Abstract: The present disclosure provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides mutated Cas13 proteins and their use in modifying target sequences as well as mutated Cas13 nucleic acid sequences and vectors encoding mutated Cas13 proteins and vector systems or CRISPR-Cas13 systems.
Type:
Application
Filed:
July 31, 2019
Publication date:
November 17, 2022
Applicants:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Feng Zhang, Ian Slaymaker, Soumya Kannan, Jonathan Gootenberg, Omar Abudayyeh
Abstract: The present invention relates to compositions and methods for targeting cancer-specific DNA sequences, such as copy number amplifications and other types of cancer-specific sequence variations, such as cancer-specific polymorphisms, insertions, or deletions. The present invention provides hereto sequence-specific DNA targeting agents targeting a sequence within the amplified DNA region or a sequence otherwise specific for a cancer cell compared to a non-cancer cell. The invention further relates to methods for treating cancer, comprising administering such sequence-specific DNA targeting agents. The invention further relates to methods for preparing sequence-specific DNA targeting agent, as well as screening methods using the DNA targeting agents.
Type:
Grant
Filed:
October 20, 2016
Date of Patent:
November 8, 2022
Assignees:
THE BROAD INSTITUTE INC., DANA-FARBER CANCER INSTITUTE, INC., INSTITUTO CARLOS SLIM DE LA SALUD, A.C.
Inventors:
William C. Hahn, Andrew Aguirre, April Cook, Glenn Cowley, Robin Meyers, David E. Root, Aviad Tsherniak, Barbara Weir, Francisca Vazquez
Abstract: The present disclosure relates to compositions and methods for rapid prediction, based upon early single cell transcriptomic assessment of a biopsied sample obtained from a subject, of whether a subject will be responsive to a drug.
Type:
Application
Filed:
September 1, 2020
Publication date:
October 27, 2022
Applicants:
THE BROAD INSTITUTE, INC., DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Andrew J. Aguirre, Francisca Vazquez, Aviad Tsherniak, James McFarland, Brenton Paolella
Abstract: An engineered system for modulating a nucleic acid molecule. In some examples, the system comprises a programmable inducer of DNA damage; one or more functional domain such as a reverse transcriptase domain, topoisomerase domain and/or polymerase domain; a recombination enhancer domain; and an RNA template encoding a donor polynucleotide and capable of forming a complex with the RT domain.
Type:
Application
Filed:
September 28, 2020
Publication date:
October 27, 2022
Applicants:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventors:
Feng Zhang, Jonathan Schmid-Burgk, Suchita Nety
Abstract: The invention provides methods of using low coverage sequencing to assess the relative fraction of tumor versus normal DNA in a sample, and to assess copy number alterations present in the sample.
Type:
Grant
Filed:
March 16, 2017
Date of Patent:
October 25, 2022
Assignees:
DANA-FARBER CANCER INSTITUTE, INC., THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Gavin Ha, Viktor Adalsteinsson, Samuel Freeman
Abstract: 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, including for detection of cancer markers, are provided.
Type:
Application
Filed:
September 3, 2020
Publication date:
October 20, 2022
Applicants:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, DANA-FARBER CANCER INSTITUTE, INC.
Inventors:
Jonathan Gootenberg, Omar Abudayyeh, Jeremy Koob, Rahul Vedula, Coleman Lindsley, Feng Zhang
Abstract: The invention features compositions and methods that are useful for increasing the level or activity of SLC16A11 in a subject, there by treating or preventing type 2 diabetes in the subject.
Type:
Grant
Filed:
June 27, 2017
Date of Patent:
October 18, 2022
Assignees:
THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Eitan Hoch, Suzanne Beth Rosenberg Jacobs, Victor Rusu, Liping Zhao, Jose M. Mercader Bigas
Abstract: Systems and methods for rapid diagnostics related to the use of CRISPR effector systems and optimized guide sequences for detection of coronavirus, including multiplex lateral flow diagnostic devices and methods of use, are provided.
Type:
Application
Filed:
April 27, 2022
Publication date:
October 13, 2022
Applicants:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventors:
Feng Zhang, Jonathan Gootenberg, Omar Abudayyeh, Julia Joung, Alim Ladha, Han Altae-Tran, Guilhem Faure
Abstract: The present disclosure relates to compositions and methods that enable enhanced monitoring and improvement of heterologous ribosome activity within a host cell. Specifically, the instant disclosure provides a reporter system that allows for improved monitoring of heterologous ribosome activity in a host cell, via engineering of both heterologous rRNA operon sequences and reporter operon sequences. New transgenic organisms harboring heterologous ribosome operons are also provided, as are methods for identifying agents capable of targeting heterologous ribosomes (e.g., ribosomes of pathogenic organisms, optionally selectively as compared to ribosomes of, e.g., commensal organisms) within a host cell.
Abstract: The present disclosure relates to antimicrobial compositions, particularly to antibiotic compositions; to methods for identification of antimicrobial compositions involving in silico prediction of antimicrobial activity; and to use of antimicrobial compositions and methods.
Type:
Application
Filed:
September 9, 2020
Publication date:
September 29, 2022
Applicants:
MASSACHUSETTS INSTITUTE OF TECHOLOGY, THE BROAD INSTITUTE, INC.
