Patents Assigned to President and Fellows of Harvard College
  • Publication number: 20190218602
    Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA. Methods for making and using and uses of such systems, methods, and compositions and products from such methods and uses are also disclosed and claimed.
    Type: Application
    Filed: July 27, 2018
    Publication date: July 18, 2019
    Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College
    Inventors: Feng ZHANG, Bernd ZETSCHE, Jonathan S. GOOTENBERG, Omar O. ABUDAYYEH, Ian SLAYMAKER
  • Publication number: 20190218276
    Abstract: Transcriptomes of individual neurons provide rich information about cell types and dynamic states. However, it is difficult to capture rare dynamic processes, such as adult neurogenesis, because isolation from dense adult tissue is challenging, and markers for each phase are limited. Here, Applicants developed Nuc-seq, Div-Seq, and Dronc-Seq. Div-seq combines Nuc-Seq, a scalable single nucleus RNA-Seq method, with EdU-mediated labeling of proliferating cells. Nuc-Seq can sensitively identify closely related cell types within the adult hippocampus. Div-Seq can track transcriptional dynamics of newborn neurons in an adult neurogenic region in the hippocampus. Dronc-Seq uses a microfluidic device to co-encapsulate individual nuclei in reverse emulsion aqueous droplets in an oil medium together with one uniquely barcoded mRNA-capture bead. Finally, Applicants found rare adult newborn GABAergic neurons in the spinal cord, a non-canonical neurogenic region.
    Type: Application
    Filed: October 27, 2016
    Publication date: July 18, 2019
    Applicants: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Aviv Regev, Feng Zhang, Naomi Habib, Yinqing Li, Matthias Heidenreich, Lukasz Swiech, Anindita Basu, David Weitz, Inbal Avraham Davidi
  • Patent number: 10355229
    Abstract: The present invention generally relates to nanoscale wires and tissue engineering. Systems and methods are provided in various embodiments for preparing cell scaffolds that can be used for growing cells or tissues, where the cell scaffolds comprise nanoscale wires. In some cases, the nanoscale wires can be connected to electronic circuits extending externally of the cell scaffold. Such cell scaffolds can be used to grow cells or tissues which can be determined and/or controlled at very high resolutions, due to the presence of the nanoscale wires, and such cell scaffolds will find use in a wide variety of novel applications, including applications in tissue engineering, prosthetics, pacemakers, implants, or the like. This approach thus allows for the creation of fundamentally new types of functionalized cells and tissues, due to the high degree of electronic control offered by the nanoscale wires and electronic circuits.
    Type: Grant
    Filed: July 8, 2016
    Date of Patent: July 16, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Charles M. Lieber, Bozhi Tian, Jia Liu
  • Patent number: 10352945
    Abstract: The invention provides methods, cells and constructs for optical measurement of membrane potential. These methods can be used in cells that are not accessible to presently available methods using electrodes. The methods can be directed to, for example, high-throughput drug screening assays to determine agents that can affect membrane potential of a target cell.
    Type: Grant
    Filed: October 13, 2017
    Date of Patent: July 16, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Adam Ezra Cohen, Joel Kralj, Adam D. Douglass
  • Patent number: 10350191
    Abstract: The specification provides compositions and methods to treat neurodegenerative diseases.
    Type: Grant
    Filed: December 17, 2018
    Date of Patent: July 16, 2019
    Assignees: Children's Medical Center Corporation, The General Hospital Corporation, President and Fellows of Harvard College
    Inventors: Clifford J. Woolf, Brian J. Wainger, Evangelos Kiskinis, Kevin Eggan
  • Patent number: 10349927
    Abstract: A soft material retractor includes at least two soft actuators, each actuator having at least one pressurizable interior space, wherein the actuator has a first flexible resting state and a second stiffer pressurized state; and a flexible sheet spanning the actuators such that the actuators can be spaced apart from each other by a distance selected to displace a volume of material of a body cavity. The retractor can be uses for holding open wounds or incisions, with trochars, or to displace anatomical features such as organs within a body cavity.
    Type: Grant
    Filed: January 17, 2018
    Date of Patent: July 16, 2019
    Assignees: President and Fellows of Harvard College, Soft Robotics Inc.
    Inventors: Kevin C. Galloway, Joshua Aaron Lessing
  • Patent number: 10353269
    Abstract: A fully confined dual frequency optical resonator configured for optical coupling to light having a first frequency ?1. The dual frequency optical resonator includes a plurality of alternating layer pairs configured in a grating configuration, each layer pair having a first layer formed of a first material and a second layer formed of a second material, the first material and second material being different materials. Each layer having a thickness different than a thickness of an adjacent layer to provide thereby aperiodic layer pairs, the thicknesses of adjacent layers being selected to create, via wave interference with each layer, optical resonances at the first frequency ?1 and a second frequency ?2 which is a harmonic of ?1, and to ensure a maximum spatial overlap between confined modes over the materials such that an overall quality factor Q of at least 1000 is achieved.
    Type: Grant
    Filed: February 27, 2017
    Date of Patent: July 16, 2019
    Assignees: THE TRUSTEES OF PRINCETON UNIVERSITY, PRESIDENT AND FELLOWS OF HARVARD COLLEGE, MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    Inventors: Alejandro Rodriguez, Zin Lin, Steven G. Johnson, Marko Loncar, Xiangdong Liang
  • Patent number: 10350264
    Abstract: Described herein are methods of modulating autophagic targeting of ferritin in a cell, wherein the method comprises modulating the level and/or activity of nuclear receptor coactivator 4 (NCOA4) in the cell. Also provided are related methods of treatment.
    Type: Grant
    Filed: March 27, 2015
    Date of Patent: July 16, 2019
    Assignees: Dana-Farber Cancer Institute, Inc., President and Fellows of Harvard College, Beth Israel Deaconess Medical Center, Inc., The Brigham & Women's Hospital, Inc.
    Inventors: Alec C. Kimmelman, Joseph D. Mancias, Jeffrey Wade Harper
  • Patent number: 10351568
    Abstract: Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.
    Type: Grant
    Filed: November 5, 2015
    Date of Patent: July 16, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Daniel J. Finley, Randall W. King, Byung-Hoon Lee, Min Jae Lee, Timothy C. Gahman
  • Publication number: 20190211293
    Abstract: Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one set of embodiments, droplets may be sorted using surface acoustic waves. The droplets may contain cells or other species. In some cases, the surface acoustic waves may be created using a surface acoustic wave generator such as an interdigitated transducer, and/or a material such as a piezoelectric substrate. The piezoelectric substrate may be isolated from the microfluidic substrate except at or proximate the location where the droplets are sorted, e.g., into first or second microfluidic channels. At such locations, the microfluidic substrate may be coupled to the piezoelectric substrate (or other material) by one or more coupling regions. In some cases, relatively high sorting rates may be achieved, e.g., at rates of at least about 1,000 Hz, at least about 10,000 Hz, or at least about 100,000 Hz, and in some embodiments, with high cell viability after sorting.
    Type: Application
    Filed: January 2, 2019
    Publication date: July 11, 2019
    Applicants: President and Fellows of Harvard College, Universit├Ąt Augsburg
    Inventors: David A. Weitz, Thomas Franke, Achim Wixforth, Lothar Schmid, Jeremy Agresti, Adam R. Abate
  • Patent number: 10343163
    Abstract: A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.
    Type: Grant
    Filed: September 20, 2017
    Date of Patent: July 9, 2019
    Assignees: The Brigham and Women's Hospital, Inc., President and Fellows of Harvard College, Vilnius University
    Inventors: Joseph Italiano, Linas Mazutis, Jonathan N. Thon, David A. Weitz
  • Patent number: 10344038
    Abstract: The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.
    Type: Grant
    Filed: April 29, 2016
    Date of Patent: July 9, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Yoshito Kishi, Wuming Yan, Jingwei Li, Zhanjie Li, Kenzo Yahata
  • Patent number: 10346748
    Abstract: Solution of a problem of determining values of a set of N problem variables x, makes use of a quantum processor that has a limited number of hardware elements for representing quantum bits and/or limitations on coupling between quantum bits. A method includes accepting a specification of the problem that includes a specification of a set of terms where each term corresponds to a product of at least three variables and is associated with a non-zero coefficient. A set of ancilla variables, each ancilla variable corresponding to a pair of problem variables, is determined by applying an optimization procedure to the specification of the set of the terms. The accepted problem specification is then transformed according to the determined ancilla variables to form a modified problem specification for use in configuring the quantum processor and solution of problem.
    Type: Grant
    Filed: July 25, 2014
    Date of Patent: July 9, 2019
    Assignee: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Alan Aspuru-Guzik, Ryan Babbush, Bryan O'Gorman
  • Patent number: 10346757
    Abstract: Techniques for use in connection with performing optimization using an objective function. The techniques include using at least one computer hardware processor to perform: beginning evaluation of the objective function at a first point; before evaluating the objective function at the first point is completed: identifying, based on likelihoods of potential outcomes of evaluating the objective function at the first point, a second point different from the first point at which to evaluate the objective function; and beginning evaluation of the objective function at the second point.
    Type: Grant
    Filed: May 30, 2014
    Date of Patent: July 9, 2019
    Assignees: President and Fellows of Harvard College, Socpra Sciences ET Genie S.E.C., The Governing Council of the University of Toronto
    Inventors: Ryan P. Adams, Roland Jasper Snoek, Hugo Larochelle
  • Publication number: 20190202707
    Abstract: Systems and methods for producing ammonia are described. In one embodiment, hydrogen, carbon dioxide, and nitrogen are dissolved in a solution. A glutamine synthetase inhibitor and autotrophic diazotroph bacteria are also placed in the solution.
    Type: Application
    Filed: June 14, 2017
    Publication date: July 4, 2019
    Applicant: President and Fellows of Harvard College
    Inventors: Brendan Cruz Colon, Chong Liu, Daniel G. Nocera, Pamela Ann Silver
  • Publication number: 20190203277
    Abstract: Provided herein, in some embodiments, are methods, compositions and kits for controlling nucleation and assembly of molecular nanostructures, microstructures and macrostructures.
    Type: Application
    Filed: August 2, 2017
    Publication date: July 4, 2019
    Applicants: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.
    Inventors: Dionis Minev, Christopher Wintersinger, William M. Shih
  • Publication number: 20190201479
    Abstract: The present disclosure provides, in some embodiments, compositions, kits, systems, and methods for reducing bacteria on a surface (e.g., a medical device) and preventing and/or treating a bacterial infection (e.g., urinary tract infection) in a subject using IdsD protein or a fragment thereof.
    Type: Application
    Filed: August 14, 2017
    Publication date: July 4, 2019
    Applicant: President and Fellows of Harvard College
    Inventors: Karine Gibbs, Christina Caroline Saak
  • Publication number: 20190201440
    Abstract: Disclosed herein are methods for generating universal MHC/HLA-compatible hematopoietic progenitor cells and methods for generating custom patient-specific MHC/HLA-compatible hematopoietic progenitor cells. Compositions comprising the universal and custom hematopoietic progenitor cells and therapeutic applications thereof are also disclosed.
    Type: Application
    Filed: February 17, 2017
    Publication date: July 4, 2019
    Applicants: THE GENERAL HOSPITAL CORPORATION, PRESIDENT AND FELLOWS OF HARVARD COLLEGE
    Inventors: Michael K. MANSOUR, David B. SYKES, David T. SCADDEN
  • Publication number: 20190203212
    Abstract: The present invention generally relates to methods and compositions used for the spatial and temporal control of gene expression that may use inducible transcriptional effectors. The invention particularly relates to inducible methods of altering or perturbing expression of a genomic locus of interest in a cell wherein the genomic locus may be contacted with a non-naturally occurring or engineered composition comprising a deoxyribonucleic acid (DNA) binding polypeptide.
    Type: Application
    Filed: March 8, 2019
    Publication date: July 4, 2019
    Applicants: Massachusetts Institute of Technology, The Broad Institute, Inc., President and Fellows of Harvard College
    Inventors: Feng Zhang, Mark Brigham, Le Cong, Silvana Konermann, Neville Sanjana
  • Patent number: 10336997
    Abstract: The invention provides systems, methods, reagents, apparatuses, vectors, and host cells for the continuous evolution of nucleic acids. For example, a lagoon is provided in which a population of viral vectors comprising a gene of interest replicates in a stream of host cells, wherein the viral vectors lack a gene encoding a protein required for the generation of infectious viral particles, and wherein that gene is expressed in the host cells under the control of a conditional promoter, the activity of which depends on a function of the gene of interest to be evolved. Some aspects of this invention provide evolved products obtained from continuous evolution procedures described herein. Kits containing materials for continuous evolution are also provided.
    Type: Grant
    Filed: June 21, 2016
    Date of Patent: July 2, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: David R. Liu, Kevin Michael Esvelt, Jacob Charles Carlson