Patents by Inventor Paul Blainey

Paul Blainey 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).

  • Publication number: 20210395709
    Abstract: The disclosure provides Cas9 protein variants that are thermostable at elevated temperatures (e.g., at least 70° C. or above). A Cas9 protein may have at least 75% sequence identity to a wild-type Cas9 protein (e.g., a wild-type Cas9 protein having the sequence of SEQ ID NO:1) and/or one or more amino acid substitutions relative to the wild-type Cas9 protein.
    Type: Application
    Filed: October 17, 2019
    Publication date: December 23, 2021
    Inventors: Stephen R. Quake, Stephanie Tzouanas Schmidt, Feiqiao Brian Yu, Paul Blainey, Andrew Paul May
  • Publication number: 20210340527
    Abstract: Embodiments disclosed herein are directed to a new genetic perturbation and screening method that combines advantages of pooled perturbation with imaging assays for complex phenotypes. Specifically, the method may be used to screen pooled genomic perturbations to identify phenotypes and to identify perturbed genes at the single-cell level using optical barcodes. A major advantage offered by this approach is the ability to screen for any cellular phenotype that can be identified by high-resolution microscopy—including live-cell phenotypes, protein localization, or highly multiplexed expression profile and mRNA localization by RNA-FISH—in conjunction with a large array of genetic perturbations applied as a pool in a single test volume.
    Type: Application
    Filed: May 14, 2021
    Publication date: November 4, 2021
    Inventors: Paul Blainey, David Feldman
  • Publication number: 20210300974
    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: Application
    Filed: October 13, 2020
    Publication date: September 30, 2021
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Paul Blainey, Anthony Kulesa, Kan Xiong
  • Patent number: 11046952
    Abstract: Embodiments disclosed herein are directed to a new genetic perturbation and screening method that combines advantages of pooled perturbation with imaging assays for complex phenotypes. Specifically, the method may be used to screen pooled genomic perturbations to identify phenotypes and to identify perturbed genes at the single-cell level using optical barcodes. A major advantage offered by this approach is the ability to screen for any cellular phenotype that can be identified by high-resolution microscopy—including live-cell phenotypes, protein localization, or highly multiplexed expression profile and mRNA localization by RNA-FISH—in conjunction with a large array of genetic perturbations applied as a pool in a single test volume.
    Type: Grant
    Filed: March 16, 2016
    Date of Patent: June 29, 2021
    Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Paul Blainey, David Feldman
  • Publication number: 20210180058
    Abstract: The subject matter disclosed herein is generally directed to methods and compositions for tagging cells of interest, tracking evolution of the tagged cells, and recovering the original tagged cells for further study. Specifically, cells are tagged with a DNA construct encoding a barcode sequence comprising a guide sequence. Barcoded cells can then be recovered using a reporter construct having CRISPR target sequences specific for the cell having a barcode of interest.
    Type: Application
    Filed: October 31, 2018
    Publication date: June 17, 2021
    Inventors: Pratiti BANDOPADHAYAY, Rameen BEROUKHIM, Paul BLAINEY, David FELDMAN, Cory JOHANNESSEN, Funien TSAI
  • Publication number: 20210139941
    Abstract: Provided herein are methods for screening biological functions of microscale biological systems comprises segregating each microscale biological system from a set of microscale biological systems to be screened into individual discrete volumes, the individual discrete volume comprising a first polymer. The first polymer is then forced or allowed to polymerize to form a set of polymerized beads that encapsulate an individual microscale biological system. The polymerized beads are further encapsulated in a second droplet comprising a second polymer and one or more reporter elements. The reporter elements are configured to produce a readout upon detecting the absence or presence of a biological function to be screened. The second polymer is then forced or allowed to polymerize to form an outer capsule around each individual bead thereby forming a set of encapsulated beads. One or more biological functions of the double-encapsulated system are identified by detecting the readout of the reporters.
    Type: Application
    Filed: April 13, 2018
    Publication date: May 13, 2021
    Inventors: Paul Blainey, Navpreet Ranu
  • Publication number: 20210138468
    Abstract: Embodiments disclosed herein are directed to microfluidic devices that allow for scalable on-chip screening of combinatorial libraries and methods of use thereof. Droplets comprising individual molecular species to be screened are loaded onto the microfluidic device. The droplets are labeled by methods known in the art, including but not limited to barcoding, such that the molecular species in each droplet can be uniquely identified. The device randomly sorts the droplets into individual microwells of an array of microwells designed to hold a certain number of individual droplets in order to derive combinations of the various molecular species. The paired droplets are then merged in parallel to form merged droplets in each microwell, thereby avoiding issues associated with single stream merging. Each microwell is then scanned, e.g., using microscopy, such as high content imaging microscopy, to detect the optical labels, thereby identifying the combination of molecular species in each microwell.
