Inventors: David A. Weitz, Assaf Rotem, Oren Ram, Bradley E. Bernstein
-
Publication number: 20180155778Abstract: The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“ChIP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation.Type: ApplicationFiled: December 8, 2017Publication date: June 7, 2018Inventors: David A. Weitz, Assaf Rotem, Oren Ram, Bradley E. Bernstein
-
Publication number: 20180023133Abstract: The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“ChIP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation.Type: ApplicationFiled: August 7, 2017Publication date: January 25, 2018Inventors: Assaf Rotem, Oren Ram, Bradley E. Bernstein, David A. Weitz
-
Publication number: 20170343539Abstract: Embodiments disclosed herein provide methods for identifying cell-type-specific nucleosomal DNA modifications. The methods leverage nucleosomal DNA barcoding and pool-and-split multiplexing to provide high-throughout, quantitative profiling of nucleosomal DNA states.Type: ApplicationFiled: May 26, 2017Publication date: November 30, 2017Inventors: Charles B. EPSTEIN, Peter VAN GALEN, Bradley E. BERNSTEIN
-
Patent number: 9763956Abstract: The invention relates to methods of treatment and diagnosis of subjects with cancer. In some aspects, the invention relates to methods of treatment and diagnosis of subjects with cancer, wherein the cancer is characterized by a Notch pathway activation mutation or by resistance to a Notch pathway inhibitor.Type: GrantFiled: June 19, 2013Date of Patent: September 19, 2017Assignees: The Broad Institute, Inc., The Brigham and Women's Hospital, Inc., The General Hospital Corporation, Dana-Farber Cancer Institute, Inc.Inventors: Bradley E. Bernstein, Jon C. Aster, James E. Bradner, Birgit Knoechel, Christopher J. Ott, David Root
-
Patent number: 9631226Abstract: Control agents for immunoprecipitation assays, methods of using the control agents and kits comprising the control agents are provided.Type: GrantFiled: September 16, 2015Date of Patent: April 25, 2017Assignee: The General Hospital CorporationInventors: Bradley E. Bernstein, Alon Goren
-
Publication number: 20170028377Abstract: The present invention generally relates to microfluidic devices, including systems and methods for tagging droplets within such devices. In some aspects, microfluidic droplets are manipulated by exposing the droplets (or other discrete entities) to a variety of different conditions. By incorporating into the droplets a plurality of nucleic acid “tags,” and optionally ligating then nucleic acids together, the conditions that a droplet was exposed to may be encoded by the nucleic acid tags. Thus, even if droplets exposed to different conditions are mixed together, the conditions that each droplet encountered may still be determined, for example, by sequencing the nucleic acids.Type: ApplicationFiled: April 17, 2015Publication date: February 2, 2017Inventors: Bradley E. Bernstein, Robert Nicol, David A. Weitz
-
Publication number: 20160116474Abstract: The present invention provides compositions and methods for the diagnosis and treatment of glioblastoma, particularly tumor propagating cells within the glioblastoma.Type: ApplicationFiled: June 19, 2014Publication date: April 28, 2016Applicants: THE BROAD INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATIONInventors: MARIO L. SUVA, ESTHER RHEINBAY, ANOOP P. PATEL, BRADLEY E. BERNSTEIN
-
Publication number: 20160068885Abstract: Control agents for immunoprecipitation assays, methods of using the control agents and kits comprising the control agents are provided.Type: ApplicationFiled: September 16, 2015Publication date: March 10, 2016Applicant: The General Hospital Corporation d/b/a Massachusetts General HospitalInventors: Bradley E. Bernstein, Alon Goren
-
Patent number: 9175043Abstract: Control agents for immuno-precipitation assays, methods of using the control agents and kits comprising the control agents are provided.Type: GrantFiled: March 29, 2013Date of Patent: November 3, 2015Assignee: The General Hospital CorporationInventors: Bradley E. Bernstein, Alon Goren