CA3047429A1 - Hsd17b13 variants and uses thereof - Google Patents

Hsd17b13 variants and uses thereof Download PDF

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Publication number
CA3047429A1
CA3047429A1 CA3047429A CA3047429A CA3047429A1 CA 3047429 A1 CA3047429 A1 CA 3047429A1 CA 3047429 A CA3047429 A CA 3047429A CA 3047429 A CA3047429 A CA 3047429A CA 3047429 A1 CA3047429 A1 CA 3047429A1
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Prior art keywords
seq
gene
guide rna
hsd17b13
cell
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CA3047429A
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English (en)
French (fr)
Inventor
Noura S. ABUL-HUSN
Omri GOTTESMAN
Alexander LI
Xiping CHENG
Yurong XIN
Evangelos PEFANIS
Suzanne HARTFORD
Jesper Gromada
Frederick E. DEWEY
Aris BARAS
Alan Shuldiner
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Regeneron Pharmaceuticals Inc
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Regeneron Pharmaceuticals Inc
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Publication of CA3047429A1 publication Critical patent/CA3047429A1/en
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Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2019126483A (ru) 2017-01-23 2021-02-24 Ридженерон Фармасьютикалз, Инк. Варианты 17-бета-гидроксистероиддегидрогеназы 13 (hsd17b13) и их применение
KR20190139869A (ko) 2017-04-11 2019-12-18 리제너론 파마슈티칼스 인코포레이티드 하이드록시스테로이드 (17-베타) 탈수소효소(hsd17b) 패밀리의 구성원의 조절인자의 활성도를 스크리닝하기 위한 검정
AU2018348195B2 (en) 2017-10-11 2025-05-15 Regeneron Pharmaceuticals, Inc. Inhibition of HSD17B13 in the treatment of liver disease in patients expressing the PNPLA3 I148M variation
US20210000906A1 (en) * 2018-03-21 2021-01-07 Ionis Pharmaceuticals, Inc. Modulation of hsd17b13 expression
AU2019239971B2 (en) * 2018-03-21 2025-09-11 Regeneron Pharmaceuticals, Inc. 17beta-hydroxysteroid dehydrogenase type 13 (HSD17b13) iRNA compositions and methods of use thereof
KR102922694B1 (ko) 2018-04-19 2026-02-03 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 유전자 편집을 위한 조성물 및 방법
KR102769565B1 (ko) * 2018-09-19 2025-02-20 애로우헤드 파마슈티컬스 인코포레이티드 17베타-HSD 유형 13- (HSD17B13)의 발현을 억제하기 위한 RNAi 작용제, 그의 조성물, 및 사용 방법
CR20210395A (es) * 2018-12-21 2021-11-05 Ionis Pharmaceuticals Inc Moduladores de la expresión de hsd17b13
US11957687B2 (en) 2019-07-02 2024-04-16 Regeneron Pharmaceuticals, Inc. Modulators of HSD17B13 and methods of use thereof
KR20230004456A (ko) * 2020-03-04 2023-01-06 리제너론 파아마슈티컬스, 인크. 면역 요법에 대한 종양 세포의 감작화를 위한 방법 및 조성물
KR20240004092A (ko) * 2020-06-01 2024-01-11 암젠 인크 Hsd17b13 발현을 억제하기 위한 rnai 작제물 및 이의 사용 방법
US20230416802A1 (en) * 2020-11-06 2023-12-28 Inipharm, Inc. Specific substrates and products of hsd17b13 as markers of liver disease and biomarkers for liver disease treatment
CN112626199A (zh) * 2021-01-04 2021-04-09 杭州艾迪康医学检验中心有限公司 检测慢性肝炎转化为肝硬化的风险预测位点的引物和方法
CA3216332A1 (en) * 2021-04-22 2022-10-27 Tuojie Biotech (Shanghai) Co., Ltd. Sirna targeting 17b-hydroxysteroid dehydrogenase type 13 and sirna conjugate
CN118103038A (zh) 2021-08-20 2024-05-28 英安塔制药有限公司 17β-羟基类固醇脱氢酶13型抑制剂及其使用方法
EP4433596A4 (en) * 2021-11-19 2026-02-11 Wave Life Sciences Ltd DOUBLE-STRANDED OLIGONUCLETIC COMPOSITIONS ASSOCIATED WITH HSD17B13 AND RELATED PROCESSES
WO2024131916A1 (en) * 2022-12-22 2024-06-27 Shanghai Argo Biopharmaceutical Co., Ltd. Compositions and methods for inhibiting expression of 17beta-hydroxysteroid dehydrogenase type 13 (hsd17b13)
