PL2578685T3 - Rna zawierający zmodyfikowane nukleozydy i sposoby jego zastosowania - Google Patents

Rna zawierający zmodyfikowane nukleozydy i sposoby jego zastosowania

Info

Publication number
PL2578685T3
PL2578685T3 PL12008048T PL12008048T PL2578685T3 PL 2578685 T3 PL2578685 T3 PL 2578685T3 PL 12008048 T PL12008048 T PL 12008048T PL 12008048 T PL12008048 T PL 12008048T PL 2578685 T3 PL2578685 T3 PL 2578685T3
Authority
PL
Poland
Prior art keywords
methods
modified nucleosides
containing modified
rna containing
rna
Prior art date
Application number
PL12008048T
Other languages
English (en)
Inventor
Katalin Kariko
Drew Weissman
Original Assignee
The Trustees Of The University Of Pennsylvania
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 The Trustees Of The University Of Pennsylvania filed Critical The Trustees Of The University Of Pennsylvania
Publication of PL2578685T3 publication Critical patent/PL2578685T3/pl

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A61K48/0066—Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1816—Erythropoietin [EPO]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/50—Hydrolases (3) acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
    • A61K48/0025—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid
    • A61K48/0041—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid the non-active part being polymeric
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4712—Cystic fibrosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/505—Erythropoietin [EPO]
    • 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
    • C12N15/117—Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
    • 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
    • C12N15/67—General methods for enhancing the expression
    • 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
    • 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
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • 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
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0696—Artificially induced pluripotent stem cells, e.g. iPS
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • 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)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • 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
    • C12N2310/17—Immunomodulatory nucleic acids
    • 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
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • 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
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
    • 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
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/335—Modified T or U
    • 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
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/40—Regulators of development
    • 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
    • C12N2800/95—Protection of vectors from inactivation by agents such as antibodies or enzymes, e.g. using polymers

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Microbiology (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • Toxicology (AREA)
  • Plant Pathology (AREA)
  • Cell Biology (AREA)
  • Pulmonology (AREA)
  • Transplantation (AREA)
  • Developmental Biology & Embryology (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PL12008048T 2005-08-23 2006-08-21 Rna zawierający zmodyfikowane nukleozydy i sposoby jego zastosowania PL2578685T3 (pl)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US71016405P 2005-08-23 2005-08-23
EP12008048.6A EP2578685B1 (en) 2005-08-23 2006-08-21 Rna containing modified nucleosides and methods of use thereof
EP06813536A EP1979364A4 (en) 2005-08-23 2006-08-21 RNA-containing Modified Nucleosides and Method Therefor
PCT/US2006/032372 WO2007024708A2 (en) 2005-08-23 2006-08-21 Rna containing modified nucleosides and methods of use thereof

Publications (1)

Publication Number Publication Date
PL2578685T3 true PL2578685T3 (pl) 2020-01-31

Family

ID=37772217

Family Applications (1)

Application Number Title Priority Date Filing Date
PL12008048T PL2578685T3 (pl) 2005-08-23 2006-08-21 Rna zawierający zmodyfikowane nukleozydy i sposoby jego zastosowania

Country Status (13)

Country Link
US (10) US8278036B2 (pl)
EP (6) EP2578685B1 (pl)
DK (1) DK2578685T3 (pl)
ES (2) ES2735531T3 (pl)
HR (1) HRP20230113T3 (pl)
HU (1) HUE043492T2 (pl)
LT (1) LT2578685T (pl)
PL (1) PL2578685T3 (pl)
PT (1) PT2578685T (pl)
