Patents Assigned to PRESIDENT & FELLOWS OF HARVARD
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Patent number: 11939571Abstract: Expressing guide nucleic acids (e.g., gRNA) from the same oligonucleotide that contains donor sequence permits the high efficiency, simultaneous transformation of a population of cells with both substrates. Using oligonucleotide chip array technology, one can construct thousands of oligonucleotides with customized gRNA and donor sequence in a cost effective manner. In combination, one can efficiently modify endogenous and exogenous genes.Type: GrantFiled: June 12, 2017Date of Patent: March 26, 2024Assignees: President and Fellows of Harvard College, The General Hospital CorporationInventors: Xiaoge Guo, Alejandro Chavez, Max Schubert, Eric Kelsic
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Patent number: 11940441Abstract: Provided herein relates to systems and methods for producing and using a body having a central channel separated by one or more membranes. The membrane(s) are configured to divide the central channel into at least one mesochannel and at least one microchannel. The height of the mesochannel is substantially greater than the height of the microchannel. A gaseous fluid can be applied through the mesochannel while a liquid fluid flowing through the microchannel. The systems and methods described herein can be used for various applications, including, e.g., growth and differentiation of primary cells such as human lung cells, as well as any other cells requiring low shear and/also stratified structures, or simulation of a microenvironment in living tissues and/or organs (to model physiology or disease states, and/or to identify therapeutic agents and/or vaccines). The systems and methods can also permit co-culture with one or more different cell types.Type: GrantFiled: September 11, 2020Date of Patent: March 26, 2024Assignee: President and Fellows of Harvard CollegeInventors: Donald E. Ingber, Kambez Hajipouran Benam, Remi Villenave, Geraldine A. Hamilton, Bryan Hassell, Christopher D. Hinojosa, Carolina Lucchesi
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Publication number: 20240094439Abstract: An optical component can include a substrate. The optical component can include a metasurface disposed on the substrate. The metasurface can include one or more linearly birefringent elements. A spatially-varying Jones matrix and a far-field of the metasurface can define a transfer function of the metasurface configured to generate a controlled response in the far-field according to polarization of light incident on the metasurface.Type: ApplicationFiled: December 27, 2021Publication date: March 21, 2024Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Noah A. RUBIN, Mohammad Aun Abbas ZAIDI, Federico CAPASSO
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Publication number: 20240093190Abstract: The present disclosure provides compositions and methods for inhibiting viral pathogenesis by targeting long noncoding ribonucleic acids.Type: ApplicationFiled: January 18, 2022Publication date: March 21, 2024Applicant: President and Fellows of Harvard CollegeInventors: Longlong Si, Haiqing Bai, Rachelle Pranti-Baun, Donald E. Ingber
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Publication number: 20240093156Abstract: The disclosure provides methods and compositions for reprogramming fibroblasts into limb progenitors.Type: ApplicationFiled: August 15, 2023Publication date: March 21, 2024Applicants: President and Fellows of Harvard College, The Brigham and Women's Hospital, Inc.Inventors: Clifford J. Tabin, Yuji Atsuta, Alan R. Rodrigues, ChangHee Lee, Olivier Pourquie
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Patent number: 11932884Abstract: 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: GrantFiled: March 21, 2022Date of Patent: March 19, 2024Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, Kevin Tianmeng Zhao, Yongjoo Kim
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Publication number: 20240082420Abstract: Methods, systems, compositions and strategies for the delivery of RNA into cells in vivo, ex vivo, or in vitro via ARMMs are provided. In some aspects, ARMMs containing fusion proteins of ARRDC1 fused to an RNA binding protein or an RNA binding protein fused to a WW domain are provided. In some aspects, ARMMs containing binding RNAs associated with cargo RNAs are provided. In other aspects, cargo RNAs associated with a binding RNA, such as a TAR element, are loaded into ARMMs via ARRDC1 fusion proteins containing an RNA binding protein, such as trans-activator of transcription (Tat) protein.Type: ApplicationFiled: June 28, 2023Publication date: March 14, 2024Applicant: President and Fellows of Harvard CollegeInventor: Quan Lu
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Publication number: 20240084364Abstract: 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: ApplicationFiled: August 17, 2023Publication date: March 14, 2024Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Feng ZHANG, Bernd ZETSCHE, Jonathan S. GOOTENBERG, Omar O. ABUDAYYEH, Ian SLAYMAKER
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Patent number: 11925933Abstract: The present invention generally relates to microfluidic devices. In some aspects, various entities, such as droplets or particles, may be contained within a microfluidic device, e.g., within collection chambers or other locations within the device. In some cases, the entities may be released from such locations, e.g., in a sequential pattern, or an arbitrary pattern. In some cases, the entities may be imaged, reacted, analyzed, etc. while contained within the collection chambers. Other aspects are generally directed to methods of making or using such devices, kits involving such devices, or the like.Type: GrantFiled: April 14, 2017Date of Patent: March 12, 2024Assignee: President and Fellows of Harvard CollegeInventors: David A. Weitz, Kiryakos S. Mutafopulos, Thomas Hufnagel
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Publication number: 20240076652Abstract: 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: ApplicationFiled: February 24, 2023Publication date: March 7, 2024Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, Nicole Gaudelli
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Publication number: 20240075012Abstract: The present disclosure provides compositions and methods for inhibiting respiratory viral infections, inflammatory diseases, and/or respiratory inflammation.Type: ApplicationFiled: August 11, 2023Publication date: March 7, 2024Applicant: President and Fellows of Harvard CollegeInventors: Haiqing Bai, Longlong Si, Rachelle Prantil-Baun, Donald E. Ingber
