公开(公告)号：US20240200044A1

公开(公告)日：2024-06-20

申请号：US18414114

申请日：2024-01-16

Applicant: President and Fellows of Harvard College

Inventor： David R. Liu ,  Basil Hubbard ,  Ahmed Hussein Badran

IPC: C12N9/22 ,  A61K48/00 ,  C12N15/62 ,  C12N15/85 ,  C12N15/90

CPC classification number: C12N9/22 ,  C12N15/62 ,  C12N15/8509 ,  C12N15/90 ,  A61K48/0066 ,  A61K48/0091

Abstract: 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. Some aspects of this disclosure provide engineered TALE domains and TALEs comprising such engineered domains, e.g., TALE nucleases (TALENs), TALE transcriptional activators, TALE transcriptional repressors, and TALE epigenetic modification enzymes, with altered 5′ nucleotide specificities of target sequences. Engineered TALEs that target ATM with greater specificity are also provided.

公开(公告)号：US12012633B2

公开(公告)日：2024-06-18

申请号：US17251451

申请日：2019-06-11

Applicant: The Broad Institute, Inc. ,  Massachusetts Institute of Technology ,  The Children's Medical Center Corporation ,  President and Fellows of Harvard College

Inventor： Leif S. Ludwig ,  Caleb A. Lareau ,  Jacob C. Ulirsch ,  Aviv Regev ,  Vijay G. Sankaran ,  Jason Buenrostro ,  Christoph Muus

IPC: C12Q1/68 ,  A61K45/06 ,  C12Q1/6827 ,  C12Q1/6869 ,  C12Q1/6886

CPC classification number: C12Q1/6869 ,  A61K45/06 ,  C12Q1/6827 ,  C12Q1/6886

Abstract: 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.

公开(公告)号：US20240185113A1

公开(公告)日：2024-06-06

申请号：US18512860

申请日：2023-11-17

Applicant: President and Fellows of Harvard College ,  QuEra Computing Incorporated

Inventor： Iris Cong ,  Shengtao Wang ,  Harry Jay Levine ,  Alexander Keesling Contreras ,  Mikhail D. Lukin

IPC: G06N10/70 ,  G06N10/20

CPC classification number: G06N10/70 ,  G06N10/20

Abstract: Error detection and correction in a quantum computer are provided. The quantum computer includes qubits encoding a plurality of data qudits and an ancilla qudit. The qubits encoding the plurality of data qudits are arranged into a grouping wherein the qubits encoding each of the data qudits are within an interaction distance of an interacting state of the qubits encoding the ancilla qudit. A leakage error of a first data qudit of the plurality of data qudits into the interacting state is detected by detecting a state of the ancilla qudit. Quantum states of the qudits are selected such that angular momentum selection rules prohibit mixing between the selected quantum states during a leakage error of one of the qudits into a noninteracting state. The leakage error is corrected by optical pumping of the noninteracting state, preserving coherence of the selected quantum states in the absence of the leakage error.

公开(公告)号：US11999775B2

公开(公告)日：2024-06-04

申请号：US16291829

申请日：2019-03-04

Applicant: Children's Medical Center Corporation ,  The General Hospital Corporation ,  President and Fellows of Harvard College

Inventor： Bob Carter ,  Jeng-Shin Lee ,  Szofia S. Bullain ,  Richard C. Mulligan

IPC: C07K14/71 ,  A61K48/00 ,  C07K14/475 ,  C12N15/11 ,  A61K35/42 ,  A61K38/00 ,  A61K39/00 ,  C12N15/113

CPC classification number: C07K14/71 ,  A61K48/00 ,  C07K14/475 ,  C12N15/11 ,  A61K35/42 ,  A61K38/00 ,  A61K39/001109 ,  C07K2317/24 ,  C07K2319/30 ,  C12N15/1136

Abstract: 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.

公开(公告)号：US20240175057A1

公开(公告)日：2024-05-30

申请号：US18425219

申请日：2024-01-29

Applicant: President and Fellows of Harvard College

Inventor： George M. Church ,  Prashant G. Mali ,  Kevin M. Esvelt

IPC: C12N15/90 ,  C12N9/22 ,  C12N15/10 ,  C12N15/11 ,  C12N15/113 ,  C12N15/63

CPC classification number: C12N15/907 ,  C12N9/22 ,  C12N15/102 ,  C12N15/11 ,  C12N15/113 ,  C12N15/635 ,  C12N2310/20 ,  C12N2310/3513 ,  C12Y301/00