RS (1) RS63964B1 (pl)
SI (1) SI3611266T1 (pl)
TR (1) TR201909609T4 (pl)
WO (1) WO2007024708A2 (pl)

Families Citing this family (573)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1903054A3 (de) 2001-06-05 2008-07-23 CureVac GmbH Stabilisierte mRNA mit erhöhtem G/C-Gehalt und optimierter Codon Usage für die Gentherapie
DE10162480A1 (de) 2001-12-19 2003-08-07 Ingmar Hoerr Die Applikation von mRNA für den Einsatz als Therapeutikum gegen Tumorerkrankungen
DE10347710B4 (de) 2003-10-14 2006-03-30 Johannes-Gutenberg-Universität Mainz Rekombinante Impfstoffe und deren Verwendung
US9012219B2 (en) * 2005-08-23 2015-04-21 The Trustees Of The University Of Pennsylvania RNA preparations comprising purified modified RNA for reprogramming cells
HUE043492T2 (hu) 2005-08-23 2019-08-28 Univ Pennsylvania Módosított nukleozidokat tartalmazó RNS és eljárások az alkalmazására
US20070054873A1 (en) * 2005-08-26 2007-03-08 Protiva Biotherapeutics, Inc. Glucocorticoid modulation of nucleic acid-mediated immune stimulation
DE102005046490A1 (de) 2005-09-28 2007-03-29 Johannes-Gutenberg-Universität Mainz Modifikationen von RNA, die zu einer erhöhten Transkriptstabilität und Translationseffizienz führen
WO2007051303A1 (en) 2005-11-02 2007-05-10 Protiva Biotherapeutics, Inc. MODIFIED siRNA MOLECULES AND USES THEREOF
US7915399B2 (en) * 2006-06-09 2011-03-29 Protiva Biotherapeutics, Inc. Modified siRNA molecules and uses thereof
AU2007310982A1 (en) * 2006-10-18 2008-04-24 Marina Biotech, Inc. Nicked or gapped nucleic acid molecules and uses thereof
DE102006051516A1 (de) * 2006-10-31 2008-05-08 Curevac Gmbh (Basen-)modifizierte RNA zur Expressionssteigerung eines Proteins
DE102007001370A1 (de) * 2007-01-09 2008-07-10 Curevac Gmbh RNA-kodierte Antikörper
JP2010519912A (ja) * 2007-03-02 2010-06-10 エムディーアールエヌエー，インコーポレイテッド Ｒａｓ遺伝子の発現を抑制するための核酸化合物およびその使用
WO2008109377A1 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting vegf family gene expression and uses thereof
US20100112687A1 (en) * 2007-03-02 2010-05-06 Mdrna, Inc. Nucleic acid compounds for inhibiting erbb family gene expression and uses thereof
WO2009046739A1 (en) * 2007-10-09 2009-04-16 Curevac Gmbh Composition for treating prostate cancer (pca)
WO2009127230A1 (en) * 2008-04-16 2009-10-22 Curevac Gmbh MODIFIED (m)RNA FOR SUPPRESSING OR AVOIDING AN IMMUNOSTIMULATORY RESPONSE AND IMMUNOSUPPRESSIVE COMPOSITION
WO2010088927A1 (en) * 2009-02-09 2010-08-12 Curevac Gmbh Use of pei for the improvement of endosomal release and expression of transfected nucleic acids, complexed with cationic or polycationic compounds
WO2010123501A1 (en) * 2009-04-22 2010-10-28 Massachusetts Institute Of Technology Innate immune suppression enables repeated delivery of long rna molecules
US10837020B2 (en) 2009-04-22 2020-11-17 Massachusetts Institute Of Technology Innate immune suppression enables repeated delivery of long RNA molecules
EP2451475A2 (en) 2009-07-06 2012-05-16 Novartis AG Self replicating rna molecules and uses thereof
DE102009050308A1 (de) 2009-10-22 2011-05-05 Ludwig-Maximilians-Universität München RNA mit einer Kombination aus unmodifizierten und modifizierten Nucleotiden zur Proteinexpression
EP3165234B1 (de) * 2009-07-31 2019-04-03 ethris GmbH Rna mit einer kombination aus unmodifizierten und modifizierten nucleotiden zur proteinexpression
WO2011026185A1 (en) * 2009-09-04 2011-03-10 Murdoch Childrens Research Institute An assay for monitoring a neurological condition
PL3338765T3 (pl) 2009-12-01 2019-06-28 Translate Bio, Inc. Pochodna steroidowa dla dostarczania mrna w ludzkich chorobach genetycznych
KR101878502B1 (ko) 2009-12-07 2018-07-13 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 세포 리프로그래밍을 위한 정제된 변형 ｒｎａ를 포함하는 ｒｎａ 제제
AU2015215938B2 (en) * 2009-12-07 2018-01-18 The Trustees Of The University Of Pennsylvania RNA preparations comprising purified modified RNA for reprogramming cells
EP2338520A1 (de) 2009-12-21 2011-06-29 Ludwig Maximilians Universität Konjugat mit Zielfindungsligand und dessen Verwendung
EP3072961A1 (en) * 2010-04-16 2016-09-28 Children's Medical Center Corporation Sustained polypeptide expression from synthetic, modified rnas and uses thereof
AU2011276234B2 (en) 2010-07-06 2016-02-25 Glaxosmithkline Biologicals S.A. Liposomes with lipids having an advantageous pKa- value for RNA delivery
ES2646669T3 (es) 2010-07-06 2017-12-14 Glaxosmithkline Biologicals Sa Procedimientos de aumento de una respuesta inmunitaria mediante el suministro de ARN
US11291635B2 (en) 2010-07-06 2022-04-05 Glaxosmithkline Biological Sa Virion-like delivery particles for self-replicating RNA molecules