WO2024173343A1 (en) 2023-02-14 2024-08-22 Regeneron Pharmaceuticals, Inc. Compounds targeting hydroxysteroid 17-beta dehydrogenase (hsd17b) and uses thereof
WO2025153088A1 (zh) * 2024-01-18 2025-07-24 北京安龙生物医药有限公司 靶向第13型17β-羟基类固醇脱氢酶的寡核苷酸及其用途
WO2025162435A1 (en) * 2024-02-02 2025-08-07 Accuredit Therapeutics (Suzhou) Co., Ltd. Compositions and methods for treatment of liver disease
TW202540424A (zh) * 2024-02-03 2025-10-16 大陸商北京福元醫藥股份有限公司 用於抑制HSD17B13表達的siRNA、其綴合物和藥物組合物及其用途

Family Cites Families (315)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4209A (en) * 1845-09-27 Straw-cutter
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US5179017A (en) 1980-02-25 1993-01-12 The Trustees Of Columbia University In The City Of New York Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4399216A (en) 1980-02-25 1983-08-16 The Trustees Of Columbia University Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4634665A (en) 1980-02-25 1987-01-06 The Trustees Of Columbia University In The City Of New York Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
US4510245A (en) 1982-11-18 1985-04-09 Chiron Corporation Adenovirus promoter system
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5168062A (en) 1985-01-30 1992-12-01 University Of Iowa Research Foundation Transfer vectors and microorganisms containing human cytomegalovirus immediate-early promoter-regulatory DNA sequence
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US4751180A (en) 1985-03-28 1988-06-14 Chiron Corporation Expression using fused genes providing for protein product
US4683202A (en) * 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
US4935233A (en) 1985-12-02 1990-06-19 G. D. Searle And Company Covalently linked polypeptide cell modulators
US4968615A (en) 1985-12-18 1990-11-06 Ciba-Geigy Corporation Deoxyribonucleic acid segment from a virus
US4800159A (en) 1986-02-07 1989-01-24 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
EP0366685B1 (en) 1987-06-24 1994-10-19 Howard Florey Institute Of Experimental Physiology And Medicine Nucleoside derivatives
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
JPH03503894A (ja) 1988-03-25 1991-08-29 ユニバーシィティ　オブ　バージニア　アランミ　パテンツ　ファウンデイション オリゴヌクレオチド　ｎ‐アルキルホスホラミデート
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5294533A (en) 1988-07-05 1994-03-15 Baylor College Of Medicine Antisense oligonucleotide antibiotics complementary to the macromolecular synthesis operon, methods of treating bacterial infections and methods for identification of bacteria
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
DE69034150T2 (de) 1989-10-24 2005-08-25 Isis Pharmaceuticals, Inc., Carlsbad 2'-Modifizierte Oligonukleotide
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
AU7579991A (en) 1990-02-20 1991-09-18 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
ES2116977T3 (es) 1990-05-11 1998-08-01 Microprobe Corp Soportes solidos para ensayos de hibridacion de acidos nucleicos y metodos para inmovilizar oligonucleotidos de modo covalente.
US5135917A (en) 1990-07-12 1992-08-04 Nova Pharmaceutical Corporation Interleukin receptor expression inhibiting antisense oligonucleotides
JPH0874B2 (ja) 1990-07-27 1996-01-10 アイシス・ファーマシューティカルス・インコーポレーテッド 遺伝子発現を検出および変調するヌクレアーゼ耐性、ピリミジン修飾オリゴヌクレオチド
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
MY107332A (en) 1990-08-03 1995-11-30 Sterling Drug Inc Compounds and methods for inhibiting gene expression.
