Patents Assigned to President and Fellows of Harvard College
  • 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
  • Publication number: 20200197894
    Abstract: Microcapsules and techniques for the formation of microcapsules are generally described. In some embodiments, the microcapsules are formed in an emulsion (e.g., a multiple emulsion). In some embodiments, the microcapsule may be suspended in a carrying fluid containing the microcapsule that, in turn, contain the smaller droplets. In some embodiments, the microcapsules comprise a shell and a droplet at least partially contained within the shell (e.g., encapsulated within the shell), and may be suspended in a carrier fluid. In certain embodiments, the shell is a hydrogel comprising a poly(acid). In some cases, the poly(acid) is a polyanion. In some cases, the shell does not comprise a poly(base) or polycation (e.g., a polycationic poly electrolyte). In some embodiments, the microcapsules comprise a shell comprising a poly(acid) and a poly(anhydride).
    Type: Application
    Filed: August 20, 2018
    Publication date: June 25, 2020
    Applicant: President and Fellow of Harvard College
    Inventors: David A. Weitz, Joerg G. Werner, Sara Nawar, Brendon Deverney
  • Patent number: 10692391
    Abstract: In various embodiments, subject matter for improving discussions in connection with an educational resource is identified and summarized by analyzing annotations made by students assigned to a discussion group to identify high-quality annotations likely to generate responses and stimulate discussion threads, identifying clusters of high-quality annotations relating to the same portion or related portions of the educational resource, extracting and summarizing text from the annotations, and combining, in an electronically represented document, the extracted and summarized text and (i) at least some of the annotations and the portion or portions of the educational resource or (ii) clickable links thereto.
    Type: Grant
    Filed: August 27, 2019
    Date of Patent: June 23, 2020
    Assignee: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Gary King, Eric Mazur, Kelly Miller, Brian Lukoff
  • Patent number: 10687751
    Abstract: A computer system for generating a diagnostic tool by applying artificial intelligence to an instrument for diagnosis of a disorder, such as autism. For autism, the instrument can be a caregiver-directed set of questions designed for an autism classification tool or an observation of the subject in a video, video conference, or in person and associated set of questions about behavior that are designed for use in a separate autism classification tool. The computer system can have one or more processors and memory to store one or more computer programs having instructions for generating a highly statistically accurate set of diagnostic items selected from the instrument, which are tested against a first test using a technique using artificial intelligence and a second test against an independent source. Also, a computer implemented method and a non-transitory computer-readable storage medium are disclosed.
    Type: Grant
    Filed: August 3, 2016
    Date of Patent: June 23, 2020
    Assignee: President And Fellows of Harvard College
    Inventor: Dennis Wall
  • Patent number: 10689044
    Abstract: A pneumatically powered, fully untethered mobile soft robot is described. Composites consisting of silicone elastomer, polyaramid fabric, and hollow glass microspheres were used to fabricate a sufficiently large soft robot to carry the miniature air compressors, battery, valves, and controller needed for autonomous operation. Fabrication techniques were developed to mold a 0.65 meter long soft body with modified Pneumatic network actuators capable of operating at the elevated pressures (up to 138 kPa) required to actuate the legs of the robot and hold payloads of up to 8 kg. The soft robot is safe to handle, and its silicone body is innately resilient to a variety of adverse environmental conditions including snow, puddles of water, direct (albeit limited) exposure to flames, and the crushing force of being run over by an automobile.
    Type: Grant
    Filed: June 30, 2015
    Date of Patent: June 23, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: Michael T. Tolley, Robert F. Shepherd, Bobak Mosadegh, Robert J. Wood, George M. Whitesides
  • Publication number: 20200190493
    Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins comprise a Gam protein, a napDNAbp, and a cytidine deaminase. In some embodiments, the fusion proteins further comprise a UGI domain. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of a Gam protein, a cytidine deaminase and nucleic acid editing proteins or domains, are provided.
