Patents by Inventor George M. Church

George M. Church 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).

  • Enzymatic Nucleic Acid Synthesis
    Publication number: 20190145013
    Abstract: The present disclosure provides methods of activating an enzyme, such as error prone or template independent polymerase, using electricity to alter pH of a reaction zone and reaction site from an inactivating pH at which the enzyme is inactive to an activating pH at which the enzyme is active to add a nucleotide to an initiator or growing polymer chain. The activating pH can then be changed back to an inactivating pH and the process repeated as many times as desired to produce a target nucleic acid sequence.
    Type: Application
    Filed: May 9, 2017
    Publication date: May 16, 2019
    Inventors: Reza Kalhor, Henry Hung-yi Lee, George M. Church
  • Methods for retrievable information storage using nucleic acids
    Patent number: 10289801
    Abstract: A method of storing information using monomers such as nucleotides is provided including converting a format of information into a plurality of bit sequences of a bit stream with each having a corresponding bit barcode, converting the plurality of bit sequences to a plurality of corresponding oligonucleotide sequences using one bit per base encoding, synthesizing the plurality of corresponding oligonucleotide sequences on a substrate having a plurality of reaction locations, and storing the synthesized plurality of corresponding oligonucleotide sequences.
    Type: Grant
    Filed: August 4, 2017
    Date of Patent: May 14, 2019
    Assignee: President and Fellows of Harvard College
    Inventor: George M. Church
  • Method and System of Nanopore-based Information Encoding
    Publication number: 20190136309
    Abstract: This invention provides methods and systems of DNA synthesis including providing an encoding unit comprising an enzyme, a single-stranded DNA (ssDNA) and a nanopore, providing a lipid bilayer having on opposite sides a cis and a trans reservoir each having a different buffer composition, wherein the nanopore is within the lipid bilayer and the enzyme and the ssDNA are in the cis reservoir, providing an electrode over the lipid bilayer wherein the electrode can modulate voltage across the lipid bilayer, wherein the enzyme catalyzes DNA synthesis in response to the voltage.
    Type: Application
    Filed: April 19, 2017
    Publication date: May 9, 2019
    Applicant: President and Fellows of Harvard College
    Inventors: George M. Church, Mirkó Palla, Peter Benjamin Stranges, Jeffrey Matthew Nivala
  • Methods for Increasing Efficiency of Nuclease-Mediated Gene Editing in Stem Cells
    Publication number: 20190127762
    Abstract: Inhibiting p53 or Bax can be used to improve nuclease-mediated gene targeting frequencies in stem cells. This inhibition can be achieved, e.g., by overexpression of anti-apoptosis proteins or by silencing or reducing p53 or Bax expression. This technique can be used in conjunction with other rapidly developing CRISPR technologies, including improvements in specificity, other types of nucleases, and further enrichment, screening, and selection schemes, to expand the use of stem cells in experimental studies and tissue engineering for therapeutic purposes.
    Type: Application
    Filed: April 19, 2017
    Publication date: May 2, 2019
    Inventors: George M. Church, Susan M. Byrne
  • RNA-guided human genome engineering
    Patent number: 10273501
    Abstract: A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.
    Type: Grant
    Filed: July 2, 2015
    Date of Patent: April 30, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: George M. Church, Prashant G. Mali, Luhan Yang
  • Methods for Retrievable Information Storage Using Nucleic Acids
    Publication number: 20190121936
    Abstract: A method of storing information using monomers such as nucleotides is provided including converting a format of information into a plurality of bit sequences of a bit stream with each having a corresponding bit barcode, converting the plurality of bit sequences to a plurality of corresponding oligonucleotide sequences using one bit per base encoding, synthesizing the plurality of corresponding oligonucleotide sequences on a substrate having a plurality of reaction locations, and storing the synthesized plurality of corresponding oligonucleotide sequences.