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
JPH06505704A (ja) 1990-09-20 1994-06-30 ギリアド　サイエンシズ，インコーポレイテッド 改変ヌクレオシド間結合
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
US5271941A (en) 1990-11-02 1993-12-21 Cho Chung Yoon S Antisense oligonucleotides of human regulatory subunit RI.sub.α of cAMP-dependent protein kinases
KR930702373A (ko) 1990-11-08 1993-09-08 안토니 제이. 페이네 합성 올리고누클레오티드에 대한 다중 리포터(Reporter)그룹의 첨합
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
EP0538194B1 (de) 1991-10-17 1997-06-04 Novartis AG Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
US5786138A (en) 1993-01-29 1998-07-28 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Hyperstabilizing antisense nucleic acid binding agents
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
CA2159631A1 (en) 1993-03-30 1994-10-13 Sanofi Acyclic nucleoside analogs and oligonucleotide sequences containing them
HU9501974D0 (en) 1993-03-31 1995-09-28 Sterling Winthrop Inc Oligonucleotides with amide linkages replacing phosphodiester linkages
DE4311944A1 (de) 1993-04-10 1994-10-13 Degussa Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen
CA2164288A1 (en) 1993-06-04 1994-12-22 Barbara Ensoli Method for treating kaposi's sarcoma with antisense oligonucleotides
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5578716A (en) 1993-12-01 1996-11-26 Mcgill University DNA methyltransferase antisense oligonucleotides
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5641754A (en) 1994-01-10 1997-06-24 The Board Of Regents Of The University Of Nebraska Antisense oligonucleotide compositions for selectively killing cancer cells
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5624813A (en) 1994-04-21 1997-04-29 Mahant; Vijay K. NAD(P)+ /NAD(P)H based chemiluminescent diagnostics
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
EP0775204A1 (en) 1994-08-09 1997-05-28 Novartis AG Antitumor antisense oligonucleotides
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5856103A (en) 1994-10-07 1999-01-05 Board Of Regents The University Of Texas Method for selectively ranking sequences for antisense targeting
US5994320A (en) 1995-02-06 1999-11-30 Regents Of The University Of Minnesota Antisense oligonucleotides and methods for treating central nervous system tumors
IT1275862B1 (it) 1995-03-03 1997-10-24 Consiglio Nazionale Ricerche Trascritto antisenso associato ad alcuni tipi di cellule tumorali ed oligodeossinucleotidi sintetici utili nella diagnosi e nel trattamento
US6040296A (en) 1995-06-07 2000-03-21 East Carolina University Specific antisense oligonucleotide composition & method for treatment of disorders associated with bronchoconstriction and lung inflammation
FR2739029B1 (fr) 1995-09-21 1997-11-21 Roussel Uclaf Nouvelle application therapeutique des composes antimineralo-corticoides
AU7286696A (en) 1995-10-13 1997-05-07 F. Hoffmann-La Roche Ag Antisense oligomers
CZ154898A3 (cs) 1995-11-21 1998-09-16 Icn Pharmaceuticals, Inc. Oligonukleotidy pro inhibici růstu nádorů zprostředkovaných IL-8 a receptorem IL-8
WO1997020942A1 (en) 1995-12-05 1997-06-12 Piao Yun Shang Hsd17b1 promoter, enhancer, silencer and use thereof
CN1215994A (zh) 1996-02-15 1999-05-05 国家健康学会 对治疗rsv感染有效的rna酶l激活剂和反义寡核苷酸
US5955590A (en) 1996-07-15 1999-09-21 Worcester Foundation For Biomedical Research Conjugates of minor groove DNA binders with antisense oligonucleotides
US6046004A (en) 1997-02-27 2000-04-04 Lorne Park Research, Inc. Solution hybridization of nucleic acids with antisense probes having modified backbones
JPH1142091A (ja) 1997-07-25 1999-02-16 Toagosei Co Ltd アンチセンス核酸化合物
US6391311B1 (en) 1998-03-17 2002-05-21 Genentech, Inc. Polypeptides having homology to vascular endothelial cell growth factor and bone morphogenetic protein 1
CA2248762A1 (en) 1997-10-22 1999-04-22 University Technologies International, Inc. Antisense oligodeoxynucleotides regulating expression of tnf-.alpha.
ES2312205T3 (es) 1998-03-10 2009-02-16 Genentech, Inc. Nuevo polipeptido y acidos nucleicos que lo codifican.