    Type: Application
    Filed: December 28, 2020
    Publication date: May 13, 2021
    Inventors: Paul Blainey, Anthony Kulsea, Jared Kehe
  • Patent number: 10982289
    Abstract: The present invention relates to novel hybridization probes useful for rapid hybridization to realize a practicable and affordable pathogen diagnostic based on RNA signature detection, technology and hardware. In particular, the present invention relates to a nucleic acid structure which may comprise nucleic acid tiles, wherein each nucleic acid tile comprises nucleic acid oligomers, wherein each nucleic acid oligomer hybridizes to each other thereby forming a nucleic acid tile.
    Type: Grant
    Filed: September 9, 2015
    Date of Patent: April 20, 2021
    Assignees: The Broad Institute Inc., Massachusetts Institute of Technology
    Inventors: Paul Blainey, Jacob de Riba Borrajo
  • Patent number: 10981167
    Abstract: Embodiments disclosed herein are directed to microfluidic devices that allow for scalable on-chip screening of combinatorial libraries and methods of use thereof. Droplets comprising individual molecular species to be screened are loaded onto the microfluidic device. The droplets are labeled by methods known in the art, including but not limited to barcoding, such that the molecular species in each droplet can be uniquely identified. The device randomly sorts the droplets into individual microwells of an array of microwells designed to hold a certain number of individual droplets in order to derive combinations of the various molecular species. The paired droplets are then merged in parallel to form merged droplets in each microwell, thereby avoiding issues associated with single stream merging. Each microwell is then scanned, e.g., using microscopy, such as high content imaging microscopy, to detect the optical labels, thereby identifying the combination of molecular species in each microwell.
    Type: Grant
    Filed: March 18, 2016
    Date of Patent: April 20, 2021
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Paul Blainey, Anthony Kulesa, Jared Kehe
  • Patent number: 10962527
    Abstract: A system and method for isolating target substrates includes a microfluidic chip, comprising a plurality of processing units, each processing unit comprising: an inlet port, a plurality of first chambers connected to the inlet port by a fluid channel, the fluid channel comprising a plurality of valves, a plurality of second chambers, each of the second chambers connected to a respective first chamber by a fluid channel, each fluid channel including a controllable blocking valve, and a plurality of respective outlet ports, each outlet port in fluid communication with a respective one of said second chambers and each outlet port including a blocking valve. A magnet is adjacent the microfluidic chip and is movable relative to the microfluidic chip. A valve control is capable of actuating certain ones of the controllable blocking valves in response to a control signal.
    Type: Grant
    Filed: February 3, 2017
    Date of Patent: March 30, 2021
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, THE GENERAL HOSPITALL CORPORATION
    Inventors: Paul Blainey, Dwayne Vickers, Nir Hacohen
  • Publication number: 20210071240
    Abstract: The present disclosure relates to compositions and methods for detection of single-stranded breaks (SSBs) in dsDNA, including in genomic DNA. Measurement of the precise location of SSB damage in DNA, e.g.
    Type: Application
    Filed: April 18, 2019
    Publication date: March 11, 2021
    Applicants: MASSACHUSETTS INSTITUTE OF TECHNOLOGY, THE BROAD INSTITUTE, INC.
    Inventors: Sarah DiIorio, Joshua Elacqua, Arnaud Gutierrez, Navpreet Ranu, Paul Blainey
  • Publication number: 20200392479
    Abstract: The present invention relates to the analysis of complex single cell sequencing libraries. Disclosed are methods for enrichment of library members based on the presence of cell-of origin barcodes to identify and concentrate DNA that is relevant to interesting cells or components that would be expensive or difficult to study otherwise. Also, disclosed are methods of capturing cDNA library molecules by use of CRISPR systems, hybridization or PCR. The present invention allows for identifying the properties of rare cells in single cell RNA-seq data and accurately profile them through clustering approaches. Further information on transcript abundances from subpopulations of single cells can be analyzed at a lower sequencing effort. The methods also allow for linking TCR alpha and beta chains at the single cell level.