    Type: Application
    Filed: December 12, 2018
    Publication date: April 25, 2019
    Inventor: George M. Church
  • Method and apparatus for volumetric imaging of a three-dimensional nucleic acid containing matrix
    Patent number: 10266888
    Abstract: Methods of volumetric imaging of a three-dimensional matrix of nucleic acids within a cell is provided. An automated apparatus for sequencing and volumetric imaging of a three-dimensional matrix of nucleic acids is provided.
    Type: Grant
    Filed: May 2, 2018
    Date of Patent: April 23, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Evan R. Daugharthy, Richard C. Terry, Je-Hyuk Lee, George M. Church, Benjamin W. Pruitt
  • Methods and Compositions for the Single Tube Preparation of Sequencing Libraries Using Cas9
    Publication number: 20190112599
    Abstract: Methods and compositions of single tube preparation of sequencing libraries from a target DNA are provided. The methods include contacting the DNA with a composition comprising Cas9 endonuclease, a first and a second guide RNAs, a ligase, and sequencing adapters, subjecting the composition to thermal cycling to cleave the DNA at the sites flanking the regions of interest by the RNA guided endonuclease, and subjecting the composition to a temperature to allow ligation of the cleaved DNA fragments including the regions of interest with the sequencing adapters to generate the sequencing libraries.
    Type: Application
    Filed: March 29, 2017
    Publication date: April 18, 2019
    Inventors: George M. Church, Benjamin W. Pruitt, Richard C. Terry
  • Methods and Systems of Cell-Free Enzyme Discovery and Optimization
    Publication number: 20190112598
    Abstract: Methods and systems of cell-fee enzyme discovery and optimization are provided.
    Type: Application
    Filed: March 7, 2017
    Publication date: April 18, 2019
    Inventors: George M. CHURCH, Jameson K. ROGERS, Marc GUELL, Alexander GARRUSS
  • Enzymatic Nucleic Acid Synthesis
    Publication number: 20190112626
    Abstract: The disclosure provides methods for making a polynucleotide wherein the addition of nucleotides can be physically, chemically and/or enzymatically controlled. The methods include combining a selected nucleotide, cations, an error prone or template independent DNA polymerase at a reaction site including an initiator sequence attached thereto and having a 3? terminal nucleotide, wherein the reaction reagents can be modulated and under conditions that allow covalent addition of one or more of a selected nucleotide to the 3? terminal nucleotide such that the selected nucleotide becomes a 3? terminal nucleotide, and repeating the addition step until the polynucleotide is formed.
    Type: Application
    Filed: March 30, 2017
    Publication date: April 18, 2019
    Inventors: Henry Hung-yi Lee, George M. Church, Reza Kalhor
  • High-throughput single cell barcoding
    Patent number: 10246703
    Abstract: Methods and compositions for high-throughput, single cell analyzes are provided. The methods and compositions can be used for analysis of genomes and transcriptomes, as well as antibody discovery, HLA typing, haplotyping and drug discovery.
    Type: Grant
    Filed: January 18, 2018
    Date of Patent: April 2, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: George M. Church, Francois Vigneault
  • Methods for High-Throughput Labelling and Detection of Biological Features In Situ Using Microscopy
    Publication number: 20190085383
    Abstract: Methods of labelling one or more subcellular components (e.g., an organelle and/or subcellular region) in vivo are provided. Methods of labelling a protein in vivo are provided. Methods of determining a nucleic acid sequence in situ are also provided.
    Type: Application
    Filed: November 27, 2018
    Publication date: March 21, 2019
    Inventors: George M. Church, Je-Hyuk Lee, Evan R. Daugharthy
  • Compositions and methods for analyte detection
    Patent number: 10227639
    Abstract: The inventions provided herein relate to detection reagents, compositions, methods, and kits comprising the detection reagents for use in detection, identification, and/or quantification of analytes in a sample. Such detection reagents and methods described herein allow multiplexing of many more labeled species in the same procedure than conventional methods, in which multiplexing is limited by the number of available and practically usable colors.
