Patents Assigned to BROAD INSTITUTE
  • Publication number: 20200347100
    Abstract: Provided herein are non-naturally occurring self-assembling polypeptides for transferring nucleic acids and/or proteins to a cell, pharmaceutical compositions comprising such polypeptides, and methods for treatment comprising use of such compositions. The methods for producing polypeptide compositions may include combining in a solution, unassembled recombinant GAG-like proteins, nucleic acids and/or proteins in low salt conditions; and increasing the ionic strength of the solution.
    Type: Application
    Filed: March 16, 2020
    Publication date: November 5, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventor: Feng Zhang
  • Publication number: 20200347444
    Abstract: The present invention provides compositions and methods for making and using a transcriptome-wide gene-expression profiling platform that measures the expression levels of only a select subset of the total number of transcripts. Because gene expression is believed to be highly correlated, direct measurement of a small number (for example, 1,000) of appropriately-selected transcripts allows the expression levels of the remainder to be inferred. The present invention, therefore, has the potential to reduce the cost and increase the throughput of full-transcriptome gene-expression profiling relative to the well-known conventional approaches that require all transcripts to be measured.
    Type: Application
    Filed: February 18, 2020
    Publication date: November 5, 2020
    Applicants: MASSACHUSETTS INSTITUTE OF TECHNOLOGY, DANA-FARBER CANCER INSTITUTE, INC., THE BROAD INSTITUTE, INC.
    Inventors: JUSTIN LAMB, TODD R. GOLUB, ARAVIND SUBRAMANIAN, DAVID D. PECK
  • Publication number: 20200340015
    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 particle formulations and/or systems comprising one or more components of a CRISPR-Cas system, which are means for targeting sites for delivery. The delivery particle formulations of the invention are preferably nanoparticle delivery formulations and/or systems. 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: Application
    Filed: July 6, 2020
    Publication date: October 29, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: James DAHLMAN, Randall Jeffrey PLATT, Daniel G. ANDERSON, Robert S. LANGER, Feng ZHANG
  • Patent number: 10816547
    Abstract: The present invention relates to compositions which may comprise a non-naturally occurring or engineered artificial transcription factor, wherein the transcription factor may comprise a sequence specific DNA binding domain, a sliding domain, and one or more linkers, wherein the DNA binding domain and the sliding domain are operably connected by the one or more linkers, and uses thereof. Methods involving the use of a non-naturally occurring or engineered artificial transcription factors and pharmaceutical compositions, methods for treating cancer, a degenerative disease, a genetic disease or an infectious disease as well as diagnostic methods are also contemplated by the present invention.
    Type: Grant
    Filed: April 14, 2016
    Date of Patent: October 27, 2020
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Paul Blainey, Anthony Kulesa, Kan Xiong
  • Patent number: 10815215
    Abstract: The present invention provides triazolone compounds of general formula (I): in which R1, R2, R3, R4 and R5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.
    Type: Grant
    Filed: October 25, 2017
    Date of Patent: October 27, 2020
    Assignees: BAYER AKTIENGESELLSCHAFT, BAYER PHARMA AKTIENGELLSCHAFT, THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE, THE GENERAL HOSPITAL CORPORATION
    Inventors: Stefan Nikolaus Gradl, Duy Nguyen, Knut Eis, Judith Günther, Timo Stellfeld, Andreas Janzer, Sven Christian, Thomas Müller, Sherif El Sheikh, Han Jie Zhou, Changjia Zhao, David B. Sykes, Steven James Ferrara, Kery Liu, Michael Kröber, Claudia Merz, Michael Niehues, Martina Schäfer, Katja Zimmermann, Carl Friedrich Nising
  • Publication number: 20200332272
    Abstract: The present disclosure provides methods for inhibiting intra and inter-cellular signaling pathways by modification of post-translation modification sites on select target RNA molecules. In certain example embodiments, the present disclosure provides methods for inhibiting intracellular phosphorylation of serine, threonine and tyrosine residues by editing the genetic codon of these amino acids by means of site-directed RNA editing or RNA molecules. Embodiments disclosed herein further provide methods of inhibiting pathological activation of cell signaling meditated by post-translational modifications, such as phosphorylation, which are involved in many diseases, including cancer, immunodeficiency, infectious diseases, inflammatory disorders and neurodegenerative disorders.