    Type: Application
    Filed: October 23, 2018
    Publication date: December 17, 2020
    Inventors: Paul Blainey, Navpreet Ranu, Todd Gierahn, Chris Love
  • Publication number: 20200353033
    Abstract: The present disclosure relates compositions and methods for combinatorial drug discovery in nanoliter droplets. More particularly, the disclosure relates to novel synergistic agents that increase efficacy of antibiotic agents to treat bacterial infection.
    Type: Application
    Filed: October 9, 2018
    Publication date: November 12, 2020
    Applicants: The Broad Institute, Inc., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Paul Blainey, Anthony Kulesa, Jared Kehe
  • 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
  • Publication number: 20200232009
    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 culture 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: Application
    Filed: August 25, 2016
    Publication date: July 23, 2020
    Inventors: David Feldman, Daniel Sazer, Paul Blainey
  • Publication number: 20200199660
    Abstract: Most somatic mutations are harmless, but some lead to a phenotypic consequence. The present invention provides methods and tools to elucidate exactly how mutations appear in the genome using detection of mutations in a cell lineage. The present invention also provides for determining the effect of environmental stimuli and drugs on somatic mutations. Finally, the present invention provides for personalized medicine by determining the effect of drugs on somatic mutations in cells obtained from a subject in need thereof.
    Type: Application
    Filed: May 10, 2018
    Publication date: June 25, 2020
    Inventors: Soohong Kim, Paul Blainey, Yehuda Brody, Robert Kimmerling
  • Publication number: 20200078296
    Abstract: It has been discovered that lung tumor growth is associated with a dysregulation of the local microbiota, including an increased total bacterial load and reduced bacterial diversity in the airway. In the lungs, commensal bacteria, which are otherwise non-pathogenic and colonize pulmonary tissue at a much lower density in healthy individuals, provoke chronic inflammation and exacerbation of lung cancer through tumor-infiltrating immune cells. Thus, targeting the lung microbiota and its responding immune pathways is useful in treating lung cancer. Disclosed are compositions and methods targeting the lung microbiota and its responding immune pathways in a subject by specific targeting of commensal bacteria in the subject. Typically, the methods involve administering an effective amount of one or more therapeutics such as an antibiotic that reduces the local bacterial load, blocks or depletes tumor-infiltrating immune cells, and/or locally inhibits one or more cytokines or chemokines.
    Type: Application
    Filed: June 21, 2019
    Publication date: March 12, 2020
    Inventors: Chengcheng Jin, Georgia Lagoudas, Paul Blainey, Tyler Jacks
  • Publication number: 20200063198
    Abstract: The present invention provides improved methods for detecting contamination in WGA reagents as well as improved methods for quantitating nucleic acids, such as DNA. The present invention relates to novel methods of quantifying nucleic acids involving whole-genome amplification (WGA) reaction components and a dye molecule to detects nucleic acids and partitioning reactions to quantify nucleic acids.
    Type: Application
    Filed: November 4, 2019
    Publication date: February 27, 2020
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology
    Inventors: Paul Blainey, Liyi Xu
  • Publication number: 20200017861
    Abstract: The present invention provides for methods to obtain multiple information-rich samples at different time points from the same cell while minimally disrupting the cell. The subject matter disclosed herein is generally related to nucleic acid constructs for continuous monitoring of live cells. Specifically, the subject matter disclosed herein is directed to nucleic acid constructs that encode a fusion protein and a construct RNA sequence that induce live cells to self-report cellular contents while maintaining cell viability. The present invention may be used to monitor gene expression in single cells while maintaining cell viability.
    Type: Application
    Filed: September 21, 2017
    Publication date: January 16, 2020
    Inventors: Paul BLAINEY, Jacob BORRAJO, Mohamad NAJIA, Atray DIXIT
  • Patent number: 10487354
    Abstract: The present invention relates to methods of quantifying nucleic acids involving (a) contacting a sample to be tested with whole-genome amplification (WGA) reaction components and a dye molecule to form a reaction sample, wherein the dye molecule detects the nucleic acid; (b) partitioning the reaction sample wherein each partitioned reaction sample corresponds to a single reaction; (c) allowing the reaction to occur in the partitioned reaction sample and (d) determining the number of partitioned reaction samples having the dye molecule, wherein the dye molecule indicates the presence of the nucleic acid; thereby quantifying the nucleic acid in the sample to be tested.
    Type: Grant
    Filed: September 11, 2015
    Date of Patent: November 26, 2019
    Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Paul Blainey, Liyi Xu