HUP0101809A3 (en) 1998-03-11 2002-07-29 Endorech Inc Sainte Foy Inhibitors of type 5 and type 3 17betha-hydroxysteroid dehydrogenase and methods for their use
US6007995A (en) 1998-06-26 1999-12-28 Isis Pharmaceuticals Inc. Antisense inhibition of TNFR1 expression
US6599692B1 (en) 1999-09-14 2003-07-29 Sangamo Bioscience, Inc. Functional genomics using zinc finger proteins
US6013522A (en) 1999-02-23 2000-01-11 Isis Pharmaceuticals Inc. Antisense inhibition of human Smad1 expression
US20030104526A1 (en) 1999-03-24 2003-06-05 Qiang Liu Position dependent recognition of GNN nucleotide triplets by zinc fingers
US6025198A (en) 1999-06-25 2000-02-15 Isis Pharmaceuticals Inc. Antisense modulation of Ship-2 expression
US6033910A (en) 1999-07-19 2000-03-07 Isis Pharmaceuticals Inc. Antisense inhibition of MAP kinase kinase 6 expression
FR2801218B1 (fr) 1999-11-23 2001-12-28 Hoechst Marion Roussel Inc Compositions pharmaceutiques comprenant de la trimegestone, leurs procedes de preparation ainsi que le conditionnement primaire les renfermant
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
AU2002228841C1 (en) 2000-12-07 2006-11-23 Sangamo Biosciences, Inc Regulation of angiogenesis with zinc finger proteins
WO2002057293A2 (en) 2001-01-22 2002-07-25 Sangamo Biosciences, Inc. Modified zinc finger binding proteins
AU2002225187A1 (en) 2001-01-22 2002-07-30 Sangamo Biosciences, Inc. Zinc finger polypeptides and their use
WO2003087341A2 (en) 2002-01-23 2003-10-23 The University Of Utah Research Foundation Targeted chromosomal mutagenesis using zinc finger nucleases
WO2003080809A2 (en) 2002-03-21 2003-10-02 Sangamo Biosciences, Inc. Methods and compositions for using zinc finger endonucleases to enhance homologous recombination
EP2806025B1 (en) 2002-09-05 2019-04-03 California Institute of Technology Use of zinc finger nucleases to stimulate gene targeting
US7754709B2 (en) 2003-06-10 2010-07-13 Solvay Pharmaceuticals Bv Tetracyclic thiophenepyrimidinone compounds as inhibitors of 17β hydroxysteroid dehydrogenase compounds
US8409861B2 (en) 2003-08-08 2013-04-02 Sangamo Biosciences, Inc. Targeted deletion of cellular DNA sequences
US7888121B2 (en) 2003-08-08 2011-02-15 Sangamo Biosciences, Inc. Methods and compositions for targeted cleavage and recombination
US20050158376A1 (en) 2003-10-23 2005-07-21 Sardi William F. Dietary supplement and method of processing same
US20090169585A1 (en) 2003-10-23 2009-07-02 Resveratrol Partners, Llc Resveratrol-Containing Compositions And Their Use In Modulating Gene Product Concentration Or Activity
US20080299042A1 (en) 2004-04-30 2008-12-04 Biogen Idec Ma Inc. Membrane Associated Molecules
US7820380B2 (en) 2004-05-07 2010-10-26 Celera Corporation Genetic polymorphisms associated with liver fibrosis
AU2005287278B2 (en) 2004-09-16 2011-08-04 Sangamo Biosciences, Inc. Compositions and methods for protein production
FR2904000A1 (fr) 2006-07-19 2008-01-25 Galderma Res & Dev S N C Snc Modulateurs de hsd17b7 dans le traitement de l'acne ou de l'hyperseborrhee
US20090203602A1 (en) 2006-09-01 2009-08-13 Cohava Gelber Compositions and methods for diagnosis and treatment of type 2 diabetes
US20100267052A1 (en) 2006-09-01 2010-10-21 American Type Culture Collection Compositions and methods for diagnosis and treatment of type 2 diabetes
US7951776B2 (en) 2006-09-01 2011-05-31 American Type Culture Collection Methods for treatment of type 1 diabetes
US20080300170A1 (en) 2006-09-01 2008-12-04 Cohava Gelber Compositions and methods for diagnosis and treatment for type 2 diabetes
WO2008091873A2 (en) 2007-01-24 2008-07-31 Dana-Farber Cancer Institute, Inc. Compositions and methods for the identification, assessment, prevention and therapy of thymic lymphoma or hamartomatous tumours
ES2586210T3 (es) 2006-12-14 2016-10-13 Sangamo Biosciences, Inc. Proteínas de dedo de zinc no canónicas optimizadas
JP2010540444A (ja) 2007-09-20 2010-12-24 レスベラトロル パートナーズ， エルエルシー 遺伝子産物の濃縮または活性を調節するためのレスベラトロールを含む組成物