SI2591114T1 (sl) 2010-07-06 2016-10-28 Glaxosmithkline Biologicals S.A. Imunizacija velikih sesalcev z majhnimi odmerki RNA
CA2807552A1 (en) 2010-08-06 2012-02-09 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
WO2012019630A1 (en) 2010-08-13 2012-02-16 Curevac Gmbh Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded protein
WO2012031043A1 (en) 2010-08-31 2012-03-08 Novartis Ag Pegylated liposomes for delivery of immunogen-encoding rna
ES3005233T3 (en) 2010-10-01 2025-03-14 Modernatx Inc Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
EP3520813B1 (en) 2010-10-11 2023-04-19 GlaxoSmithKline Biologicals S.A. Antigen delivery platforms
US8853377B2 (en) 2010-11-30 2014-10-07 Shire Human Genetic Therapies, Inc. mRNA for use in treatment of human genetic diseases
JP2014511687A (ja) 2011-03-31 2014-05-19 モデルナ セラピューティクス インコーポレイテッド 工学操作された核酸の送達および製剤
JP2014511694A (ja) 2011-04-03 2014-05-19 ザ ジェネラル ホスピタル コーポレーション ドゥーイング ビジネス アズ マサチューセッツ ジェネラル ホスピタル 修飾型ｒｎａ（ｍｏｄ−ｒｎａ）を使用する効率的なインビボタンパク質発現
CN103687957A (zh) * 2011-05-17 2014-03-26 现代治疗公司 工程化核酸及其用于非人类脊椎动物的方法
PL3892295T3 (pl) 2011-05-24 2023-07-24 BioNTech SE Zindywidualizowane szczepionki przeciwnowotworowe
PT2717893T (pt) * 2011-06-08 2019-08-20 Translate Bio Inc Composições de nanopartículas lipídicas e métodos para transferência de arnm
EP3854413A1 (en) 2011-07-06 2021-07-28 GlaxoSmithKline Biologicals SA Immunogenic combination compositions and uses thereof
US9464124B2 (en) 2011-09-12 2016-10-11 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
EP2763701B1 (en) 2011-10-03 2018-12-19 Moderna Therapeutics, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
WO2013078199A2 (en) * 2011-11-23 2013-05-30 Children's Medical Center Corporation Methods for enhanced in vivo delivery of synthetic, modified rnas
RU2691027C2 (ru) 2011-12-05 2019-06-07 Фэктор Байосайенс Инк. Способы и препараты для трансфекции клеток
US8497124B2 (en) 2011-12-05 2013-07-30 Factor Bioscience Inc. Methods and products for reprogramming cells to a less differentiated state
ES3065854T3 (en) 2011-12-07 2026-05-08 Alnylam Pharmaceuticals Inc Biodegradable lipids for the delivery of active agents
JP2015501844A (ja) * 2011-12-16 2015-01-19 モデルナ セラピューティクス インコーポレイテッドＭｏｄｅｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． 修飾ヌクレオシド、ヌクレオチドおよび核酸組成物
CN104968354A (zh) * 2011-12-21 2015-10-07 现代治疗公司 增加器官或器官外植体的活力或寿命的方法
EP4721752A2 (en) 2011-12-30 2026-04-08 Cellscript, Llc Herstellung und verwendung von in vitro-synthetisierter ssrna zur einführung in säugetierzellen zur induktion einer biologischen oder biochemischen wirkung
WO2013120499A1 (en) 2012-02-15 2013-08-22 Curevac Gmbh Nucleic acid comprising or coding for a histone stem-loop and a poly (a) sequence or a polyadenylation signal for increasing the expression of an encoded pathogenic antigen
WO2013120500A1 (en) 2012-02-15 2013-08-22 Curevac Gmbh Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded tumour antigen
WO2013120497A1 (en) 2012-02-15 2013-08-22 Curevac Gmbh Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded therapeutic protein
WO2013120498A1 (en) 2012-02-15 2013-08-22 Curevac Gmbh Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded allergenic antigen or an autoimmune self-antigen
WO2013143555A1 (en) 2012-03-26 2013-10-03 Biontech Ag Rna formulation for immunotherapy
SG11201405545XA (en) * 2012-03-27 2014-11-27 Curevac Gmbh Artificial nucleic acid molecules comprising a 5'top utr
CA2859452C (en) 2012-03-27 2021-12-21 Curevac Gmbh Artificial nucleic acid molecules for improved protein or peptide expression
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
CN108949772A (zh) * 2012-04-02 2018-12-07 现代泰克斯公司 用于产生与人类疾病相关的生物制剂和蛋白质的修饰多核苷酸
WO2013151663A1 (en) 2012-04-02 2013-10-10 modeRNA Therapeutics Modified polynucleotides for the production of membrane proteins
US10501513B2 (en) 2012-04-02 2019-12-10 Modernatx, Inc. Modified polynucleotides for the production of oncology-related proteins and peptides
US9254311B2 (en) 2012-04-02 2016-02-09 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins
US9572897B2 (en) 2012-04-02 2017-02-21 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
WO2013163628A2 (en) 2012-04-27 2013-10-31 Duke University Genetic correction of mutated genes
AU2013267161A1 (en) 2012-05-31 2014-11-20 Sorrento Therapeutics, Inc. Antigen binding proteins that bind PD-L1
WO2013185069A1 (en) * 2012-06-08 2013-12-12 Shire Human Genetic Therapies, Inc. Pulmonary delivery of mrna to non-lung target cells