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Publication number: 20240077502Abstract: Evolved sortases exhibiting enhanced reaction kinetics and/or altered substrate preferences are provided herein, for example evolved sortases that bind recognitions motifs comprising a LMVGG [SEQ ID NO: 3] sequence. Also provided are methods (e.g., orthogonal transpeptidation and diagnostics methods) for using such sortases.Type: ApplicationFiled: January 11, 2022Publication date: March 7, 2024Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, The Brigham and Women's Hospital Inc.Inventors: David R. Liu, Christopher J Podracky, Chihui An, Dominic Walsh
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Patent number: 11920150Abstract: Described herein are targeting moieties that can be capable of specifically targeting muscle cells and can include an n-mer motif. In some embodiments, the n-mer motif contains an RGD motif. Also described herein are vector systems, particles, polypeptides that can encode and/or contain one or more targeting moieties. Also described herein are methods of delivering a cargo to a cell, such as a muscle cell, using one or more of the targeting moieties described herein.Type: GrantFiled: March 29, 2022Date of Patent: March 5, 2024Assignees: The Broad Institute, Inc., President and Fellows of Harvard College, Massachusetts Institute of TechnologyInventors: Pardis Sabeti, Mohammadsharif Tabebordbar, Simon Ye
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Patent number: 11923581Abstract: The invention features redox flow batteries and compound useful therein as negolytes or posolytes. The batteries and compounds are advantageous in terms of being useable in water solutions at neutral pH and have extremely high capacity retention. Suitable negolytes are diquaternized bipyridines, suitable posolytes are water-soluble ferrocene derivatives.Type: GrantFiled: August 14, 2017Date of Patent: March 5, 2024Assignee: President and Fellows of Harvard CollegeInventors: Roy G. Gordon, Michael J. Aziz, Eugene Beh
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Patent number: 11920181Abstract: Some aspects of this disclosure provide strategies, methods, and reagents for determining nuclease target site preferences and specificity of site-specific endonucleases. Some methods provided herein utilize a novel “one-cut” strategy for screening a library of concatemers comprising repeat units of candidate nuclease target sites and constant insert regions to identify library members that can been cut by a nuclease of interest via sequencing of an intact target site adjacent and identical to a cut target site. Some aspects of this disclosure provide strategies, methods, and reagents for selecting a site-specific endonuclease based on determining its target site preferences and specificity. Methods and reagents for determining target site preference and specificity are also provided.Type: GrantFiled: January 27, 2021Date of Patent: March 5, 2024Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, Vikram Pattanayak
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Patent number: 11918984Abstract: Disclosed are compounds, methods, reagents, systems, and kits for the preparation and utilization of monomeric or polymeric metal-based compounds. These metal-based compounds are organometallic catalysts composed of substituted dipyrrin ligands bound to transition metals. C—H bond functionalization catalysis can be performed with the disclosed organometallic catalysts to yield C—N bonds to generate substituted bicyclic, spiro, and fused nitrogen-containing heterocycles, all common motifs in various pharmaceutical and bioactive molecules.Type: GrantFiled: September 19, 2019Date of Patent: March 5, 2024Assignee: President and Fellows of Harvard CollegeInventors: Theodore Alexander Betley, Alexandre Mikhailine, Claudia Kleinlein, Yuyang Dong, Yunjung Baek
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Patent number: 11919971Abstract: This disclosure provides, e.g., methods for coupling Formation of Surface Carboxylates on PES an entity to a solid substrate. The method can comprise treating the with Exposure Time substrate with a plasma, e.g., a CO2 plasma, to increase its reactivity. The entity can be, e.g., a biological polymer that binds a microbe. Substrates produced by these methods can be used in a variety of applications, including hemodialysis and diagnostic assays.Type: GrantFiled: May 16, 2017Date of Patent: March 5, 2024Assignee: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Daniel Christopher Leslie, Thomas Doyle, Anna Waterhouse, Melissa Rodas, Alexander L. Watters, Michael Super, Donald E. Ingber
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Publication number: 20240067957Abstract: Genetic circuits that control transgene expression in response to pre-defined transcriptional cues would enable the development of smart therapeutics. The present disclosure relates to engineered programmable single-transcript RNA sensors in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert trigger hybridization into a translational output. This system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. Amplification is mediated by the expression of a hyperactive, minimal ADAR variant and its recruitment to the edit site via an orthogonal RNA targeting mechanism. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint. The circuits and systems disclosed herein leverage an ability to detect single nucleotide polymorphisms and modulate translation in response to endogenous transcript levels in mammalian cells.Type: ApplicationFiled: June 22, 2023Publication date: February 29, 2024Applicants: Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: James J. Collins, Raphael Gayet, Katherine IIia, Shiva Razavi, Nathaniel Tippens, Kehan Zhang, Jack Chen, Jonathan Chen, Makoto Lalwani
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Patent number: 11913872Abstract: An apparatus for measuring a characteristic of a sample using a centrifuge and optical components is disclosed. The centrifuge may be a standard benchtop centrifuge. The optical components may be sized and dimensioned to fit, along with the sample, inside the centrifuge.Type: GrantFiled: February 4, 2021Date of Patent: February 27, 2024Assignees: President and Fellows of Harvard College, Children's Medical Center CorporationInventors: Darren Yang, Andrew Ward, Wesley Philip Wong, Kenneth Anders Halvorsen
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Patent number: 11913040Abstract: 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: GrantFiled: June 23, 2021Date of Patent: February 27, 2024Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, Basil Hubbard, Ahmed Hussein Badran