JP2011517838A (ja) 2008-04-11 2011-06-16 ユーティーシー パワー コーポレイション マニホルド・サンプを備えたバイポーラプレートおよび燃料電池
EP2298359A1 (en) 2008-06-04 2011-03-23 Kyowa Hakko Kirin Co., Ltd. Nucleic acid capable of controlling degranulation of mast cell
WO2010028110A2 (en) * 2008-09-04 2010-03-11 Board Of Regents, The University Of Texas System Sequence variations in pnpla3 associated with hepatic steatosis
US20100209427A1 (en) 2008-09-24 2010-08-19 Yu Li Lysine acetylation sites
EP2177615A1 (en) 2008-10-10 2010-04-21 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Method for a genome wide identification of expression regulatory sequences and use of genes and molecules derived thereof for the diagnosis and therapy of metabolic and/or tumorous diseases
JPWO2010064702A1 (ja) 2008-12-05 2012-05-10 国立大学法人 東京大学 癌の予後を予測するためのバイオマーカー
EP2206723A1 (en) 2009-01-12 2010-07-14 Bonas, Ulla Modular DNA-binding domains
US20110239315A1 (en) 2009-01-12 2011-09-29 Ulla Bonas Modular dna-binding domains and methods of use
CA2697169A1 (en) 2009-03-18 2010-09-18 David Stojdl Compositions and methods for augmenting activity of oncolytic viruses
EP2408921B1 (en) 2009-03-20 2017-04-19 Sangamo BioSciences, Inc. Modification of cxcr4 using engineered zinc finger proteins
WO2010120526A2 (en) 2009-03-31 2010-10-21 Emory University Methods and systems for screening for and diagnosing dna methylation associated with autism spectrum disorders
US8772008B2 (en) 2009-05-18 2014-07-08 Sangamo Biosciences, Inc. Methods and compositions for increasing nuclease activity
US9051567B2 (en) 2009-06-15 2015-06-09 Tekmira Pharmaceuticals Corporation Methods for increasing efficacy of lipid formulated siRNA
ES2657737T3 (es) 2009-07-15 2018-03-06 Calimmune Inc. Vector dual para la inhibición del virus de la inmunodeficiencia humana
WO2011006214A1 (en) 2009-07-16 2011-01-20 Peter Maccallum Cancer Institute Method of detecting radiation exposure and adverse toxicity thereto
WO2011017293A2 (en) 2009-08-03 2011-02-10 The General Hospital Corporation Engineering of zinc finger arrays by context-dependent assembly
US8518392B2 (en) 2009-08-14 2013-08-27 Regeneron Pharmaceuticals, Inc. Promoter-regulated differentiation-dependent self-deleting cassette
CA2779858C (en) 2009-10-29 2019-10-29 Regeneron Pharmaceuticals, Inc. Multifunctional alleles
CA2781654A1 (en) 2009-11-25 2011-06-03 Hua Gong Novel genomic biomarkers for irritable bowel syndrome diagnosis
WO2011072246A2 (en) 2009-12-10 2011-06-16 Regents Of The University Of Minnesota Tal effector-mediated dna modification
WO2011084747A2 (en) 2009-12-21 2011-07-14 The Johns Hopkins University Compositions and methods for somatic tissue induced pluripotent stem cells having an endoderm origin
US20130029873A1 (en) 2010-04-12 2013-01-31 University Health Network Methods and compositions for diagnosing pulmonary fibrosis subtypes and assessing the risk of primary graft dysfunction after lung transplantation
WO2011128096A1 (en) 2010-04-16 2011-10-20 Roche Diagnostics Gmbh Polymorphism markers for predicting response to interleukin-6 receptor-inhibiting monoclonal antibody drug treatment
DK2569446T3 (en) 2010-05-12 2018-10-29 Steven E Schutzer DIAGNOSTIC MARKERS FOR NEUROPsychiatric Disease
WO2011145121A1 (en) 2010-05-18 2011-11-24 Scatolificio Mogliani S.N.C. Di Mogliani Mauro E Andrea Cardboard box for stable stacking with other identical specimens
US8945847B2 (en) 2010-05-24 2015-02-03 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Methods and kits for ascertaining biosafety of an agent
US20120058088A1 (en) 2010-06-28 2012-03-08 Resveratrol Partners, Llc Resveratrol-Containing Compositions And Methods Of Use
CA2804763C (en) 2010-07-14 2023-01-03 The Regents Of The University Of California Biomarkers for diagnosis of transient ischemic attacks
WO2012031008A2 (en) 2010-08-31 2012-03-08 The General Hospital Corporation Cancer-related biological materials in microvesicles
