CA3116555A1 - Programmable dna base editing by nme2cas9-deaminase fusion proteins - Google Patents

Programmable dna base editing by nme2cas9-deaminase fusion proteins Download PDF

Info

Publication number
CA3116555A1
CA3116555A1 CA3116555A CA3116555A CA3116555A1 CA 3116555 A1 CA3116555 A1 CA 3116555A1 CA 3116555 A CA3116555 A CA 3116555A CA 3116555 A CA3116555 A CA 3116555A CA 3116555 A1 CA3116555 A1 CA 3116555A1
Authority
CA
Canada
Prior art keywords
nme2cas9
protein
editing
cas9
virus
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CA3116555A
Other languages
English (en)
French (fr)
Inventor
Erik J. Sontheimer
Xin Gao
Aamir MIR
Alireza EDRAKI
Scot A. Wolfe
Pengpeng LIU
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Massachusetts Amherst
Original Assignee
University of Massachusetts Amherst
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of Massachusetts Amherst filed Critical University of Massachusetts Amherst
Publication of CA3116555A1 publication Critical patent/CA3116555A1/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • C12N15/625—DNA sequences coding for fusion proteins containing a sequence coding for a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90—Stable introduction of foreign DNA into chromosome
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
    • C12Y305/04—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in cyclic amidines (3.5.4)
    • C12Y305/04004—Adenosine deaminase (3.5.4.4)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
    • C12Y305/04—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in cyclic amidines (3.5.4)
    • C12Y305/04005—Cytidine deaminase (3.5.4.5)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14142—Use of virus, viral particle or viral elements as a vector virus or viral particle as vehicle, e.g. encapsulating small organic molecule
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14171—Demonstrated in vivo effect
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/80—Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Virology (AREA)
  • Mycology (AREA)
  • Cell Biology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
CA3116555A 2018-10-15 2019-10-15 Programmable dna base editing by nme2cas9-deaminase fusion proteins Pending CA3116555A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862745666P 2018-10-15 2018-10-15
US62/745,666 2018-10-15
PCT/US2019/056341 WO2020081568A1 (en) 2018-10-15 2019-10-15 Programmable dna base editing by nme2cas9-deaminase fusion proteins

Publications (1)

Publication Number Publication Date
CA3116555A1 true CA3116555A1 (en) 2020-04-23

Family

ID=68621349

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3116555A Pending CA3116555A1 (en) 2018-10-15 2019-10-15 Programmable dna base editing by nme2cas9-deaminase fusion proteins

Country Status (16)

Country Link
US (1) US12577546B2 (https=)
EP (1) EP3867367A1 (https=)
JP (2) JP7588856B2 (https=)
KR (1) KR20210077732A (https=)
CN (1) CN113166743B (https=)
BR (1) BR112021007123A2 (https=)
CA (1) CA3116555A1 (https=)
CO (1) CO2021006336A2 (https=)
EA (1) EA202191033A1 (https=)
IL (2) IL282267B2 (https=)
MX (1) MX2021004301A (https=)
MY (1) MY209774A (https=)
PH (1) PH12021550854A1 (https=)
SG (1) SG11202103722TA (https=)
WO (1) WO2020081568A1 (https=)
ZA (1) ZA202103277B (https=)