    Type: Application
    Filed: August 30, 2018
    Publication date: June 18, 2020
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, Kevin Tianmeng Zhao, Yongjoo Kim
  • Patent number: 10683524
    Abstract: The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer.
    Type: Grant
    Filed: August 7, 2017
    Date of Patent: June 16, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: David A. Weitz, Jeremy Agresti, Liang-Yin Chu, Jin-Woong Kim, Amy Rowat, Morten Sommer, Gautam Dantas, George Church
  • Patent number: 10682410
    Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases.
    Type: Grant
    Filed: September 5, 2014
    Date of Patent: June 16, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: David R. Liu, John Anthony Zuris, David B. Thompson
  • Patent number: 10683490
    Abstract: Methods of making mutant Cas9 proteins are described.
    Type: Grant
    Filed: June 13, 2019
    Date of Patent: June 16, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: Alejandro Chavez, Frank J. Poelwijk, George M. Church
  • Patent number: 10682400
    Abstract: The present invention comprises compositions, methods, and devices for enhancing an endogenous immune response against a cancer. Devices and methods provide therapeutic immunity to subjects against cancer.
    Type: Grant
    Filed: April 30, 2015
    Date of Patent: June 16, 2020
    Assignees: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.
    Inventors: Omar Abdel-Rahman Ali, David J. Mooney, Glenn Dranoff
  • Patent number: 10683552
    Abstract: The present invention relates to clonal expansion of somatic cells in subjects, and acquired selective advantage of cell clones during the lifetime of a subject. In particular, the invention relates to methods for predicting the development of cancer based on the observation of specific genetic mutations in somatic cell clones, as well as to methods for treating or preventing cancer in a subject, in which clonal expansion of cells comprising specific modifications is observed.
    Type: Grant
    Filed: November 23, 2015
    Date of Patent: June 16, 2020
    Assignees: Presidents and Fellows of Harvard College, The Broad Institute, Inc.
    Inventors: Steven Andrew McCarroll, Giulio Genovese
  • Publication number: 20200183050
    Abstract: A multi-layered lens comprises a plurality of metasurface layers. At least some layers of the plurality of metasurface layers include features that exhibit angular phase controls. The angular phases of the at least some layers cause an angular aberration correction or an angle convergence that focuses light onto a focal point regardless of angles of incidence.
    Type: Application
    Filed: June 19, 2018
    Publication date: June 11, 2020
    Applicants: PRESIDENT AND FELLOWS OF HARVARD COLLEGE, PRINCETON UNIVERSITY
    Inventors: Zin LIN, Federico CAPASSO, Alejandro W. RODRIGUEZ, Marko LONCAR, Benedikt GROEVER
  • Publication number: 20200179050
    Abstract: An insertable catheter device includes a shaft including a proximal end and a distal end, an expandable balloon, and an actuator configured to expand and retract the expandable balloon. The actuator includes a fluid conduit that extends through the shaft and is coupled with the expandable balloon to enable inflation and retraction of the expandable balloon via injection or withdrawal of a fluid to or from the expandable balloon via the fluid conduit. The expandable balloon is displaceably retractable into the shaft and extendable from the shaft. A fluid pump is coupled with the fluid conduit to pump the fluid through the fluid conduit. A patch is positioned to be displaced by the expandable balloon when the expandable balloon is inflated, and the expandable balloon is displaceably retractable into the shaft and displaceably extendable from the shaft.
    Type: Application
    Filed: February 4, 2020
    Publication date: June 11, 2020
    Applicants: President and Fellows of Harvard College, The Brigham and Women's Hospital, Children's Medical Center Corporation, Massachusetts Institute of Technology
    Inventors: Conor J. Walsh, Ellen T. Roche, Panagiotis Polygerinos, Lucia R. Schuster, Jeffrey Michael Karp, Yuhan Lee, Pedro J. del Nido, Assunta Fabozzo, Ingeborg Friehs, Steven Charles Wasserman
  • Publication number: 20200181720
    Abstract: Provided herein is a nucleic acid detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind to corresponding target molecules; an RNA-based masking construct; and optionally, nucleic acid amplification reagents to amplify target RNA molecules in a sample. In another aspect, the embodiments provide a polypeptide detection system comprising: a CRISPR system comprising an effector protein and one or more guide RNAs designed to bind a trigger RNA, an RNA-based masking construct; and one or more detection aptamers comprising a masked RNA polymerase promoter binding site or a masked primer binding site. In some embodiments, the system may be used to detect viruses in samples.