US20150126589A1 (en) * 2012-06-08 2015-05-07 Ethris Gmbh Pulmonary Delivery of Messenger RNA
WO2013185067A1 (en) 2012-06-08 2013-12-12 Shire Human Genetic Therapies, Inc. Nuclease resistant polynucleotides and uses thereof
WO2014028429A2 (en) 2012-08-14 2014-02-20 Moderna Therapeutics, Inc. Enzymes and polymerases for the synthesis of rna
HK1212384A1 (en) 2012-09-07 2016-06-10 F. Hoffmann-La Roche Ag Methods and compositions for producing induced hepatocytes
US9376489B2 (en) 2012-09-07 2016-06-28 Novartis Ag IL-18 binding molecules
EP2914728B1 (en) 2012-11-01 2020-07-08 Factor Bioscience Inc. Methods and products for expressing proteins in cells
ES2921623T3 (es) * 2012-11-26 2022-08-30 Modernatx Inc ARN modificado terminalmente
EP2925348B1 (en) 2012-11-28 2019-03-06 BioNTech RNA Pharmaceuticals GmbH Individualized vaccines for cancer
EP2929035A1 (en) * 2012-12-07 2015-10-14 Shire Human Genetic Therapies, Inc. Lipidic nanoparticles for mrna delivering
US20150315541A1 (en) * 2012-12-13 2015-11-05 Moderna Therapeutics, Inc. Modified polynucleotides for altering cell phenotype
JP2016504050A (ja) 2013-01-17 2016-02-12 モデルナ セラピューティクス インコーポレイテッドＭｏｄｅｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． 細胞表現型の改変のためのシグナルセンサーポリヌクレオチド
MX371052B (es) 2013-02-08 2020-01-14 Novartis Ag Anticuerpos anti-il-17a y su uso en el tratamiento de trastornos autoinmunes e inflamatorios.
PT2959005T (pt) 2013-02-22 2021-12-30 Univ Leland Stanford Junior Utilização médica relacionada com extensão de telómero
US20160024181A1 (en) * 2013-03-13 2016-01-28 Moderna Therapeutics, Inc. Long-lived polynucleotide molecules
US20160032316A1 (en) 2013-03-14 2016-02-04 The Trustees Of The University Of Pennsylvania Purification and Purity Assessment of RNA Molecules Synthesized with Modified Nucleosides
EP2968586B1 (en) 2013-03-14 2018-07-25 Translate Bio, Inc. Cftr mrna compositions and related methods and uses
US10258698B2 (en) 2013-03-14 2019-04-16 Modernatx, Inc. Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions
ES2981185T3 (es) 2013-03-14 2024-10-07 Translate Bio Inc Métodos para la purificación de ARN mensajero
WO2014160284A1 (en) * 2013-03-14 2014-10-02 The Trustees Of The University Of Pennsylvania Compositions and methods for treatment of stroke
EP2971033B8 (en) 2013-03-15 2019-07-10 ModernaTX, Inc. Manufacturing methods for production of rna transcripts
EP2971161B1 (en) 2013-03-15 2018-12-26 ModernaTX, Inc. Ribonucleic acid purification
US9957515B2 (en) 2013-03-15 2018-05-01 Cibus Us Llc Methods and compositions for targeted gene modification
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
EP2983804A4 (en) 2013-03-15 2017-03-01 Moderna Therapeutics, Inc. Ion exchange purification of mrna
US10077439B2 (en) 2013-03-15 2018-09-18 Modernatx, Inc. Removal of DNA fragments in mRNA production process
US9828582B2 (en) 2013-03-19 2017-11-28 Duke University Compositions and methods for the induction and tuning of gene expression
DE102013005361A1 (de) * 2013-03-28 2014-10-02 Eberhard Karls Universität Tübingen Medizinische Fakultät Polyribonucleotid
JP2016522679A (ja) 2013-04-04 2016-08-04 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 ＣＲＩＳＰＲ／Ｃａｓ系を用いたゲノム編集の治療的使用
WO2014180490A1 (en) 2013-05-10 2014-11-13 Biontech Ag Predicting immunogenicity of t cell epitopes
EP2996697B1 (en) 2013-05-15 2019-06-26 Robert Kruse Intracellular translation of circular rna
US12064484B2 (en) 2013-06-28 2024-08-20 Ethris Gmbh Compositions for introducing RNA into cells
HUE056760T2 (hu) 2013-07-11 2022-03-28 Modernatx Inc A CRISPR-hez kapcsolódó fehérjéket és a szintetikus SGRNS-ket kódoló szintetikus polinukleotidokat tartalmazó készítmények és felhasználási módjaik
ES2929549T3 (es) 2013-07-26 2022-11-30 Kyoto Prefectural Public Univ Corp Osteoblasto y método de preparación del mismo
US20160194625A1 (en) 2013-09-03 2016-07-07 Moderna Therapeutics, Inc. Chimeric polynucleotides
WO2015048744A2 (en) 2013-09-30 2015-04-02 Moderna Therapeutics, Inc. Polynucleotides encoding immune modulating polypeptides
WO2015051169A2 (en) 2013-10-02 2015-04-09 Moderna Therapeutics, Inc. Polynucleotide molecules and uses thereof
KR20160067219A (ko) 2013-10-03 2016-06-13 모더나 세라퓨틱스, 인코포레이티드 저밀도 지단백질 수용체를 암호화하는 폴리뉴클레오타이드
DE102013111099B4 (de) 2013-10-08 2023-11-30 Eberhard Karls Universität Tübingen Medizinische Fakultät Permanente Genkorrektur mittels nukleotidmodifizierter messenger RNA
MX2016005239A (es) 2013-10-22 2016-08-12 Shire Human Genetic Therapies Tratamiento con acido ribonucleico mensajero para la fenilcetonuria.