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9340799B2 (en) 2013-09-06 2016-05-17 President And Fellows Of Harvard College MRNA-sensing switchable gRNAs
WO2019023680A1 (en) 2017-07-28 2019-01-31 President And Fellows Of Harvard College METHODS AND COMPOSITIONS FOR EVOLUTION OF BASIC EDITORS USING PHAGE-ASSISTED CONTINUOUS EVOLUTION (PACE)
WO2019118949A1 (en) 2017-12-15 2019-06-20 The Broad Institute, Inc. Systems and methods for predicting repair outcomes in genetic engineering
EP3797160A1 (en) 2018-05-23 2021-03-31 The Broad Institute Inc. Base editors and uses thereof
US12522807B2 (en) 2018-07-09 2026-01-13 The Broad Institute, Inc. RNA programmable epigenetic RNA modifiers and uses thereof
WO2020092453A1 (en) 2018-10-29 2020-05-07 The Broad Institute, Inc. Nucleobase editors comprising geocas9 and uses thereof
US12351837B2 (en) 2019-01-23 2025-07-08 The Broad Institute, Inc. Supernegatively charged proteins and uses thereof
JP7657726B2 (ja) 2019-03-19 2025-04-07 ザ ブロード インスティテュート，インコーポレーテッド 編集ヌクレオチド配列を編集するための方法および組成物
US12473543B2 (en) 2019-04-17 2025-11-18 The Broad Institute, Inc. Adenine base editors with reduced off-target effects
US12435330B2 (en) 2019-10-10 2025-10-07 The Broad Institute, Inc. Methods and compositions for prime editing RNA
DE112021002672T5 (de) 2020-05-08 2023-04-13 President And Fellows Of Harvard College Vefahren und zusammensetzungen zum gleichzeitigen editieren beider stränge einer doppelsträngigen nukleotid-zielsequenz
GB202010348D0 (en) 2020-07-06 2020-08-19 Univ Wageningen Base editing tools
CA3204997A1 (en) 2020-12-11 2022-06-16 Intellia Therapeutics, Inc. Compositions and methods for reducing mhc class ii in a cell
CR20230305A (es) 2020-12-11 2023-11-10 Intellia Therapeutics Inc Polinucleótidos, composiciones y métodos para la edición del genoma que implican desaminación
AU2021409732A1 (en) 2020-12-23 2023-07-20 Intellia Therapeutics, Inc. Compositions and methods for reducing hla-a in a cell
TW202242101A (zh) 2020-12-23 2022-11-01 美商英特利亞醫療公司 用於細胞中基因修飾ciita之組合物及方法
EP4426821A1 (en) * 2021-11-02 2024-09-11 University of Massachusetts Nme2cas9 inlaid domain fusion proteins
EP4426822A2 (en) 2021-11-03 2024-09-11 Intellia Therapeutics, Inc. Polynucleotides, compositions, and methods for genome editing
AU2023248451A1 (en) * 2022-04-04 2024-10-17 President And Fellows Of Harvard College Cas9 variants having non-canonical pam specificities and uses thereof
WO2023227669A2 (en) * 2022-05-26 2023-11-30 UCB Biopharma SRL Novel nucleic acid-editing proteins
EP4540389A2 (en) 2022-06-16 2025-04-23 Intellia Therapeutics, Inc. Compositions and methods for reducing mhc class i in a cell
CN119384498A (zh) 2022-06-16 2025-01-28 因特利亚治疗公司 用于对细胞进行遗传修饰的方法和组合物
EP4540388A2 (en) 2022-06-16 2025-04-23 Intellia Therapeutics, Inc. Compositions and methods for genomic editing
CN115206456B (zh) * 2022-07-13 2023-04-25 黑龙江大学 基于属性编辑流的分子生成方法
CN115851775B (zh) * 2022-10-18 2023-08-04 哈尔滨工业大学 一种Cas9蛋白抑制剂及其应用
CN115716880A (zh) * 2022-12-07 2023-02-28 云舟生物科技(广州)股份有限公司 一种核定位荧光蛋白及其应用
WO2024138189A2 (en) 2022-12-22 2024-06-27 Intellia Therapeutics, Inc. Methods for analyzing nucleic acid cargos of lipid nucleic acid assemblies
WO2024186890A1 (en) 2023-03-06 2024-09-12 Intellia Therapeutics, Inc. Compositions and methods for hepatitis b virus (hbv) genome editing
US20240417707A1 (en) * 2023-05-11 2024-12-19 University Of Massachusetts Compositions and methods for improved genome editing with nme2cas9 and nme2-smucas9 variants
AU2024324870A1 (en) 2023-08-14 2026-02-12 Intellia Therapeutics, Inc. Compositions and methods for genetically modifying transforming growth factor beta receptor type 2 (tgfβr2)
TW202521564A (zh) 2023-08-14 2025-06-01 美商英特利亞醫療公司 用於基於細胞之療法的ｃｄ７０ ｃａｒ－ｔ組合物及方法
TW202515994A (zh) 2023-08-14 2025-04-16 美商英特利亞醫療公司 用於對ｃｄ７０進行基因修飾之組合物及方法
WO2025137301A1 (en) 2023-12-20 2025-06-26 Intellia Therapeutics, Inc. Methods for rapid engineering of cells
WO2025255308A1 (en) 2024-06-07 2025-12-11 Intellia Therapeutics, Inc. Cd8 co-receptor chimeric polypeptides in tcr cell therapy
WO2026014914A1 (ko) * 2024-07-10 2026-01-15 서울대학교산학협력단 Adar 효소 또는 이의 변이체를 이용한 단일 염기 교정기

