Patents Assigned to PRESIDENT AND FELLOWS OF HARVARD COLLEGES
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Publication number: 20240209072Abstract: A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of secreted aP2, secretion of aP2, or a serum aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Exemplary compositions inhibit cellular secretion of aP2 or bind to circulating aP2, thereby reducing the level or activity of aP2 in blood or serum.Type: ApplicationFiled: June 26, 2023Publication date: June 27, 2024Applicant: President and Fellows of Harvard CollegeInventors: Gokhan S. Hotamisligil, Haiming Cao
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Patent number: 12018321Abstract: Methods of detecting, probing, mapping and directed sequencing of target nucleic acids are provided using a guide RNA and a Cas9 protein. Methods for detecting the binding of the guide RNA/Cas9 complex to a target nucleic acid where the guide RNA includes a 3? tail sequence that can hybridize to a probe are provided. Methods for detecting the binding of the guide RNA/Cas9 complex to a target nucleic acid where the complex is physically detected are provided.Type: GrantFiled: December 8, 2020Date of Patent: June 25, 2024Assignee: President and Fellows of Harvard CollegeInventors: George M. Church, Frederic Vigneault, Kalim U. Mir
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Patent number: 12018272Abstract: 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: GrantFiled: April 6, 2023Date of Patent: June 25, 2024Assignee: President and Fellows of Harvard CollegeInventors: George M. Church, Prashant G. Mali, Luhan Yang
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Patent number: 12018275Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues of organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provide dare methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.Type: GrantFiled: February 25, 2020Date of Patent: June 25, 2024Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Feng Zhang, Le Cong, Fei Ran
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Publication number: 20240200044Abstract: Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is that the 5? nucleotide of the target is specific for thymine (T). TALE domains with alternative 5? nucleotide specificities could expand the scope of DNA target sequences that can be bound by TALEs. Another drawback of TALEs is their tendency to bind and cleave off-target sequence, which hampers their clinical application and renders applications requiring high-fidelity binding unfeasible. This disclosure provides methods and strategies for the continuous evolution of proteins comprising DNA-binding domains, e.g., TALE domains. In some aspects, this disclosure provides methods and strategies for evolving such proteins under positive selection for a desired DNA-binding activity and/or under negative selection against one or more undesired (e.g., off-target) DNA-binding activities.Type: ApplicationFiled: January 16, 2024Publication date: June 20, 2024Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, Basil Hubbard, Ahmed Hussein Badran
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Publication number: 20240201179Abstract: Provided herein are fluorogenic sensors which can be used to detect targets (e.g., antigens). In general, the fluorogenic sensors provided herein comprise a protein (e.g., antibody, nanobody, mini-protein) and a fluorogenic small molecule conjugated to the target-binding domain (e.g., antigen-binding domain) of the protein. Upon binding of the protein to said target (e.g., antigen), the fluorogenic small molecule may increase or decrease in fluorescence or exhibit a change in fluorescence lifetime (i.e., “turn on”), thereby indicating the presence of the target (e.g., antigen).Type: ApplicationFiled: March 25, 2022Publication date: June 20, 2024Applicant: President and Fellows of Harvard CollegeInventors: Erkin Kuru, George M. Church, Janathan Rittichier, Isaac Han, Helena de Puig Guixe
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Patent number: 12012633Abstract: Embodiments disclosed herein provide methods of using somatic mutations in mitochondrial genomes to retrospectively infer cell lineages in native contexts and to serve as genetic barcodes to measure clonal dynamics in complex cellular populations. Further, somatic mutations in mitochondrial DNA (mtDNA) are tracked by single cell genomic approaches for simultaneous analysis of single cell lineage and state. Applicants further show that mitochondrial mutations can be readily detected with contemporary single cell transcriptomic and epigenomic technologies to concomitantly capture gene expression profiles and chromatin accessibility, respectively.Type: GrantFiled: June 11, 2019Date of Patent: June 18, 2024Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, The Children's Medical Center Corporation, President and Fellows of Harvard CollegeInventors: Leif S. Ludwig, Caleb A. Lareau, Jacob C. Ulirsch, Aviv Regev, Vijay G. Sankaran, Jason Buenrostro, Christoph Muus
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Patent number: 12012670Abstract: This disclosure provides methods for monitoring an immune response. Methods comprise linking a polynucleotide sequence encoding a heavy chain variable region and a polynucleotide sequence encoding a light chain variable region from a single lymphocyte from a biological sample obtained before an immune response and linking a polynucleotide sequence encoding a heavy chain variable region and a polynucleotide sequence encoding a light chain variable region from a single lymphocyte from a biological sample obtained during or after an immune response. Methods further comprise performing high-throughput sequencing of the linked (paired) sequences from before the immune response and from during or after the immune response, and comparing the resulting sequence reads.Type: GrantFiled: July 17, 2019Date of Patent: June 18, 2024Assignee: President and Fellows of Harvard CollegeInventors: George M. Church, Francois Vigneault, Uri Laserson, Ido Bachelet