    Type: Application
    Filed: October 23, 2018
    Publication date: October 22, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Mohammad Pirmoradian Najafabadi, Qiang Pan-Hammarström, Jonathan Gootenberg, David Benjamin Turitz Cox, Omar Abudayyeh
  • Patent number: 10801017
    Abstract: The invention relates to methods of altering expression of a genomic locus of interest or specifically targeting a genomic locus of interest in an animal cell, which may involve contacting the genomic locus with a non-naturally occurring or engineered composition that includes a deoxyribonucleic acid (DNA) binding polypeptide having a N-terminal capping region, a DNA binding domain comprising at least five or more Transcription activator-like effector (TALE) monomers and at least one or more half-monomers specifically ordered to target the genomic locus of interest, and a C-terminal capping region, wherein the polypeptide includes at least one or more effector domains, and wherein the polypeptide is encoded by and translated from a codon optimized nucleic acid molecule so that the polypeptide preferentially binds to the DNA of the genomic locus.
    Type: Grant
    Filed: May 30, 2014
    Date of Patent: October 13, 2020
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Le Cong, Sam Locascio
  • Publication number: 20200308604
    Abstract: Disclosed herein are methods and compositions useful in targeting a payload to, or editing a target nucleic acid, where a governing gRNA molecule is used to target, optionally inactivate, a Cas9 molecule or a Cas9 molecule/gRNA complex.
    Type: Application
    Filed: March 31, 2020
    Publication date: October 1, 2020
    Applicants: EDITAS MEDICINE, INC., THE BROAD INSTITUTE INC., THE UNIVERSITY OF IOWA RESEARCH FOUNDATION, MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng ZHANG, Deborah PALESTRANT, Beverly DAVIDSON, Jordi MATA-FINK, Edgardo RODRIGUEZ, Alexis BORISY
  • Patent number: 10781444
    Abstract: The present invention generally relates to libraries, compositions, methods, applications, kits and screens used in functional genomics that focus on gene function in a cell and that may use vector systems and other aspects related to Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas systems and components thereof. 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 utilizing the CRISPR-Cas system.
    Type: Grant
    Filed: December 17, 2015
    Date of Patent: September 22, 2020
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng Zhang, Ophir Shalem, Neville Espi Sanjana, John Doench, David Root, Ella Nicole Biewener Hartenian
  • Publication number: 20200291115
    Abstract: 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.
    Type: Application
    Filed: March 16, 2020
    Publication date: September 17, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventor: Feng Zhang
  • Publication number: 20200291382
    Abstract: The disclosure 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.
    Type: Application
    Filed: September 21, 2018
    Publication date: September 17, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Jonathan Gootenberg, David Benjamin Turitz Cox, Omar Abudayyeh, Soumya Kannan
  • Publication number: 20200283755
    Abstract: The invention provides for systems, methods, and compositions for targeting and editing nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a DNA-targeting Cpf1 protein, at least one guide molecule, and at least one adenosine deaminase protein or catalytic domain thereof.
    Type: Application
    Filed: May 18, 2018
    Publication date: September 10, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, David Benjamin Turitz Cox, Jonathan Gootenberg, Omar O. Abudayyeh, Bernd Zetsche, Jonathan Strecker
  • Publication number: 20200283743
    Abstract: In one aspect, embodiments disclosed herein are directed to engineered CRISPR-Cas effector proteins that comprise at least one modification compared to an unmodified CRISPR-Cas effector protein that enhances binding of the of the CRISPR complex to the binding site and/or alters editing preference as compared to wild type. In certain example embodiments, the CRISPR-Cas effector proteins a Type II effector protein. In certain other example embodiments, the Type V effector protein is Cas9 or an orthologs or engineered variant thereof. Example Cas9 proteins suitable for use in the embodiments disclosed herein are discussed in further detail below.