    Type: Grant
    Filed: December 21, 2012
    Date of Patent: March 12, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Daniel Levner, Je-Hyuk Lee, George M. Church, Michael Super
  • Method of Making Polynucleotides Using Closed-Loop Verification
    Publication number: 20190062804
    Abstract: A method for making a polynucleotide is provided including (a) delivering one or more reaction reagents including an error prone or template independent DNA polymerase, cations and a selected nucleotide to a reaction site including an initiator sequence having a terminal nucleotide for a time period and under conditions capable of covalently adding one or more of the selected nucleotide to the terminal nucleotide at the 3? end of the initiator such that the selected nucleotide becomes a terminal nucleotide, and (b) determining whether the selected nucleotide has been added to the terminal nucleotide, wherein if the selected nucleotide has not been added to the terminal nucleotide, then repeating step (a) until the selected nucleotide has been added, and (c) repeating steps (a) and (b) until the polynucleotide is formed.
    Type: Application
    Filed: March 9, 2017
    Publication date: February 28, 2019
    Inventors: George M. Church, Kettner John Frederick Griswold, Jr.
  • Mitochondrial Genome Editing and Regulation
    Publication number: 20190062739
    Abstract: Methods and compositions of altering mitochondrial DNA of a eukaryotic cell are provided using one or more of a mitochondrial specific adeno-associated virus to deliver one or more nucleic acids encoding CRISPR system including a Cas9 protein or its nuclease inactive variant and a guide RNA into a mitochondria for expression within the mitochondria. The Cas9 system can cut, nick or regulate a target mitochondrial nucleic acid.
    Type: Application
    Filed: February 2, 2017
    Publication date: February 28, 2019
    Applicant: President and Fellows of Harvard College
    Inventors: George M. Church, Luhan Yang, Margo R. Monroe
  • Assembly of nucleic acid sequences in emulsions
    Patent number: 10202628
    Abstract: Methods and compositions for synthesizing nucleic acid sequences in an emulsion are provided.
    Type: Grant
    Filed: February 14, 2013
    Date of Patent: February 12, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: George M. Church, Richard C. Terry, Sriram Kosuri, Di Zhang
  • Mutant Cas9 Proteins
    Publication number: 20190040371
    Abstract: Methods of making mutant Cas9 proteins are described.
    Type: Application
    Filed: October 11, 2018
    Publication date: February 7, 2019
    Inventors: Alejandro Chavez, Frank J. Poelwijk, George M. Church
  • Methods for Detecting and Identifying Genomic Nucleic Acids
    Publication number: 20190032121
    Abstract: The present invention relates to a method of identifying a target genomic nucleic acid sequence including hybridizing a set of probes to the target genomic nucleic acid sequence, wherein the set of probes has a unique associated barcode sequence for identification of the target genomic nucleic acid sequence, wherein each probe of the set includes (1) a complementary sequence complementary to a first strand of the target genomic nucleic acid sequence and (2) the associated barcode sequence or a portion of the associated barcode sequence, sequencing the associated barcode sequence from probes hybridized to the target genomic nucleic acid sequence using a fluorescence-based sequencing method, and identifying the target genomic nucleic acid sequence by the sequenced barcode sequence.
    Type: Application
    Filed: March 17, 2017
    Publication date: January 31, 2019
    Inventors: Evan R. Daugharthy, Sonny C. Nguyen, Chao-ting Wu, George M. Church
  • Method for Generating A Three-Dimensional Nucleic Acid Containing Matrix
    Publication number: 20190024144
    Abstract: Methods of making a three-dimensional matrix of nucleic acids within a cell is provided.
    Type: Application
    Filed: October 11, 2018
    Publication date: January 24, 2019
    Inventors: George M. Church, Je-Hyuk Lee, Richard C. Terry, Evan R. Daugharthy
  • Methods for high-throughput labelling and detection of biological features in situ using microscopy
    Patent number: 10179932
    Abstract: Methods of labelling one or more subcellular components (e.g., an organelle and/or subcellular region) in vivo are provided. Methods of labelling a protein in vivo are provided. Methods of determining a nucleic acid sequence in situ are also provided.
    Type: Grant
    Filed: July 10, 2015
    Date of Patent: January 15, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: George M. Church, Je-Hyuk Lee, Evan R. Daugharthy