Abstract: Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

公开(公告)号：US20240173430A1

公开(公告)日：2024-05-30

申请号：US17273688

申请日：2019-09-05

Applicant: The Broad Institute, Inc. ,  Baylor College of Medicine ,  Vanderbilt University ,  President and Fellows of Harvard College

Inventor： David R. Liu ,  Luke W. Koblan ,  Jonathan D. Brown ,  Charles Yang Lin

IPC: A61K48/00 ,  A61K38/17 ,  A61P9/00 ,  C12N7/00 ,  C12N9/22 ,  C12N9/80 ,  C12N15/11

CPC classification number: A61K48/005 ,  A61K38/1709 ,  A61P9/00 ,  C12N7/00 ,  C12N9/22 ,  C12N9/80 ,  C12N15/111 ,  C12N2310/20 ,  C12Y305/04004

Abstract: 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).

公开(公告)号：US11994687B2

公开(公告)日：2024-05-28

申请号：US17308905

申请日：2021-05-05

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE ,  TRUSTEES OF BOSTON UNIVERSITY

Inventor： Zhaoyi Li ,  Yao-Wei Huang ,  Peng Lin ,  Ji-Xin Cheng ,  Federico Capasso

IPC: G02B27/01 ,  G02B1/00 ,  G02B27/14 ,  G02B27/42 ,  G06T19/00

CPC classification number: G02B27/141 ,  G02B27/4227 ,  G06T19/006

Abstract: A display system includes an optical device configured according to constructive interference for a plurality of wavelengths at a focal length. The display system includes a fiber. The display system includes a controller configured to scan the fiber using a Lissajous scanning method to generate a display. The display can be disposed within a focal plane of the optical device. The controller is configured to modulate light intensity from the fiber. The controller can be configured to form a display image that passes through the optical device. The display system can include an optical combiner configured to reflect the display image from the optical device and form a virtual image. The optical device can be configured to magnify a display image from the display and form a virtual image.

公开(公告)号：US11989619B2

公开(公告)日：2024-05-21

申请号：US17681155

申请日：2022-02-25

Applicant: President and Fellows of Harvard College ,  Northwestern University

Inventor： George M. Whitesides ,  Albert Siangyoong Wong ,  Michael Johannes Fink ,  Khaled Abdelazim Mohamed ,  Alexei S. Ten ,  Milan M. Mrksich

IPC: G06K7/10 ,  B01J19/00 ,  G01N30/90 ,  G06K7/14 ,  G06K19/06

CPC classification number: G06K7/1434 ,  B01J19/0046 ,  G01N30/90 ,  G06K19/06037 ,  B01J2219/00605 ,  B01J2219/00659 ,  B01J2219/00695 ,  B01J2219/00725

Abstract: Storage media are provided. A substrate has an array of addressable locations thereon, each addressable location adapted to be physically associated with a collection of molecules, each collection comprising at least a first subcollection of molecules and a second subcollection of molecules. The molecules in the collection are selected from a set of unambiguously identifiable molecules, the set comprising at least a first subset of molecules and a second subset of molecules. Each molecule in the first subset is identifiable by a first physical property, and each molecule in the second subset is identifiable by a second physical property, different from the first physical property. Each molecule in the set is uniquely associated with a predetermined position in a numerical value, wherein the presence of the molecule in the collection indicates a predetermined digit at the associated position and the absence of said molecule in the collection indicates a zero at said associated position.

公开(公告)号：US11981956B2

公开(公告)日：2024-05-14

申请号：US16964527

申请日：2019-01-25

Applicant: President and Fellows of Harvard College

Inventor： Sinem K. Saka ,  Jocelyn Yoshiko Kishi ,  Peng Yin

IPC: C12Q1/682 ,  C12Q1/6804

CPC classification number: C12Q1/682 ,  C12Q1/6804

Abstract: Provided herein, in some embodiments, are compositions and methods for proximity detection of molecular targets.

公开(公告)号：US11980641B2

公开(公告)日：2024-05-14

申请号：US17366827

申请日：2021-07-02

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE

Inventor： Donald E. Ingber ,  Samira Musah

IPC: C12N5/071 ,  A61K35/22 ,  A61K35/545

CPC classification number: A61K35/22 ,  C12N5/0686 ,  A61K35/545 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/165 ,  C12N2501/385 ,  C12N2501/415 ,  C12N2501/727 ,  C12N2506/02 ,  C12N2506/45 ,  C12N2533/52

Abstract: Embodiments of various aspects described herein relate to methods, kits, and cell culture media for generation of podocytes from pluripotent stem (PS) cells, as well as cells produced by the same, and methods of use.