WO2012052953A1 (en) 2010-10-20 2012-04-26 Fondazione Centro San Raffaele Del Monte Tabor MiRNA
WO2012058097A1 (en) 2010-10-26 2012-05-03 Buck Institute For Age Research Downregulation of sine/alu retrotransposon transcription to induce or restore proliferative capacity and/or pluripotency to a stem cell
US9920317B2 (en) 2010-11-12 2018-03-20 The General Hospital Corporation Polycomb-associated non-coding RNAs
CA2817256A1 (en) 2010-11-12 2012-05-18 The General Hospital Corporation Polycomb-associated non-coding rnas
WO2012070014A2 (en) 2010-11-26 2012-05-31 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Identification of novel cell surface markers for pancreatic progenitor cells and definite endodermal cells
US20140057800A1 (en) 2010-12-16 2014-02-27 Norwegian Univeristy of Science and Technology (NTNU) Single nucleotide polymorphism associated with risk of insulin resistance development
EP2655621B1 (en) 2010-12-20 2018-05-23 The General Hospital Corporation Polycomb-associated non-coding rnas
WO2012151346A1 (en) 2011-05-03 2012-11-08 Dermachip Inc. Expression signatures of genes and gene networks associated with skin aging
GB201112246D0 (en) 2011-07-15 2011-08-31 Univ Birmingham Diagnosis of alzheimer's disease
US20130079241A1 (en) 2011-09-15 2013-03-28 Jianhua Luo Methods for Diagnosing Prostate Cancer and Predicting Prostate Cancer Relapse
WO2013126565A1 (en) 2012-02-24 2013-08-29 Lunyak Victoria V Downregulation of sine/alu retrotransposon transcription to induce or restore proliferative capacity and/or pluripotency to a stem cell
US9637739B2 (en) 2012-03-20 2017-05-02 Vilnius University RNA-directed DNA cleavage by the Cas9-crRNA complex
WO2013141680A1 (en) 2012-03-20 2013-09-26 Vilnius University RNA-DIRECTED DNA CLEAVAGE BY THE Cas9-crRNA COMPLEX
WO2013166264A2 (en) 2012-05-02 2013-11-07 University Of Georgia Research Foundation, Inc. Methods for altering virus replication
US9677138B2 (en) 2012-05-20 2017-06-13 Trustees Of Boston University Methods and systems for monitoring, diagnosing, and treating chronic obstructive pulmonary disease
AU2013266968B2 (en) 2012-05-25 2017-06-29 Emmanuelle CHARPENTIER Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription
EP2864791A2 (en) 2012-06-20 2015-04-29 Leibniz - Institut für Analytische Wissenschaften - ISAS - E.V. Specific biomarkers for hepatocellular carcinoma (hcc)
US20140004153A1 (en) 2012-07-02 2014-01-02 Lancell, L.L.C. Use of somatic mutations in the extracellular domain of transmembrane proteins in a patient's tumor as immunogens for active humoral immunotherapy of cancer
WO2014028946A2 (en) 2012-08-17 2014-02-20 The Broad Institute, Inc. Modulators of hepatic lipoprotein metabolism
WO2014033644A2 (en) 2012-08-28 2014-03-06 Novartis Ag Methods of nuclease-based genetic engineering
US9375433B2 (en) 2012-09-26 2016-06-28 Tangent Reprofiling Limited Modulators of androgen synthesis
NZ706067A (en) 2012-09-26 2016-07-29 Tangent Reprofiling Ltd Modulators of androgen synthesis
AU2013335451C1 (en) 2012-10-23 2024-07-04 Toolgen Incorporated Composition for cleaving a target DNA comprising a guide RNA specific for the target DNA and Cas protein-encoding nucleic acid or Cas protein, and use thereof
IL292159B1 (en) 2012-12-05 2026-04-01 Alnylam Pharmaceuticals Inc PCSK9 iRNA compositions and methods of using them
PL3360964T3 (pl) 2012-12-06 2020-03-31 Sigma-Aldrich Co. Llc Modyfikacja i regulacja genomu oparta na crispr
EP4331620A3 (en) 2012-12-07 2024-12-04 Translate Bio, Inc. Lipidic nanoparticles for mrna delivery
US20140186843A1 (en) 2012-12-12 2014-07-03 Massachusetts Institute Of Technology Methods, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
EP3031921B1 (en) 2012-12-12 2025-03-12 The Broad Institute, Inc. Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
DK2931891T3 (da) 2012-12-17 2019-08-19 Harvard College Rna-styret modificering af menneskelige genomer
MX384291B (es) 2013-02-20 2025-03-14 Regeneron Pharma Modificación genética de ratas.
