公开(公告)号：US20240165145A1

公开(公告)日：2024-05-23

申请号：US18244849

申请日：2023-09-11

申请人： The Regents of the University of California

发明人： Catriona JAMIESON ,  Maria Anna ZIPETO ,  Leslie ROBERTSON ,  Larisa BALAIAN ,  Nathaniel Delos SANTOS ,  Qingfei JIANG

IPC分类号： A61K31/7076 ,  A61K31/506 ,  A61P35/00 ,  A61P35/02 ,  C12N5/095 ,  C12N15/113 ,  C12Q1/6851 ,  C12Q1/686 ,  C12Q1/6886 ,  G01N33/574

CPC分类号： A61K31/7076 ,  A61K31/506 ,  A61P35/00 ,  A61P35/02 ,  C12N5/0695 ,  C12N15/1137 ,  C12Q1/6851 ,  C12Q1/686 ,  C12Q1/6886 ,  G01N33/57426 ,  C12N2330/51 ,  C12Q2600/158 ,  C12Q2600/178 ,  C12Y305/04

摘要： In alternative embodiment, provided are methods and compositions for treating, ameliorating or preventing diseases and conditions, such as cancer, including cancers associated with stem cells such as, without limitation, myelodysplastic syndrome (MDS) and a myeloproliferative neoplasm like chronic myeloid leukemia (CML) or acute myeloid leukemia (AML), and ablating or killing cancer stem cells. In alternative embodiment, provided are a new set of biomarkers to detect leukemia stem cell reprogramming and CML progression. In alternative embodiment, provided are therapeutic targets for treating myelodysplastic syndrome (MDS) and chronic myeloid leukemia (CML) by targeting edited let-7 transcripts.

公开(公告)号：US11976309B2

公开(公告)日：2024-05-07

申请号：US17839233

申请日：2022-06-13

申请人： The Regents of the University of California

发明人： Yuxuan Zheng ,  Claire Lorenzo ,  Peter Beal ,  Andrew Fisher ,  Leanna Monteleone

IPC分类号： C12N9/78 ,  A61K38/00 ,  C12N9/16 ,  C12N15/62

CPC分类号： C12N9/78 ,  C12N9/16 ,  C12N15/62 ,  A61K38/00 ,  C12Y305/04

摘要： In some aspects, the present invention provides methods and compositions for modifying target sites within nucleic acid molecules. In some embodiments, the methods comprise using adenosine deaminases that act on RNA (ADARs), and variants thereof, to modify target sites within DNA-RNA hybrid molecules. In other aspects, ADAR2 variant polypeptides as well as fusion proteins comprising an ADAR catalytic domain and a hybrid nucleic acid binding domain are provided, as are methods for use thereof. Methods for preventing and treating genetic disorders are also provided herein.

公开(公告)号：US20240011028A9

公开(公告)日：2024-01-11

申请号：US17920065

申请日：2021-04-22

申请人： Shape Therapeutics Inc.

发明人： Susan BYRNE

IPC分类号： C12N15/113 ,  C12N9/78 ,  C12N15/87

CPC分类号： C12N15/113 ,  C12N9/78 ,  C12Y305/04 ,  C12N15/87 ,  C12N2310/11 ,  C12N2310/531 ,  C12N2320/33

摘要： Disclosed herein are compositions, pharmaceutical compositions, and methods of use comprising an engineered polynucleotide that can be used to hybridize with a target RNA which may contain a nucleotide mismatch. Compositions and methods disclosed herein can be used to edit RNA to ameliorate or treat diseases or conditions in a subject.

公开(公告)号：US20230357838A1

公开(公告)日：2023-11-09

申请号：US18323143

申请日：2023-05-24

申请人： New England Biolabs, Inc.