    Type: Application
    Filed: August 17, 2017
    Publication date: September 10, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng ZHANG, David Arthur SCOTT, Winston Xia YAN, Sourav CHOUDHURY, Matthias HEIDENREICH
  • Publication number: 20200277600
    Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect both 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.
    Type: Application
    Filed: September 7, 2018
    Publication date: September 3, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Jonathan Gootenberg, Omar Abudayyeh
  • Patent number: 10752628
    Abstract: The present invention includes compound and methods that are useful in treating certain cancers, such as synovial sarcomas.
    Type: Grant
    Filed: November 16, 2016
    Date of Patent: August 25, 2020
    Assignees: THE BROAD INSTITUTE, INC., PRESIDENT AND FELLOWS OF HARVARD COLLEGE, DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Cigall Kadoch, Enrique Garcia-Rivera, Micah Maetani, Stuart L. Schreiber
  • Publication number: 20200254443
    Abstract: Provided herein is a lateral flow diagnostic device and methods of using thereof. The device comprises a substrate and a first end, wherein the first end comprises a sample loading portion. The first end may further comprise a first region loaded with a detectable ligand, a CRISPR effector system, a detection construct, a first test band comprising a biotin ligand, and a second test band comprising a capture molecule for the detectable ligand. The detection construct may comprise an RNA oligonucleotide, having a first molecule such as FITC on a first end and a second molecule such as FAM on a second end. Contacting the sample loading portion with a sample causes the sample to flow from the sample loading portion of the substrate towards the first and second capture regions, thereby generating a detectable signal, which may be indicative of a disease state.
    Type: Application
    Filed: October 4, 2018
    Publication date: August 13, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Jonathan Gootenberg, Omar Abudayyeh
  • Publication number: 20200248229
    Abstract: Provided herein are methods of detecting a nucleic acid modification, methods for detecting off-target activity of a targeted nuclease specific for a selected target sequence, methods for determining cleavage efficiency of a targeted nuclease specific for a selected target sequence, methods for selecting a guide RNA from a plurality of guide RNAs specific for a selected target sequence, methods for enrichment of one or more nucleic acid molecules wherein a nucleic acid modification is made and kits of parts for use in such methods.
    Type: Application
    Filed: June 16, 2017
    Publication date: August 6, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Feng ZHANG, Winston Xia YAN, David Arthur SCOTT
  • Publication number: 20200248169
    Abstract: 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 cytidine deaminase protein or catalytic domain thereof.
    Type: Application
    Filed: June 26, 2018
    Publication date: August 6, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Jonathan Gootenberg, David Benjamin Turitz Cox, Omar Abudayyeh, Soumya Kannan
  • Patent number: 10711285
    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 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 prokaryotic and eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity.
    Type: Grant
    Filed: December 17, 2015
    Date of Patent: July 14, 2020
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Feng Zhang, Patrick Hsu, Chie-yu Lin, Fei Ran
  • Publication number: 20200202981
    Abstract: Embodiments disclosed herein provide methods, including computer-implemented methods, for designing guide sequence which may be incorporated into custom, large scale guide sequence libraries. The methods require only a list of target genes as input and utilize on target and off target scores to generate an optimal set of guide sequences for a set of target genes. In certain embodiments, the methods may also utilize multi-tissue RNA-sequencing data and/or protein annotation to design targets to genes that are highly expressed and/or contain a functional protein domain. The invention further comprises guide libraries, cells comprising said guide libraries. Computer-implemented embodiments further improve computer system function by reducing excessive user wait time through the use of data structures that reduce search from linear to logarithmic time.
    Type: Application
    Filed: July 6, 2018
    Publication date: June 25, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE, THE NEW YORK GENOME CENTER, NEW YORK UNIVERSITY
    Inventors: Neville Sanjana, Feng Zhang, Joshua A. Meier