EP2922393B2 (en) 2013-02-27 2022-12-28 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Gene editing in the oocyte by cas9 nucleases
EP2970940B1 (en) 2013-03-14 2018-07-25 Translate Bio, Inc. Mrna therapeutic compositions and use to treat diseases and disorders
US20160032395A1 (en) 2013-03-14 2016-02-04 Elai Davicioni Cancer biomarkers and classifiers and uses thereof
EP2968988A4 (en) * 2013-03-14 2016-11-16 Allegro Diagnostics Corp METHOD FOR EVALUATING A COPD STATUS
CN105247075B (zh) 2013-03-15 2019-02-15 威拉赛特公司 用于诊断肺病的生物标记物及其使用方法
CN112301024A (zh) 2013-03-15 2021-02-02 通用医疗公司 使用RNA引导的FokI核酸酶(RFN)提高RNA引导的基因组编辑的特异性
US20140329704A1 (en) 2013-03-28 2014-11-06 President And Fellows Of Harvard College Markers for mature beta-cells and methods of using the same
EP4286517A3 (en) 2013-04-04 2024-03-13 President and Fellows of Harvard College Therapeutic uses of genome editing with crispr/cas systems
GB201306536D0 (en) 2013-04-10 2013-05-22 Gt Biolog Ltd Polypeptide and immune modulation
EP2994531B1 (en) 2013-05-10 2018-03-28 Sangamo Therapeutics, Inc. Delivery methods and compositions for nuclease-mediated genome engineering
US9574241B2 (en) 2013-06-03 2017-02-21 The Trustees Of Columbia University In The City Of New York Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T-cell lymphomas
WO2014196957A1 (en) 2013-06-03 2014-12-11 Nestec Sa Methods for diagnosing chronic valvular disease
US9267135B2 (en) 2013-06-04 2016-02-23 President And Fellows Of Harvard College RNA-guided transcriptional regulation
RU2716420C2 (ru) 2013-06-17 2020-03-11 Те Брод Инститьют Инк. Доставка и применение систем crispr-cas, векторов и композиций для целенаправленного воздействия и терапии в печени
CN105683379A (zh) 2013-06-17 2016-06-15 布罗德研究所有限公司 用于对有丝分裂后细胞的疾病和障碍进行靶向和建模的系统、方法和组合物的递送、工程化和优化
US20150079062A1 (en) 2013-07-12 2015-03-19 Patrick J. Casey Method for harvesting, processing, and storage of proteins from the mammalian feto-placental unit and use of such proteins in compositions and medical treatment
EP3019186A4 (en) 2013-07-12 2017-03-29 Patrick J. Casey Method for the harvesting, processing, and storage of proteins from the mammalian feto-placental unit and use of such proteins in compositions and medical treatment
RU2545990C2 (ru) 2013-07-16 2015-04-10 Государственное бюджетное учреждение здравоохранения города Москвы Московский клинический научно-практический центр Департамента здравоохранения города Москвы Способ дифференциальной диагностики стеатоза печени и стеатогепатита
EP3441468B1 (en) 2013-10-17 2021-05-19 Sangamo Therapeutics, Inc. Delivery methods and compositions for nuclease-mediated genome engineering
ES3032935T3 (en) 2013-10-22 2025-07-29 Translate Bio Inc Lipid formulations for delivery of messenger rna
CN103520724B (zh) 2013-10-23 2016-05-25 江苏美迪森生物医药有限公司 Hsd17b13蛋白或其编码基因的抑制剂的新用途
GB201320061D0 (en) 2013-11-13 2013-12-25 Electrophoretics Ltd Materials nad methods for diagnosis and prognosis of liver cancer
WO2015127439A1 (en) 2014-02-24 2015-08-27 Sangamo Biosciences, Inc. Methods and compositions for nuclease-mediated targeted integration
WO2015169971A1 (en) 2014-05-09 2015-11-12 Tangent Reprofiling Limited Modulators of androgen synthesis
EP3155116A4 (en) 2014-06-10 2017-12-27 Massachusetts Institute Of Technology Method for gene editing
ES2788426T3 (es) 2014-06-16 2020-10-21 Univ Johns Hopkins Composiciones y métodos para la expresión de ARNs de guía de CRISPR utilizando el promotor de H1
US10588980B2 (en) 2014-06-23 2020-03-17 Novartis Ag Fatty acids and their use in conjugation to biomolecules
US20150376586A1 (en) 2014-06-25 2015-12-31 Caribou Biosciences, Inc. RNA Modification to Engineer Cas9 Activity
WO2016004387A1 (en) 2014-07-02 2016-01-07 H. Lee Moffitt Cancer Center And Research Institute, Inc. Gene expression signature for cancer prognosis
WO2016009246A1 (en) 2014-07-14 2016-01-21 Casey Patrick J Method for the harvesting, processing, and storage of proteins from the mammalian feto-placental unit and use of such proteins in compositions and medical treatment