Inventors:
James Collins, Regina Barzilay, Jonathan Stokes, Ian Andrews, Daniel Collins
Abstract: Systems and methods for rapid diagnostics related to the use of CRISPR effector systems and optimized guide sequences for detection of coronavirus, including multiplex lateral flow diagnostic devices and methods of use, are provided.
Type:
Grant
Filed:
June 5, 2020
Date of Patent:
September 27, 2022
Assignees:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventors:
Feng Zhang, Jonathan Gootenberg, Omar Abudayyeh, Julia Joung, Alim Ladha, Han Altae-Tran, Guilhem Faure
Abstract: Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) systems and transposable elements.
Type:
Application
Filed:
August 28, 2020
Publication date:
September 22, 2022
Applicants:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventors:
Feng Zhang, Han Altae-Tran, Soumya Kannan
Abstract: The present disclosure relates to method of distinguishing between two or more species of one or more organisms in a sample, by contacting a biological sample comprising ribosomal ribonucleic acid (rRNA) with a set of antisense probes, wherein the set of probes contains at least one detectable probe that is specific for a target rRNA sequence of each species to be tested, and wherein the individual probes specific for each species comprises less than about 85% sequence identity; and, detecting hybridization between one or more of the probes and the rRNA, thereby distinguishing between two or more species in a sample.
Type:
Grant
Filed:
March 14, 2014
Date of Patent:
September 13, 2022
Assignees:
THE BROAD INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION
Inventors:
Roby Bhattacharyya, Deborah Hung, Jonathan Livny
Abstract: Embodiments disclosed herein provide reagents and methods for high-throughput screening of nucleic acid sequence variations in nucleic acid containing specimens. Nucleic acid specimens to be screened are loaded into separate discrete volumes. Optically encoded particles are used to deliver primers to amplify one or more sequences comprising the nucleic acid sequence variation. The optically encoded particles may be delivered to the discrete volumes randomly resulting in a random combination of optically encoded particles in each well, or a unique combination of optically encoded particles may be specifically assigned to each discrete volume. The observable combination of optically encoded particles may then be used to identify each discrete volume.
Type:
Grant
Filed:
August 25, 2016
Date of Patent:
August 23, 2022
Assignees:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventors:
David Feldman, Daniel Sazer, Paul Blainey
Abstract: Provided herein are methods for generating single-cell molecular analysis comprising a) delivering one or more proximity dependent probes to a cell population, wherein each proximity dependent probe comprises a target binding region configured to bind a target RNA and a primer binding site region; b) linking bound proximity dependent probes; c) isolating single cells from the cell population in separate individual discrete volumes, the individual discrete volumes further comprising a primer pair and amplification reagents, wherein the primer pair binds to the primer binding sites of the ligation dependent probes, and wherein at least one primer comprises a barcode sequence that uniquely identifies the individual discrete volume; d) amplifying the ligated probes using the primer pair, wherein the barcode is incorporated into each resulting amplicon; and e) quantifying target RNAs in each individual cell based at least in part on sequencing the resulting amplicons.
Type:
Grant
Filed:
May 24, 2019
Date of Patent:
August 16, 2022
Assignees:
THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE, MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Abstract: The specification relates generally to methods of detecting, diagnosing, and/or identifying pathogens, e.g., infectious disease pathogens and determining their drug sensitivity and appropriate methods of treatment. This invention also relates generally to methods of monitoring pathogen infection in individual subjects as well as larger populations of subjects.
Type:
Application
Filed:
April 21, 2022
Publication date:
August 11, 2022
Applicants:
THE BROAD INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION
Abstract: 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.
Type:
Grant
Filed:
June 10, 2016
Date of Patent:
August 9, 2022
Assignees:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventors:
Le Cong, David Benjamin Turitz Cox, Matthias Heidenreich, Randall Jeffrey Platt, Lukasz Swiech, Feng Zhang
Abstract: Described in certain example embodiments herein are highly sensitive systems and methods of amplifying RNA in a sample. In certain example embodiments, the method includes reverse transcribing one or more strands of template RNA in the sample into a first cDNA strand in the presence of a first primer comprising a unique molecular identifier (UMI), a second primer comprising a T7 promoter sequence, and a reverse transcriptase enzyme; synthesizing a second cDNA strand in the presence of a DNA polymerase to generate double-stranded cDNA; and transcribing the double-stranded cDNA in the presence of a T7 RNA polymerase to generate amplified RNA. The systems and methods described herein allow for amplification from very small amounts of template RNA, in some embodiments, as little as 0.5 picograms.
Type:
Application
Filed:
November 23, 2021
Publication date:
August 4, 2022
Applicants:
THE BROAD INSTITUTE, INC., THE GENERAL HOSPITAL CORPORATION
Abstract: The disclosure provides for systems, methods, and compositions for targeting polynucleotides. More particularly, the disclosure provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA and wherein the CRISPR effector protein is a Cas protein.
Type:
Application
Filed:
May 20, 2020
Publication date:
July 28, 2022
Applicants:
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Abstract: The present disclosure relates to methods aimed towards non-invasive targeted genomic and epigenomic sequencing of spatially-defined cellular or subcellular region. More particularly, the present disclosure relates to methods of using photoselection to achieve non-invasive targeted genomic and epigenomic sequencing of spatially-defined cellular or subcellular regions, via the use of light-activated probes.
Type:
Application
Filed:
January 24, 2022
Publication date:
July 28, 2022
Applicants:
THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE