Patents Assigned to PRESIDENT & FELLOWS OF HARVARD
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Publication number: 20240124866Abstract: The disclosure provides methods and compositions for treating blood diseases/disorders, such as sickle cell disease, hemochromatosis, hemophilia, and beta-thalassemia. For example the disclosure provides therapeutic guide RNAs that target the promotor of HBG1/2 to generate point mutations that increase expression of fetal hemoglobin. As another example, the disclosure provides therapeutic guide RNAs that target mutations in HBB, Factor VIII, and HFE to treat sickle cell disease, beta-thalassemia, hemophilia and hemochromatosis. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins are in complex with nucleic acids, such as guide RNAs (gRNAs), which target the fusion proteins to a DNA sequence (e.g., an HBG1 or HBG2 protmoter sequence, or an HFE, GBB, or F8 gene sequence).Type: ApplicationFiled: September 1, 2023Publication date: April 18, 2024Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, Beam Therapeutics Inc.Inventors: David R. Liu, Nicole Marie Gaudelli, Michael S. Packer, Gregory Newby
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Patent number: 11959904Abstract: In a method for sensing translocation of a molecule through a nanopore, a molecule in a first fluidic solution in a first fluidic reservoir that is in direct fluidic connection with the nanopore is directed to a nanopore inlet and translocated through the nanopore to a nanopore outlet and through a fluidic passage that is in direct fluidic connection with the nanopore outlet, to a second fluidic solution in a second fluidic reservoir disposed in direct fluidic connection with the fluidic passage. The fluidic passage has at least one fluidic section in which a length of the fluidic section is greater than a width of the fluidic section. Translocation of the molecule through the nanopore is sensed by measuring the electrical potential local to the fluidic passage during the translocation of the molecule.Type: GrantFiled: August 31, 2020Date of Patent: April 16, 2024Assignee: President and Fellows of Harvard CollegeInventor: Ping Xie
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Patent number: 11957703Abstract: The invention provides methods of modulating and regulating NHD protein-protein interactions through nicotinamide mononucleotide, analogs and derivatives thereof, such as NAD+. Such modulation may be useful in methods of treating and preventing cancer, aging, cell death, radiation damage, radiation exposure, among others, may improve DNA repair, cell proliferation, cell survival, among others, and may increase the life span of a cell or protect it against certain stresses, among others.Type: GrantFiled: May 5, 2022Date of Patent: April 16, 2024Assignees: President and Fellows of Harvard College, Metro International Biotech, LLCInventors: David A. Sinclair, Jun Li, Karl D. Normington
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Patent number: 11959075Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.Type: GrantFiled: March 16, 2023Date of Patent: April 16, 2024Assignee: President and Fellows of Harvard CollegeInventors: Xiaowei Zhuang, Kok-Hao Chen, Alistair Boettiger, Jeffrey R. Moffitt, Siyuan Wang
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Publication number: 20240117312Abstract: Forced expression of a handful of transcription factors (TFs) can induce conversion between cell identities; however, the extent to which TFs can alter cell identity has not been systematic ally assessed. Here, we assembled a “human TFome,” a comprehensive expression library of 1,578 human TF clones with fall coverage of the major TF families. By systematically screening the human TFome, we identified many individual TFs that induce loss of human-induced-pluripotent-stem-cell (hiPSC) identity, suggesting a pervasive ability for TFs to alter cell identity. Using large-scale computational cell type classification trained on thousands of tissue expression pantiles, we identified cell types generated by these TFs with high efficiency and speed, without additional selections or mechanical perturbations. TF expression in adult human tissues only correlated with some of the cell lineage generated, suggesting more complexity than observation studies can explain.Type: ApplicationFiled: May 18, 2023Publication date: April 11, 2024Applicant: President and Fellows of Harvard CollegeInventors: Hon Man Alex Ng, George M. Church, Volker Busskamp
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Publication number: 20240117392Abstract: The technology described herein is directed to engineered chemoautotrophic bacteria and methods of producing triacylglycerides. Also described herein are systems or bioreactors comprising said engineered bacteria.Type: ApplicationFiled: February 9, 2022Publication date: April 11, 2024Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Shannon Noel NANGLE, Marika ZIESACK
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Publication number: 20240117033Abstract: The technology described herein is directed to compositions comprising antibodies and antibody reagent that binds specifically to Mfsd2A and method of using such compositions, e.g., to increase blood-brain barrier permeability in therapeutic methods.Type: ApplicationFiled: January 14, 2022Publication date: April 11, 2024Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Chengua GU, Benjamin ANDREONE, Urs LANGEN
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Publication number: 20240118554Abstract: Multi-wavelength light is directed to an optic including a substrate and metasurface optical components deposited on a surface of the substrate. The metasurface optical components comprise a pattern of silicon dielectric resonators with nonperiodic gap distances between adjacent dielectric resonators. Incident light directed to the metasurface optical components is scattered and phase-shifted by the configuration of the gap distances and the widths and thicknesses of the dielectric resonators. Each dielectric resonator has a rectangular cross-section such that a first phase shift is imparted for a transverse-electric (TE) component of the incident light and a second phase shift is imparted for a transverse-magnetic (TM) component of the incident light.Type: ApplicationFiled: July 11, 2023Publication date: April 11, 2024Applicant: President and Fellows of Harvard CollegeInventors: Francesco Aieta, Mikhail Kats, Patrice Genevet, Federico Capasso, Mohammadreza Khorasaninejad
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Publication number: 20240110159Abstract: The embodiments of the invention described herein relate to systems and methods for culturing and/or maintaining intestinal cells, tissues and/or organoids in vitro. The cells, tissues and/or organoids cultured according to the methods and systems described herein can mimic or reproduce natural intestinal epithelial structures and behavior as well as support co-culture of intestinal microflora.Type: ApplicationFiled: December 11, 2023Publication date: April 4, 2024Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Donald E. INGBER, Hyun Jung Kim
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Publication number: 20240113028Abstract: An interconnection layer structure including a two-dimensional (2D) material, an electronic device including the interconnection layer structure, and an electronic apparatus including the electronic device are disclosed. The interconnection layer structure may include a first interconnection layer, and a work function modulation layer directly on one surface of the first interconnection layer. The first interconnection layer may include a metal layer, and the work function modulation layer may be a two-dimensional (2D) material layer that includes ruthenium (Ru).Type: ApplicationFiled: September 21, 2023Publication date: April 4, 2024Applicants: Samsung Electronics Co., Ltd., President and Fellows Of Harvard CollegeInventors: Yeonchoo CHO, Elise BRUTSCHEA, Hongkun PARK, Minsu SEOL
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Publication number: 20240108709Abstract: The present invention provides vaccine compositions and methods of producing such compositions. Other embodiments of the invention include methods of treating a pathogen infection, methods of vaccinating a subject against a pathogen infection, and methods for treating an antibiotic-resistance bacterial infection in a subject in need thereof. In further embodiments, the invention includes methods of decreasing the level of a pathogen in a subject having a pathogen infection, methods of increasing the surviving rate of a subject having a pathogen infection, methods of reducing the level of pain associated with a pathogen infection, and methods of reducing the level of distress associated with a pathogen infection in a subject in need thereof. Novel scaffold compositions and opsonin-bound or lectin-bound pathogen compositions, and uses thereof, are also provided herein.Type: ApplicationFiled: March 20, 2023Publication date: April 4, 2024Applicant: President and Fellows of Harvard CollegeInventors: Michael Super, Edward J. Doherty, Mark Joseph Cartwright, Des White, Alexander Stafford, Omar Abdel-Rahman Ali, Amanda Graveline, Donald E. Ingber, David J. Mooney, Benjamin Seiler
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Publication number: 20240112755Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids or other desired targets, for instance, within cells or tissues. In one aspect, a sample is exposed to a plurality of nucleic acid probes that are determined within the sample. In some cases, however, background fluorescence or off-target binding may make it more difficult to determine properly bound nucleic acid probes. Accordingly, other components of the samples that may be contributing to the background, such as proteins, lipids, and/or other non-targets, may be “cleared” from the sample to improve determination. However, in certain embodiments, nucleic acids or other desired targets may be prevented from also being cleared, e.g., using polymers or gels within the sample. Other aspects are generally directed to compositions or kits involving such systems, methods of using such systems, or the like.Type: ApplicationFiled: May 1, 2023Publication date: April 4, 2024Applicant: President and Fellows of Harvard CollegeInventors: Xiaowei Zhuang, Jeffrey R. Moffitt, Junjie George Hao, Tian Lu
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Publication number: 20240113211Abstract: A semiconductor device may include a two-dimensional (2D) material having a semiconductor characteristic, a conductive layer on a first surface of the 2D material layer, and an alignment adjusting layer on a second surface of the 2D material layer. The second surface may be different from the first surface. The alignment adjusting layer may adjust an energy-band alignment between the 2D material layer and the conductive layer.Type: ApplicationFiled: September 27, 2023Publication date: April 4, 2024Applicants: Samsung Electronics Co., Ltd., President and Fellows Of Harvard CollegeInventors: Yeonchoo CHO, Elise BRUTSCHEA, Philip KIM, Hongkun PARK, Minsu SEOL
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Publication number: 20240110166Abstract: Provided herein are systems, compositions, and methods of introducing protective and/or loss-of-function variants of CCR5 and CCR2. Variants may be introduced using a CRISPR/Cas9-based nucleobase editor or other guide nucleotide sequence-programmable DNA binding protein domain-based fusion protein described herein. Further provided herein are compositions and methods of preventing and treating conditions related to HIV infection and progression as well as to AIDS.Type: ApplicationFiled: October 10, 2023Publication date: April 4, 2024Applicant: President and Fellows of Harvard CollegeInventors: Juan Pablo Maianti, David R. Liu
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Patent number: 11944429Abstract: Systems and methods are disclosed to objectively identify sub-second behavioral modules in the three-dimensional (3D) video data that represents the motion of a subject. Defining behavioral modules based upon structure in the 3D video data itself— rather than using a priori definitions for what should constitute a measurable unit of action— identifies a previously-unexplored sub-second regularity that defines a timescale upon which behavior is organized, yields important information about the components and structure of behavior, offers insight into the nature of behavioral change in the subject, and enables objective discovery of subtle alterations in patterned action. The systems and methods of the invention can be applied to drug or gene therapy classification, drug or gene therapy screening, disease study including early detection of the onset of a disease, toxicology research, side-effect study, learning and memory process study, anxiety study, and analysis in consumer behavior.Type: GrantFiled: March 8, 2023Date of Patent: April 2, 2024Assignee: President and Fellows of Harvard CollegeInventors: Sandeep Robert Datta, Alexander B. Wiltschko, Matthew J. Johnson
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Patent number: 11946055Abstract: Disclosed herein are methods, compositions, and kits for engineering proteins using error-prone orthogonal replication (epOrthoRep) and yeast surface display (YSD).Type: GrantFiled: December 9, 2021Date of Patent: April 2, 2024Assignees: The Regents of the University of California, President and Fellows of Harvard CollegeInventors: Chang C. Liu, Alon Wellner, Ziwei Zhong, Arjun Ravikumar, Andrew Kruse, Conor Thomas McMahon
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Patent number: 11946925Abstract: In a nanopore sensor, a nanopore disposed in a support structure has a nanopore diameter and nanopore resistance, RPore. A fluidic passage, disposed in fluidic connection between a first fluidic reservoir and the nanopore, has a cross-sectional extent, along at least a portion of the fluidic passage length, that is greater than the diameter of the nanopore and that is less than the fluidic passage length. The fluidic passage has a fluidic passage resistance, RFP, of at least about 10% of the nanopore resistance, RPore, and no more than about 10 times the nanopore resistance, RPore. The nanopore is disposed in fluidic connection between the fluidic passage and a second fluidic reservoir. At least one electrical transduction element is disposed at the fluidic passage and electrically connected to produce an indication of electrical potential local to the fluidic passage.Type: GrantFiled: April 12, 2022Date of Patent: April 2, 2024Assignee: President and Fellows of Harvard CollegeInventor: Ping Xie
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Publication number: 20240100767Abstract: In one aspect, the present disclosure provides a nozzle for a 3D printing system. The nozzle may include a flowpath with a material inlet and a material outlet. The nozzle may further include a valve in fluid communication with the flowpath between the material inlet and the material outlet, where the valve includes a closed state and an open state, where in the closed state the valve obstructs the flowpath between the material inlet and the material outlet, and where in the open state the material inlet is in fluid communication with the material outlet. The nozzle may further include a compensator in fluid communication with the flowpath, where the compensator includes a contracted state associated with the open state of the valve and an expanded state associated with the closed state of the valve.Type: ApplicationFiled: September 6, 2023Publication date: March 28, 2024Applicant: President and Fellows of Harvard CollegeInventors: Jennifer A. LEWIS, Mark A. Skylar-Scott, Jochen Mueller
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Publication number: 20240101967Abstract: Described herein are compositions and methods for generating a viable cell that expresses at least one or more woolly mammoth genes. Also described herein are compositions and methods for generating an embryo, blastula, oocyte, or non-human organism that expresses one or more woolly mammoth genes.Type: ApplicationFiled: December 10, 2021Publication date: March 28, 2024Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: George M. Church, Eriona Hysolli, Jessica Weber, Pranam Chatterjee, Cory Smith
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Patent number: 11940399Abstract: Systems and methods of quantum sensing include obtaining information regarding a target signal in electronic spin states of quantum defects in an ensemble of quantum defects, mapping the information regarding the target signal from the electronic spin states of the quantum defects to corresponding nuclear spin states associated with the quantum defects, applying a light pulse to the ensemble of quantum defects to reset the electronic spin states of the quantum defects, and repeating a readout stage a plurality of times within a readout duration. The readout stage includes mapping the information regarding the target signal back from the nuclear spin states to the corresponding electronic spin states and applying a data acquisition readout pulse to optically measure the electronic spin states of the quantum defects.Type: GrantFiled: June 1, 2022Date of Patent: March 26, 2024Assignees: University of Maryland, College Park, The President and Fellows of Harvard CollegeInventors: Ronald Walsworth, Nithya Arunkumar, Connor Hart, Dominik Bucher, David Glenn