WO2016028638A1 (en) 2014-08-18 2016-02-25 Drexel University Methods, computer-readable media, and systems for assessing samples and wounds, predicting whether a wound will heal, and monitoring effectiveness of a treatment
US20170335396A1 (en) 2014-11-05 2017-11-23 Veracyte, Inc. Systems and methods of diagnosing idiopathic pulmonary fibrosis on transbronchial biopsies using machine learning and high dimensional transcriptional data
CA2976445A1 (en) 2015-02-13 2016-08-18 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
CN104698108B (zh) 2015-03-26 2016-11-09 中国药科大学 一种利用固定化酶筛选I型17β羟类固醇脱氢酶抑制剂的方法
WO2017048620A1 (en) 2015-09-14 2017-03-23 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting patatin-like phospholipase domain containing 3 (pnpla3) and methods of use thereof
EP3159407A1 (en) 2015-10-23 2017-04-26 Silence Therapeutics (London) Ltd Guide rnas, methods and uses
EP3387129A1 (en) 2015-12-10 2018-10-17 Alnylam Pharmaceuticals, Inc. STEROL REGULATORY ELEMENT BINDING PROTEIN (SREBP) CHAPERONE (SCAP) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EP3390666A4 (en) 2015-12-14 2019-08-07 Cold Spring Harbor Laboratory COMPOSITIONS AND METHODS OF TREATING NURSE DISEASES
ES2903394T3 (es) 2015-12-14 2022-04-01 Cold Spring Harbor Laboratory Composiciones para el tratamiento de la retinitis pigmentosa 13
JP7036723B2 (ja) 2015-12-14 2022-03-15 コールド スプリング ハーバー ラボラトリー 眼疾患の処置のための組成物および方法
CA3005245A1 (en) 2015-12-14 2017-06-22 Cold Spring Harbor Laboratory Antisense oligomers for treatment of alagille syndrome
JP2019500345A (ja) 2015-12-14 2019-01-10 コールド スプリング ハーバー ラボラトリー 肝臓病の処置のための組成物および方法
EP3390635A4 (en) 2015-12-14 2019-05-01 Cold Spring Harbor Laboratory Antisense oligomers for the treatment of a tuberous sclerosis complex
JP7049249B2 (ja) 2015-12-14 2022-04-06 コールド スプリング ハーバー ラボラトリー 中枢神経系疾患の処置のための組成物および方法
US20190071795A1 (en) 2016-03-09 2019-03-07 Molecular Stethoscope, Inc. Methods and systems for detecting tissue conditions
CA3221950A1 (en) 2016-03-16 2017-09-21 Spogen Biotech Inc. Methods for promoting plant health using free enzymes and microorganisms that overexpress enzymes
WO2017191274A2 (en) 2016-05-04 2017-11-09 Curevac Ag Rna encoding a therapeutic protein
US10036024B2 (en) 2016-06-03 2018-07-31 Purdue Research Foundation siRNA compositions that specifically downregulate expression of a variant of the PNPLA3 gene and methods of use thereof for treating a chronic liver disease or alcoholic liver disease (ALD)
GB201609977D0 (en) 2016-06-08 2016-07-20 Cancer Rec Tech Ltd Chemosensitivity predictive biomarkers
US10767175B2 (en) 2016-06-08 2020-09-08 Agilent Technologies, Inc. High specificity genome editing using chemically modified guide RNAs
SG10202106058WA (en) 2016-12-08 2021-07-29 Intellia Therapeutics Inc Modified guide rnas
AU2017374042C1 (en) 2016-12-09 2024-07-11 Acuitas Therapeutics, Inc. Delivery of target specific nucleases
AU2017378427A1 (en) 2016-12-14 2019-06-20 Ligandal, Inc. Methods and compositions for nucleic acid and protein payload delivery
RU2019126483A (ru) 2017-01-23 2021-02-24 Ридженерон Фармасьютикалз, Инк. Варианты 17-бета-гидроксистероиддегидрогеназы 13 (hsd17b13) и их применение
CN118581154A (zh) 2017-06-02 2024-09-03 国家健康与医学研究院 用于遗传障碍的基因疗法的基因组编辑手段和结合病毒载体的基因疗法
AU2018348195B2 (en) 2017-10-11 2025-05-15 Regeneron Pharmaceuticals, Inc. Inhibition of HSD17B13 in the treatment of liver disease in patients expressing the PNPLA3 I148M variation
AU2019239971B2 (en) 2018-03-21 2025-09-11 Regeneron Pharmaceuticals, Inc. 17beta-hydroxysteroid dehydrogenase type 13 (HSD17b13) iRNA compositions and methods of use thereof
US20210000906A1 (en) 2018-03-21 2021-01-07 Ionis Pharmaceuticals, Inc. Modulation of hsd17b13 expression
US11690921B2 (en) 2018-05-18 2023-07-04 Sangamo Therapeutics, Inc. Delivery of target specific nucleases
AU2019282824C1 (en) 2018-06-08 2026-04-23 Intellia Therapeutics, Inc. Modified guide RNAS for gene editing
CA3103528A1 (en) 2018-06-19 2019-12-26 The Board Of Regents Of The University Of Texas System Lipid nanoparticle compositions for delivery of mrna and long nucleic acids

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