US11224642B2 (en) 2013-10-22 2022-01-18 Translate Bio, Inc. MRNA therapy for argininosuccinate synthetase deficiency
WO2015061467A1 (en) 2013-10-22 2015-04-30 Shire Human Genetic Therapies, Inc. Lipid formulations for delivery of messenger rna
WO2015065505A1 (en) * 2013-10-29 2015-05-07 Duke University Use of cyp27a1 inhibitors, statin, or lxr antagonists alone or in combination with conventional therapy for the treatment of breast cancer
EP3542802A1 (en) 2013-11-01 2019-09-25 CureVac AG Modified rna with decreased immunostimulatory properties
ES2806575T3 (es) 2013-11-01 2021-02-18 Curevac Ag ARN modificado con propiedades inmunoestimuladoras disminuidas
US10801070B2 (en) 2013-11-25 2020-10-13 The Broad Institute, Inc. Compositions and methods for diagnosing, evaluating and treating cancer
US11725237B2 (en) 2013-12-05 2023-08-15 The Broad Institute Inc. Polymorphic gene typing and somatic change detection using sequencing data
EP3082760A1 (en) 2013-12-19 2016-10-26 Novartis AG LEPTIN mRNA COMPOSITIONS AND FORMULATIONS
NZ721908A (en) 2013-12-20 2022-12-23 Massachusetts Gen Hospital Combination therapy with neoantigen vaccine
WO2015101415A1 (en) 2013-12-30 2015-07-09 Curevac Gmbh Artificial nucleic acid molecules
US11254951B2 (en) 2014-12-30 2022-02-22 Curevac Ag Artificial nucleic acid molecules
CN111304231A (zh) 2013-12-30 2020-06-19 库瑞瓦格股份公司 人工核酸分子
CN105940110A (zh) 2014-01-31 2016-09-14 菲克特生物科学股份有限公司 用于核酸产生和递送的方法和产品
AU2015218576B2 (en) 2014-02-24 2020-02-27 Sangamo Therapeutics, Inc. Methods and compositions for nuclease-mediated targeted integration
EP3110954A1 (en) 2014-02-26 2017-01-04 Ethris GmbH Compositions for gastrointestinal administration of rna
ES2974625T3 (es) 2014-03-14 2024-06-28 Cibus Us Llc Procedimientos y composiciones para aumentar la eficacia de la modificación génica dirigida mediante reparación génica mediada por oligonucleótidos
EP3125945B1 (en) * 2014-04-01 2019-09-11 Institut National de la Sante et de la Recherche Medicale (INSERM) Capped and uncapped rna molecules and block copolymers for intracellular delivery of rna
DK3134131T3 (en) 2014-04-23 2022-02-07 Modernatx Inc Nucleic acid vaccines
JP6571679B2 (ja) 2014-04-25 2019-09-04 トランスレイト バイオ， インコーポレイテッド メッセンジャーｒｎａの精製方法
US10022455B2 (en) 2014-05-30 2018-07-17 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10837039B2 (en) 2014-06-10 2020-11-17 Curevac Real Estate Gmbh Methods and means for enhancing RNA production
GB201410693D0 (en) 2014-06-16 2014-07-30 Univ Southampton Splicing modulation
WO2015196128A2 (en) 2014-06-19 2015-12-23 Moderna Therapeutics, Inc. Alternative nucleic acid molecules and uses thereof
CA2952824C (en) 2014-06-24 2023-02-21 Shire Human Genetic Therapies, Inc. Stereochemically enriched compositions for delivery of nucleic acids
IL316479A (en) 2014-06-25 2024-12-01 Acuitas Therapeutics Inc Novel lipids and lipid nanoparticle compositions for nucleic acid delivery
US20170291939A1 (en) 2014-06-25 2017-10-12 Novartis Ag Antibodies specific for il-17a fused to hyaluronan binding peptide tags
CA2955238A1 (en) 2014-07-16 2016-01-21 Moderna Therapeutics, Inc. Circular polynucleotides
EP3169693B1 (en) 2014-07-16 2022-03-09 ModernaTX, Inc. Chimeric polynucleotides
WO2016014846A1 (en) * 2014-07-23 2016-01-28 Moderna Therapeutics, Inc. Modified polynucleotides for the production of intrabodies
KR102473092B1 (ko) 2014-09-15 2022-12-01 칠드런'즈 메디컬 센터 코포레이션 히스톤 h3-리신 트리메틸화를 제거함으로써 체세포 핵 이식(scnt) 효율을 증가시키는 방법 및 조성물
KR20170083534A (ko) 2014-09-19 2017-07-18 리제너론 파마슈티칼스 인코포레이티드 키메라 항원 수용체