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL154598B (nl) 1970-11-10 1977-09-15 Organon Nv Werkwijze voor het aantonen en bepalen van laagmoleculire verbindingen en van eiwitten die deze verbindingen specifiek kunnen binden, alsmede testverpakking.
US3817837A (en) 1971-05-14 1974-06-18 Syva Corp Enzyme amplification assay
US3939350A (en) 1974-04-29 1976-02-17 Board Of Trustees Of The Leland Stanford Junior University Fluorescent immunoassay employing total reflection for activation
US3996345A (en) 1974-08-12 1976-12-07 Syva Company Fluorescence quenching with immunological pairs in immunoassays
US4275149A (en) 1978-11-24 1981-06-23 Syva Company Macromolecular environment control in specific receptor assays
US4277437A (en) 1978-04-05 1981-07-07 Syva Company Kit for carrying out chemically induced fluorescence immunoassay
US4366241A (en) 1980-08-07 1982-12-28 Syva Company Concentrating zone method in heterogeneous immunoassays
MX374090B (es) * 2013-03-14 2025-03-05 Caribou Biosciences Inc Composiciones y métodos de ácidos nucleicos dirigidos al ácido nucleico.
US20150165054A1 (en) 2013-12-12 2015-06-18 President And Fellows Of Harvard College Methods for correcting caspase-9 point mutations
JP7109784B2 (ja) * 2015-10-23 2022-08-01 プレジデント アンド フェローズ オブ ハーバード カレッジ 遺伝子編集のための進化したＣａｓ９蛋白質
KR102547316B1 (ko) 2016-08-03 2023-06-23 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 아데노신 핵염기 편집제 및 그의 용도
WO2018152197A1 (en) * 2017-02-15 2018-08-23 Massachusetts Institute Of Technology Dna writers, molecular recorders and uses thereof
KR102772726B1 (ko) 2017-02-15 2025-02-25 키진 엔.브이. 식물 세포에서 표적 유전적 변형 방법
CA3057192A1 (en) 2017-03-23 2018-09-27 President And Fellows Of Harvard College Nucleobase editors comprising nucleic acid programmable dna binding proteins

Also Published As

Publication number Publication date
AU2019362874A1 (en) 2021-05-27
US12577546B2 (en) 2026-03-17
JP7588856B2 (ja) 2024-11-25
IL282267B1 (en) 2025-11-01
EA202191033A1 (ru) 2021-12-21
CN113166743A (zh) 2021-07-23
WO2020081568A1 (en) 2020-04-23
MY209774A (en) 2025-08-03
JP2024121000A (ja) 2024-09-05
ZA202103277B (en) 2025-09-25
EP3867367A1 (en) 2021-08-25
CO2021006336A2 (es) 2021-10-29
IL323589A (en) 2025-11-01
SG11202103722TA (en) 2021-05-28
BR112021007123A2 (pt) 2021-08-10
KR20210077732A (ko) 2021-06-25
US20220290113A1 (en) 2022-09-15
IL282267B2 (en) 2026-03-01
MX2021004301A (es) 2021-08-05
JP2022508716A (ja) 2022-01-19
IL282267A (en) 2021-05-31
PH12021550854A1 (en) 2022-07-25
CN113166743B (zh) 2026-04-07