发明人： Zhiyi Sun ,  Sean R. Johnson ,  Bo Yan ,  Lixin Chen ,  G. Brett Robb ,  Thomas C. Evans, JR. ,  Romualdas Vaisvila

IPC分类号： C12Q1/6869 ,  C12N9/02 ,  C12N9/10 ,  C12N9/78

CPC分类号： C12Q1/6869 ,  C12N9/0071 ,  C12Y114/11 ,  C12N9/1051 ,  C12Y204/01027 ,  C12N9/78 ,  C12Y305/04

摘要： Provided herein, among other things, is a method for deaminating a double-stranded nucleic acid. In some embodiments, the method may comprise contacting a double-stranded DNA substrate that comprises cytosines and a double-stranded DNA deaminase having an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 21, 40, 47, 49, 50, 55, 58, 59, 62, 63, 65, 67, 70, 71, 76, 106, 107, 110, 112, 114, 117, 163 and/or 164 to produce a deamination product that comprises deaminated cytosines. Enzymes and kits for performing the method are also provided.

公开(公告)号：US20170268022A1

公开(公告)日：2017-09-21

申请号：US15329925

申请日：2015-07-30

申请人： President and Fellows of Harvard College

发明人： David R. Liu ,  Kevin Davis

IPC分类号： C12N15/90 ,  C07K14/72 ,  C12N15/63 ,  C12N9/78 ,  C12N9/02 ,  C07K14/35 ,  C12N9/22

CPC分类号： C12N15/907 ,  C07K14/35 ,  C07K14/721 ,  C07K2319/92 ,  C12N9/0071 ,  C12N9/22 ,  C12N9/78 ,  C12N15/63 ,  C12P19/34 ,  C12Y114/11 ,  C12Y305/04

摘要： Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity of RNA-programmable endonucleases, such as Cas9, or for controlling the activity of proteins comprising a Cas9 variant fused to a functional effector domain, such as a nuclease, nickase, recombinase, deaminase, transcriptional activator, transcriptional repressor, or epigenetic modifying domain. For example, the inventive proteins provided comprise a ligand-dependent intein, the presence of which inhibits one or more activities of the protein (e.g., gRNA binding, enzymatic activity, target DNA binding). The binding of a ligand to the intein results in self-excision of the intein, restoring the activity of the protein.

公开(公告)号：US20150166981A1

公开(公告)日：2015-06-18

申请号：US14326109

申请日：2014-07-08

申请人： President and Fellows of Harvard College

发明人： David R. Liu ,  Alexis Christine Komor

IPC分类号： C12N15/01 ,  C12N9/78

CPC分类号： C12N9/22 ,  A61K38/465 ,  A61K38/50 ,  A61K47/61 ,  C07K2319/00 ,  C07K2319/80 ,  C12N9/6472 ,  C12N9/78 ,  C12N15/01 ,  C12N15/102 ,  C12P19/34 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Y301/00 ,  C12Y301/22 ,  C12Y304/22062 ,  C12Y305/04 ,  C12Y305/04001 ,  C12Y305/04004 ,  C12Y305/04005

摘要： 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 of Cas9 and nucleic acid editing enzymes or enzyme domains, e.g., deaminase domains, are provided. 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 Cas9 and nucleic acid editing enzymes or domains, are provided.

摘要翻译： 本公开的一些方面提供可用于靶向编辑核酸的策略，系统，试剂，方法和试剂盒，包括在细胞或受试者的基因组内例如编码人类基因组内的单个位点。 在一些实施方案中，提供Cas9的融合蛋白和核酸编辑酶或酶结构域，例如脱氨酶结构域。 在一些实施方案中，提供了靶向核酸编辑的方法。 在一些实施方案中，提供用于产生靶向核酸编辑蛋白（例如Cas9的融合蛋白）和核酸编辑酶或结构域的试剂和试剂盒。

公开(公告)号：US20240352465A1

公开(公告)日：2024-10-24

申请号：US18507935

申请日：2023-11-13

申请人： The Regents of the University of California

发明人： Prashant Mali ,  Dhruva Katrekar

IPC分类号： C12N15/115 ,  A61K38/00 ,  A61P21/00 ,  C12N9/78 ,  C12N15/113

CPC分类号： C12N15/115 ,  A61P21/00 ,  C12N9/78 ,  C12Y305/04 ,  A61K38/00 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/20 ,  C12N2310/531 ,  C12N2320/34