WO2016045732A1 (en) 2014-09-25 2016-03-31 Biontech Rna Pharmaceuticals Gmbh Stable formulations of lipids and liposomes
EP3201339A4 (en) 2014-10-03 2018-09-19 Cold Spring Harbor Laboratory Targeted augmentation of nuclear gene output
AU2015338923B2 (en) 2014-11-02 2021-10-21 Arcturus Therapeutics, Inc. Messenger UNA molecules and uses thereof
CN107106689A (zh) 2014-11-05 2017-08-29 沃雅戈治疗公司 用于治疗帕金森病的aadc多核苷酸
EP3218508A4 (en) * 2014-11-10 2018-04-18 Modernatx, Inc. Multiparametric nucleic acid optimization
WO2016077125A1 (en) 2014-11-10 2016-05-19 Moderna Therapeutics, Inc. Alternative nucleic acid molecules containing reduced uracil content and uses thereof
ES2946969T3 (es) 2014-12-12 2023-07-28 CureVac SE Moléculas de ácido nucleico artificiales para una expresión proteica mejorada
EP3034539A1 (en) 2014-12-19 2016-06-22 Ethris GmbH Compositions for introducing nucleic acid into cells
EP4636401A2 (en) 2014-12-19 2025-10-22 The Broad Institute, Inc. Methods for profiling the t-cell-receptor repertoire
US10975442B2 (en) 2014-12-19 2021-04-13 Massachusetts Institute Of Technology Molecular biomarkers for cancer immunotherapy
JP6929791B2 (ja) 2015-02-09 2021-09-01 デューク ユニバーシティ エピゲノム編集のための組成物および方法
WO2016128060A1 (en) 2015-02-12 2016-08-18 Biontech Ag Predicting t cell epitopes useful for vaccination
WO2016131052A1 (en) 2015-02-13 2016-08-18 Factor Bioscience Inc. Nucleic acid products and methods of administration thereof
JP2018526321A (ja) * 2015-04-27 2018-09-13 ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア 適応免疫応答を誘導するためのヌクレオシド修飾ｒｎａ
CA2986235A1 (en) 2015-05-20 2016-11-24 The Broad Institute, Inc. Shared neoantigens
PL4108769T3 (pl) 2015-05-29 2024-02-05 CureVac Manufacturing GmbH Sposób wytwarzania i oczyszczania rna obejmujący co najmniej jeden etap filtracji o przepływie stycznym
TWI750122B (zh) 2015-06-09 2021-12-21 美商博德研究所有限公司 用於贅瘤疫苗之調配物及其製備方法
HUE067372T2 (hu) 2015-06-29 2024-10-28 Acuitas Therapeutics Inc Lipidek és nanoszemcsés lipid formulázások nukleinsavak beadására
CN107849574B (zh) 2015-06-30 2021-11-05 埃泽瑞斯公司 增加rna分子的翻译效率的utr
WO2017011766A1 (en) 2015-07-16 2017-01-19 Cornell University Methods of enhancing translation ability of rna molecules treatments, and kits
US11364292B2 (en) 2015-07-21 2022-06-21 Modernatx, Inc. CHIKV RNA vaccines
WO2017020026A1 (en) 2015-07-30 2017-02-02 Modernatx, Inc. Concatemeric peptide epitopes rnas
US11564893B2 (en) 2015-08-17 2023-01-31 Modernatx, Inc. Methods for preparing particles and related compositions
SI3350333T1 (sl) 2015-09-17 2022-04-29 ModernaTX,Inc. Polinukleotidi, ki zajemajo stabilizacijsko repno regijo
WO2017049286A1 (en) 2015-09-17 2017-03-23 Moderna Therapeutics, Inc. Polynucleotides containing a morpholino linker
EP3359670B2 (en) 2015-10-05 2024-02-14 ModernaTX, Inc. Methods for therapeutic administration of messenger ribonucleic acid drugs
WO2017059902A1 (en) 2015-10-07 2017-04-13 Biontech Rna Pharmaceuticals Gmbh 3' utr sequences for stabilization of rna
AU2016334804B2 (en) 2015-10-09 2022-03-31 University Of Southampton Modulation of gene expression and screening for deregulated protein expression
EP4089175A1 (en) 2015-10-13 2022-11-16 Duke University Genome engineering with type i crispr systems in eukaryotic cells
WO2017066781A1 (en) 2015-10-16 2017-04-20 Modernatx, Inc. Mrna cap analogs with modified phosphate linkage
WO2017066797A1 (en) 2015-10-16 2017-04-20 Modernatx, Inc. Trinucleotide mrna cap analogs
JP2018530587A (ja) * 2015-10-16 2018-10-18 モデルナティエックス インコーポレイテッドＭｏｄｅｒｎａＴＸ，Ｉｎｃ． ｍＲＮＡキャップ類似体およびｍＲＮＡキャッピングの方法
CN108430456B (zh) 2015-10-22 2022-01-18 摩登纳特斯有限公司 癌症疫苗