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Patent number: 12014246Abstract: Systems and methods are disclosed for making a quantum network node. A plurality of scoring function F values are calculated for an array of at least two photonic crystal cavity unit cells, each having a lattice constant a and a hole having a length Hx and a width Hy. A value of a, a value of Hx, and a value of Hy are selected for which a scoring function value is at a maximum. A waveguide region and the array of at least two photonic crystal cavity unit cells based on the selected values are formed on a substrate. At least one ion between a first photonic crystal cavity unit cell and a second photonic crystal cavity unit cell are implanted and annealed into a quantum defect. A coplanar microwave waveguide is formed on the substrate in proximity to the array of at least two photonic crystal cavity unit cells.Type: GrantFiled: July 16, 2020Date of Patent: June 18, 2024Assignee: President and Fellows of Harvard CollegeInventors: Mihir Keshav Bhaskar, Denis D. Sukachev, Christian Thieu Nguyen, Bartholomeus Machielse, David S. Levonian, Ralf Riedinger, Mikhail D. Lukin, Marko Loncar
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Patent number: 12004948Abstract: A replacement heart valve device is disclosed. In some embodiments, the device includes a frame coupled to one or more leaflets that are moveable between open and closed configurations. In some embodiments, the frame comprises at least two frame sections that join at a pair of commissural posts. In some embodiments, the device may be geometrically accommodating to adapt to different vasculature shapes and sizes and/or to be able to change size while implanted within a growing patient.Type: GrantFiled: June 2, 2020Date of Patent: June 11, 2024Assignees: Children's Medical Center Corporation, President and Fellows of Harvard College, Massachusetts Institute of TechnologyInventors: Sophie-Charlotte Hofferberth, Pedro J. del Nido, Elazer R. Edelman, Peter E. Hammer, Christopher Payne
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Patent number: 12005631Abstract: A printhead comprises a plurality of ink cartridges and a nozzle, where the nozzle and the ink cartridges are configured to rotate together about an axis during printing. The nozzle includes a nozzle body comprising an inlet end, an outlet end, and one or more internal passageways extending through the nozzle body from the inlet end to the outlet end. The one or more internal passageways terminate at one or more outlets at or near the outlet end. The nozzle also includes plurality of nozzle inlets at the inlet end for delivery of flowable inks into the internal passageways, where each nozzle inlet is in fluid communication with a dispensing end of one of the ink cartridges.Type: GrantFiled: November 8, 2022Date of Patent: June 11, 2024Assignee: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Natalie M. Larson, Jochen Mueller, Jennifer A. Lewis
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Patent number: 12006520Abstract: Engineered nucleases are promising tools for genome manipulation and determining off-target cleavage sites of these enzymes is of great interest. This disclosure provides in vitro selection methods that interrogate 1011 DNA sequences for their ability to be cleaved by active nucleases, e.g., ZFNs and TALENs. The method revealed hundreds of thousands of DNA sequences that can be cleaved in vitro by two ZFNs, CCR5-224 and VF2468, which target the endogenous human CCR5 and VEGF-A genes, respectively. Analysis of the identified sites in cultured human cells revealed CCR5-224-induced mutagenesis at nine off-target loci. This disclosure provides an energy compensation model of ZFN specificity in which excess binding energy contributes to off-target ZFN cleavage. It was also observed that TALENs can achieve cleavage specificity similar to or higher than that observed in ZFNs.Type: GrantFiled: June 14, 2019Date of Patent: June 11, 2024Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, John Paul Guilinger, Vikram Pattanayak
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Patent number: 11999947Abstract: The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA. 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 further comprise a nuclear localization sequence (NLS), and/or an inhibitor of base repair, such as, a nuclease dead inosine specific nuclease (dISN).Type: GrantFiled: February 24, 2023Date of Patent: June 4, 2024Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, Nicole Gaudelli
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Patent number: 11998593Abstract: 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: GrantFiled: May 18, 2020Date of Patent: June 4, 2024Assignees: President and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.Inventors: Omar Abdel-Rahman Ali, David J. Mooney, Glenn Dranoff