摘要： Aspects of the disclosure relate to a gene therapy approach for diseases, disorders, or conditions caused by mutation in the stop codon utilizing modified tRNA. At least 10-15% of all genetic diseases, including muscular dystrophy (e.g. Duchene muscular dystrophy), some cancers, beta thalassemia, Hurler syndrome, and cystic fibrosis, fall into this category. Not to be bound by theory, it is believed that this approach is safer than CRISPR approaches due to minimal off-target effects and the lack of genome level changes.

公开(公告)号：US20240309404A1

公开(公告)日：2024-09-19

申请号：US18653454

申请日：2024-05-02

申请人： Metagenomi, Inc.

发明人： Brian C. THOMAS ,  Jyun-Liang LIN ,  Alan BROOKS ,  Cristina BUTTERFIELD ,  Christopher BROWN ,  Cindy CASTELLE ,  Morayma TEMOCHE-DIAZ ,  Benjamin FREEMAN ,  Christine ROMANO ,  Rebecca LAMOTHE

IPC分类号： C12N15/90 ,  C12N9/22 ,  C12N9/78 ,  C12N15/11

CPC分类号： C12N15/90 ,  C12N9/22 ,  C12N9/78 ,  C12N15/11 ,  C12Y305/04 ,  C12Y305/04002 ,  C12Y305/04004 ,  C12Y305/04005 ,  C12N2310/20

摘要： The present disclosure provides for endonuclease enzymes having distinguishing domain features, as well as methods of using such enzymes or variants thereof.

公开(公告)号：US20240254516A1

公开(公告)日：2024-08-01

申请号：US18634640

申请日：2024-04-12

申请人： National University Corporation Kobe University

发明人： Keiji NISHIDA

IPC分类号： C12N15/90 ,  C12N9/22 ,  C12N9/78 ,  C12N15/11

CPC分类号： C12N15/907 ,  C12N9/22 ,  C12N9/78 ,  C12N15/11 ,  C12N15/90 ,  C12Y305/04 ,  C12N2310/20 ,  C12N2800/80

摘要： The present invention provides a complex containing a nucleic acid sequence-recognizing module and a proteolysis tag, wherein the module is linked to the proteolysis tag, the module specifically binds to a target nucleotide sequence in a double stranded DNA, and the tag consists of (i) a peptide containing 3 hydrophobic amino acid residues at the C-terminal, or (ii) a peptide containing 3 amino acid residues at the C-terminal wherein at least a part of the amino acid residues is substituted by serine

公开(公告)号：US11898179B2

公开(公告)日：2024-02-13

申请号：US16492548

申请日：2018-03-09

申请人： President and Fellows of Harvard College

发明人： Juan Pablo Maianti ,  David R. Liu

IPC分类号： C12N9/78 ,  A61K9/00 ,  A61K31/7088 ,  A61K38/46 ,  C12N9/22 ,  C12N9/96 ,  A61K48/00 ,  C12N15/11 ,  A61K38/50

CPC分类号： C12N9/78 ,  A61K9/0029 ,  A61K9/0053 ,  A61K31/7088 ,  A61K38/465 ,  A61K38/50 ,  C12N9/22 ,  C12N9/96 ,  C12N15/11 ,  C12Y305/04 ,  A61K48/00 ,  C07K2319/00 ,  C12N2310/20 ,  C12N2320/31 ,  C12N2320/32 ,  C12N2800/80

摘要： Provided herein are systems, compositions, kits, and methods for the suppression of pain (e.g., chronic pain). Genes encoding ion channels (e.g., SCN9A) responsible for the propagation pain signals in neurons (e.g., DRG neurons) may be edited using a genome editing agent (e.g., a nucleobase editor). In some embodiments, loss-of-function ion channel mutants are generated, leading to pain suppression. In some embodiments, the genome editing agent is administered locally to the site of pain or to the nerves responsible for propagation of the pain signal.