EP3364950A4 (en) 2015-10-22 2019-10-23 ModernaTX, Inc. VACCINES AGAINST TROPICAL DISEASES
WO2017070601A1 (en) 2015-10-22 2017-04-27 Modernatx, Inc. Nucleic acid vaccines for varicella zoster virus (vzv)
MD3718565T2 (ro) 2015-10-22 2022-09-30 Modernatx Inc Vaccinuri împotriva virusului respirator
EP3364981A4 (en) 2015-10-22 2019-08-07 ModernaTX, Inc. VACCINE AGAINST THE HUMAN CYTOMEGALOVIRUS
RS63986B1 (sr) 2015-10-28 2023-03-31 Acuitas Therapeutics Inc Novi lipidi i lipidne formulacije nanočestica za isporuku nukleinskih kiselina
WO2017095967A2 (en) 2015-11-30 2017-06-08 Duke University Therapeutic targets for the correction of the human dystrophin gene by gene editing and methods of use
WO2017100551A1 (en) 2015-12-09 2017-06-15 Alexion Pharmaceuticals, Inc. HETEROLOGOUS UTR SEQUENCES FOR ENHANCED mRNA EXPRESSION
WO2017100562A1 (en) * 2015-12-09 2017-06-15 Alexion Pharmaceuticals, Inc, Modified mrna encoding a uridine diphopsphate glucuronosyl transferase and uses thereof
WO2017098468A1 (en) 2015-12-09 2017-06-15 Novartis Ag Label-free analysis of rna capping efficiency using rnase h, probes and liquid chromatography/mass spectrometry
CA3007955A1 (en) 2015-12-10 2017-06-15 Modernatx, Inc. Lipid nanoparticles for delivery of therapeutic agents
US11096956B2 (en) 2015-12-14 2021-08-24 Stoke Therapeutics, Inc. Antisense oligomers and uses thereof
ES2882500T3 (es) 2015-12-14 2021-12-02 Cold Spring Harbor Laboratory Oligómeros antisentido para el tratamiento del síndrome de Dravet
EP3390630B1 (en) 2015-12-17 2025-01-22 ModernaTX, Inc. Polynucleotides encoding methylmalonyl-coa mutase
EP3405579A1 (en) * 2016-01-22 2018-11-28 Modernatx, Inc. Messenger ribonucleic acids for the production of intracellular binding polypeptides and methods of use thereof
KR102841205B1 (ko) 2016-02-09 2025-08-01 시버스 유에스 엘엘씨 올리고뉴클레오타이드 매개 유전자 보수를 사용한 표적화된 유전자 변형의 효율을 증가시키기 위한 방법 및 조성물
EP3423106B1 (en) 2016-03-01 2022-07-27 Alexion Pharmaceuticals, Inc. Biodegradable activated polymers for therapeutic delivery
US11318197B2 (en) 2016-03-03 2022-05-03 Duke University Compositions and methods for inducing HIV-1 antibodies
WO2017152146A2 (en) 2016-03-03 2017-09-08 Duke University Compositions and methods for inducing hiv-1 antibodies
EP3426775A1 (en) * 2016-03-10 2019-01-16 Novartis AG Chemically modified messenger rna's
ES2835051T3 (es) 2016-03-31 2021-06-21 Ethris Gmbh Secuencias de UTR mínimas novedosas
WO2017173354A2 (en) * 2016-04-01 2017-10-05 University Of Iowa Research Foundation METABOLICALLY STABILIZED DOUBLE STRANDED mRNA
EP3443001B1 (en) 2016-04-11 2025-04-30 Obsidian Therapeutics, Inc. REGULATED BIOCIRCUIT SYSTEMS
EP3443081A4 (en) 2016-04-13 2019-10-30 Duke University CRISPR / CAS9-BASED REPRESSORS FOR IN VIVO SHUT-OFF OF GEN-TARGETS AND METHOD OF USE
US20190167811A1 (en) 2016-04-13 2019-06-06 Modernatx, Inc. Lipid compositions and their uses for intratumoral polynucleotide delivery
AU2017254477A1 (en) 2016-04-18 2018-11-01 Jennifer G. ABELIN Improved HLA epitope prediction
MA45053A (fr) 2016-05-18 2019-03-27 Modernatx Inc Polynucléotides codant pour un régulateur de conductance transmembranaire de fibrose kystique pour le traitement de la fibrose kystique
US12128113B2 (en) 2016-05-18 2024-10-29 Modernatx, Inc. Polynucleotides encoding JAGGED1 for the treatment of Alagille syndrome
JP7088911B2 (ja) 2016-05-18 2022-06-21 モデルナティエックス インコーポレイテッド リラキシンをコードするポリヌクレオチド
DK3458083T5 (da) 2016-05-18 2024-10-21 Modernatx Inc Polynukleotider, der koder for interleukin-12 (il12), og anvendelser heraf