Similar Documents

Publication Publication Date Title
US12577546B2 (en) Programmable DNA base editing by Nme2Cas9-deaminase fusion proteins
US12435320B2 (en) CRISPR having or associated with destabilization domains
Edraki et al. A compact, high-accuracy Cas9 with a dinucleotide PAM for in vivo genome editing
US11624078B2 (en) Protected guide RNAS (pgRNAS)
US20250197889A1 (en) Targeted CRISPR Delivery Platforms
JP2017527256A (ja) ＨＢＶ及びウイルス性疾患及び障害のためのＣＲＩＳＰＲ−Ｃａｓ系及び組成物の送達、使用及び治療適用
CN120344660A (zh) 基因编辑组分、系统和使用方法
TW202112229A (zh) 包含人化白蛋白基因座之非人的動物
US20240408238A1 (en) Nme2cas9 inlaid domain fusion proteins
AU2019362874B2 (en) Programmable DNA base editing by Nme2Cas9-deaminase fusion proteins
US20250332287A1 (en) Identification of tissue-specific extragenic safe harbors for gene therapy approaches
US20240417707A1 (en) Compositions and methods for improved genome editing with nme2cas9 and nme2-smucas9 variants
HK40051421A (en) Programmable dna base editing by nme2cas9-deaminase fusion proteins
HK40036538A (en) Targeted crispr delivery platforms

Legal Events

Date Code Title Description
MFA Maintenance fee for application paid

Free format text: FEE DESCRIPTION TEXT: MF (APPLICATION, 5TH ANNIV.) - STANDARD

Year of fee payment: 5

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-1-1-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20241011

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-1-1-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT DETERMINED COMPLIANT

Effective date: 20241011

Free format text: ST27 STATUS EVENT CODE: A-1-1-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT PAID IN FULL

Effective date: 20241011

D11 Substantive examination requested

Free format text: ST27 STATUS EVENT CODE: A-1-1-D10-D11-D117 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: REQUEST FOR EXAMINATION RECEIVED

Effective date: 20241015

P11 Amendment of application requested

Free format text: ST27 STATUS EVENT CODE: A-1-1-P10-P11-P101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: AMENDMENT RECEIVED - VOLUNTARY AMENDMENT

Effective date: 20241015

W00 Other event occurred

Free format text: ST27 STATUS EVENT CODE: A-1-1-W10-W00-W111 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: CORRESPONDENT DETERMINED COMPLIANT

Effective date: 20250203

D00 Search and/or examination requested or commenced

Free format text: ST27 STATUS EVENT CODE: A-1-1-D10-D00-D118 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: REQUEST FOR EXAMINATION REQUIREMENTS DETERMINED COMPLIANT

Effective date: 20250210

P11 Amendment of application requested

Free format text: ST27 STATUS EVENT CODE: A-1-1-P10-P11-P102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: AMENDMENT DETERMINED COMPLIANT

Effective date: 20250210

P13 Application amended

Free format text: ST27 STATUS EVENT CODE: A-1-1-P10-P13-X000 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: APPLICATION AMENDED

Effective date: 20250210

W00 Other event occurred

Free format text: ST27 STATUS EVENT CODE: A-1-1-W10-W00-W111 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: CORRESPONDENT DETERMINED COMPLIANT

Effective date: 20250210

W00 Other event occurred

Free format text: ST27 STATUS EVENT CODE: A-1-1-W10-W00-W100 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: LETTER SENT

Effective date: 20250506

D11 Substantive examination requested

Free format text: ST27 STATUS EVENT CODE: A-1-2-D10-D11-D155 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: ALL REQUIREMENTS FOR EXAMINATION DETERMINED COMPLIANT

Effective date: 20250507

MFA Maintenance fee for application paid

Free format text: FEE DESCRIPTION TEXT: MF (APPLICATION, 6TH ANNIV.) - STANDARD

Year of fee payment: 6

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-2-2-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20251010

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-2-2-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT PAID IN FULL

Effective date: 20251010