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Patent number: 11999931Abstract: A microfluidic device for processing cells for the intracellular delivery of molecules or other cargo includes a plurality of microchannels disposed in a substrate or chip and fluidically coupled to an inlet configured to receive a solution containing the cells and the molecules or other cargo to be delivered intracellularly to the cells. Each of the plurality of microchannels has one or more constriction regions therein, wherein the constriction regions comprise an omniphobic, superhydrophilic, or superhydrophobic surface. In some embodiments, multiple microfluidic devices operating in parallel are used to process large numbers of cells. The device and method has particularly applicability to delivering gene-editing molecules intracellularly to cells.Type: GrantFiled: August 19, 2017Date of Patent: June 4, 2024Assignees: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, PRESIDENT AND FELLOWS OF HARVARD COLLEGE, THE BRIGHAM AND WOMEN'S HOSPITAL, INC.Inventors: Steven J. Jonas, Paul S. Weiss, Xu Hou, Joanna Aizenberg, Alireza Khademhosseini
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Patent number: 11999775Abstract: Provided are chimeric VEGF-binding proteins and nucleic acids (e.g., a vector) encoding chimeric VEGF-binding proteins, methods and host cells for producing these proteins and nucleic acids, and pharmaceutical compositions containing these proteins and nucleic acids. Also provided are methods of treating an angiogenic disease or disorder that include administering at least one of the chimeric VEGF-binding proteins or at least one of the nucleic acids (e.g., a vector) encoding a chimeric VEGF-binding protein.Type: GrantFiled: March 4, 2019Date of Patent: June 4, 2024Assignees: Children's Medical Center Corporation, The General Hospital Corporation, President and Fellows of Harvard CollegeInventors: Bob Carter, Jeng-Shin Lee, Szofia S. Bullain, Richard C. Mulligan
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Patent number: 11998270Abstract: The invention provides methods of diagnosing neuropathic corneal pain by the detection of neuromas, such as micro-neuromas, on the cornea. The invention also features systems for detecting the presence of anatomical features located on an ocular tissue surface that may be a marker for neuropathic corneal pain. The systems feature an in vivo confocal microscope and a computer N programmed with a neural network to automate the analysis of the microscope images. The invention provides methods of using the system to identify a micro-neuroma in images collected of an ocular surface and methods of diagnosing neuropathic corneal pain and monitoring treatment of neuropathic corneal pain using a system of the invention.Type: GrantFiled: April 26, 2019Date of Patent: June 4, 2024Assignees: Tufts Medical Center, Inc., President and Fellows of Harvard CollegeInventors: Pedram Hamrah, Neslihan Dilruba Koseoglu, Andrew Beam
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Publication number: 20240173430Abstract: The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA to treat Hutchin-son-Gilford progeria syndrome (HOPS). The disclosure also provides fusion proteins, guide RNAs and compositions comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA, for example in a LNA gene. In some embodiments, adenosine deaminases provided herein are used to correct a C1824T mutation in LMNA. In some embodiments, the methods and compositions provided herein are used to treat Hutchinson-Gilford progeria syndrome (HGPS).Type: ApplicationFiled: September 5, 2019Publication date: May 30, 2024Applicants: The Broad Institute, Inc., Baylor College of Medicine, Vanderbilt University, President and Fellows of Harvard CollegeInventors: David R. Liu, Luke W. Koblan, Jonathan D. Brown, Charles Yang Lin
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Publication number: 20240175081Abstract: The present invention generally relates to imaging cells, for example, to determine phenotypes and/or genotypes in populations of cells. In some aspects, cells may be analyzed, e.g., imaged, to determine their phenotype, and their genotypes may be determined by exposing the cells to nucleic acid probes, e.g., as in smFISH. MERFISH, FISH, in situ hybridization, or other suitable techniques. In some cases, the cells may be exposed to a nucleic acid comprising an identification portion, which may be used to distinguish the cells from each other. In some embodiments, the cells may be exposed to a nucleic acid comprising an expression portion, e.g. a gene, or coding region for a non-translated RNA, etc., that when expressed, produces a protein, RNA, DNA, or the like that may alter the phenotype of the cell or the variable nucleic acid sequence can consist of promoters, gene regulatory elements, transcription factor binding sites, Cas9 guide RNA coding regions, etc. that otherwise alter the phenotype of the cell.Type: ApplicationFiled: September 6, 2023Publication date: May 30, 2024Applicant: President and Fellows of Harvard CollegeInventors: Xiaowei Zhuang, George Alexander Emanuel, Jeffrey R. Moffitt
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Patent number: 11994507Abstract: A first fluidic solution having a first ionic concentration is provided in a first fluidic reservoir in direct fluidic connection with a nanopore. A second fluidic solution, having a second ionic concentration, is provided in a second fluidic reservoir disposed in fluidic connection with the nanopore through a fluidic passage having at least one fluidic section in which the section length is greater than the section width. The electrical potential local to the fluidic passage is measured, and the resistance of both the fluidic passage the nanopore are determined based on the fluidic passage electrical potential. The fluidic passage resistance is compared with the nanopore resistance and at least one of the first and second ionic concentrations is adjusted based on the comparison. The measuring, determining, comparing, and adjusting steps are conducted until the fluidic passage resistance is between about 0.1 times and about 10 times the nanopore resistance.Type: GrantFiled: August 31, 2020Date of Patent: May 28, 2024Assignee: President and Fellows of Harvard CollegeInventor: Ping Xie