    Type: Application
    Filed: March 15, 2018
    Publication date: June 11, 2020
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Omar ABUDAYYEH, James Joseph COLLINS, Jonathan GOOTENBERG, Feng ZHANG, Eric S. LANDER, Pardis SABETI, Catherine Amanda FREIJE, Cameron MYHRVOLD
  • Publication number: 20200179374
    Abstract: The present invention features a method of reducing tactile dysfunction or anxiety in a subject diagnosed with Autism Spectrum Disorder, Rett Syndrome, or Fragile X syndrome by administering a GABAA agent having reduced blood brain barrier or by expressing a nucleic acid encoding an exogenous alpha or beta subunit of a GABAA receptor in dorsal root ganglion neurons in the subject using a vector.
    Type: Application
    Filed: June 8, 2017
    Publication date: June 11, 2020
    Applicant: President and Fellows of Harvard College
    Inventors: Lauren L. Orefice, David D. Ginty
  • Publication number: 20200181619
    Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable proteins, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and, in certain instances, cleavage activity of RNA-programmable proteins (e.g., RNA-programmable endonucleases). By incorporating ligand-responsive self-cleaving catalytic RNAs (aptazymes) into guide RNAs, a set of aptazyme-embedded guide RNAs was developed that enable small molecule-controlled nuclease-mediated genome editing and small molecule-controlled base editing, as well as small molecule-dependent transcriptional activation in mammalian cells.
    Type: Application
    Filed: May 11, 2018
    Publication date: June 11, 2020
    Applicant: President and Fellows of Harvard College
    Inventors: Weixin Tang, Johnny Hao Hu, David R. Liu
  • Patent number: 10675626
    Abstract: Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply.
    Type: Grant
    Filed: September 17, 2019
    Date of Patent: June 9, 2020
    Assignees: President and Fellows of Harvard College, Brandeis University
    Inventors: Seth Fraden, Hakim Boukellal, Yanwei Jia, Seila Selimovic, Amy Rowat, Jeremy Agresti, David A. Weitz
  • Publication number: 20200172896
    Abstract: The present invention provides methods and compositions for performing ordered multi-step syntheses involving modified nucleic acids by nucleic acid-mediated chemistry. This approach is useful for generating sequence-defined highly functionalized nucleic acid polymers. The invention also provides modified nucleic acid polymers that bind to proteins of interest (e.g., PCSK9 and IL-6), which are implicated in human disease.
    Type: Application
    Filed: July 6, 2018
    Publication date: June 4, 2020
    Applicant: President and Fellows of Harvard College
    Inventors: David R. Liu, Zhen Chen, Phillip Andrew Lichtor
  • Publication number: 20200172845
    Abstract: Described herein are methods inducing the uptake of an agent by a cell. Aspects of the invention relate to physically compressing the cell to induce perturbations (e.g., holes) in the cell membrane or wall. An agent is taken up by the cell through induced perturbations.
    Type: Application
    Filed: July 18, 2018
    Publication date: June 4, 2020
    Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Charles James BAKER, Ghee Chuan LAI, Dirk LANDGRAF, Burak OKUMUS, Johan PAULSSON
  • Publication number: 20200174007
    Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.
    Type: Application
    Filed: November 22, 2019
    Publication date: June 4, 2020
    Applicants: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.
    Inventors: Craig Braun, Wilhelm Haas, Steven P. Gygi, Gregory H. Bird, Loren D. Walensky, Martin Helmut Wuhr, Brian K. Erickson