US12123030B2 (en) 2016-05-18 2024-10-22 Modernatx, Inc. Polynucleotides encoding lipoprotein lipase for the treatment of hyperlipidemia
KR102483193B1 (ko) 2016-06-03 2023-01-04 리제너론 파마슈티칼스 인코포레이티드 외인성 말단 데옥시뉴클레오타이드 전달효소를 발현하는 비인간 동물
US12385034B2 (en) 2016-06-24 2025-08-12 Modernatx, Inc. Methods and apparatus for filtration
KR101916652B1 (ko) 2016-06-29 2018-11-08 올릭스 주식회사 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도
US10927383B2 (en) 2016-06-30 2021-02-23 Ethris Gmbh Cas9 mRNAs
JP2019520829A (ja) 2016-07-07 2019-07-25 ルビウス セラピューティクス， インコーポレイテッド 外来性ｒｎａを発現する治療的細胞系に関連する組成物及び方法
EP4275747A3 (en) 2016-07-19 2024-01-24 Duke University Therapeutic applications of cpf1-based genome editing
IL308824A (en) 2016-08-17 2024-01-01 Factor Bioscience Inc Nucleic acid products and methods of administration thereof
JP6983455B2 (ja) 2016-09-14 2021-12-17 モデルナティーエックス， インコーポレイテッド 高純度ｒｎａ組成物及びその調製のための方法
WO2018067580A1 (en) 2016-10-03 2018-04-12 Duke University Methods to identify immunogens by targeting improbable mutations
FI3526323T3 (fi) 2016-10-14 2023-06-06 Prec Biosciences Inc Hepatiitti B -viruksen genomissa oleville tunnistussekvensseille spesifisiä muokattuja meganukleaaseja
AU2017345766A1 (en) 2016-10-21 2019-05-16 Modernatx, Inc. Human cytomegalovirus vaccine
JP7204643B2 (ja) 2016-10-24 2023-01-16 オリオニス バイオサイエンシズ ビーブイ 標的変異インターフェロン－ガンマおよびその使用
US12491261B2 (en) 2016-10-26 2025-12-09 Acuitas Therapeutics, Inc. Lipid nanoparticle formulations
EP3532097A1 (en) 2016-10-27 2019-09-04 The Trustees Of The University Of Pennsylvania Nucleoside-modified rna for inducing an adaptive immune response
WO2018081788A1 (en) 2016-10-31 2018-05-03 Cornell University Methods of enhancing translation ability and stability of rna molecules, treatments, and kits
MX2019005470A (es) 2016-11-10 2019-11-21 Translate Bio Inc Formulación de nanopartículas lipídicas basadas en ice mejorada para el suministro de arnm.
CN110167587A (zh) 2016-11-11 2019-08-23 摩登纳特斯有限公司 流感疫苗
EP3555289A1 (en) 2016-12-13 2019-10-23 ModernaTX, Inc. Rna affinity purification
BR112019014314A2 (pt) 2017-01-11 2020-02-18 The Trustees Of The University Of Pennsylvania Composição, e, método de indução de uma resposta imune adaptativa contra vírus zika.
EP3568158A4 (en) 2017-01-11 2020-11-18 The Board of Trustees of the Leland Stanford Junior University R-SPONDIN SUBSTITUTION MOLECULES (RSPO)
US11549149B2 (en) 2017-01-24 2023-01-10 The Broad Institute, Inc. Compositions and methods for detecting a mutant variant of a polynucleotide
WO2018140821A1 (en) 2017-01-26 2018-08-02 Surrozen, Inc. Tissue-specific wnt signal enhancing molecules and uses thereof
EP3576780A1 (en) 2017-02-01 2019-12-11 Modernatx, Inc. Immunomodulatory therapeutic mrna compositions encoding activating oncogene mutation peptides
MX2019009255A (es) 2017-02-06 2019-11-05 Orionis Biosciences Nv Proteínas quiméricas dirigidas y sus usos.
CN110573172A (zh) 2017-02-06 2019-12-13 奥里尼斯生物科学有限公司 靶向的工程化干扰素及其用途
EP3580339A4 (en) 2017-02-10 2020-12-23 Research & Business Foundation Sungkyunkwan University LONG DOUBLE STRAND RNA FOR RNA INTERFERENCE
WO2018157153A1 (en) 2017-02-27 2018-08-30 Translate Bio, Inc. Large scale synthesis of messenger rna
AU2018224326B2 (en) 2017-02-27 2024-01-04 Translate Bio, Inc. Novel codon-optimized CFTR mRNA
US11407800B2 (en) 2017-02-28 2022-08-09 Arcturus Therapeutics, Inc. Translatable molecules and synthesis thereof
TW202428301A (zh) 2017-02-28 2024-07-16 法商賽諾菲公司 治療性rna
CN110913954A (zh) 2017-03-03 2020-03-24 黑曜石疗法公司 免疫疗法的组合物和方法
CN110831961B (zh) 2017-03-03 2024-01-02 黑曜石疗法公司 用于免疫疗法的cd19组合物和方法
MA47787A (fr) 2017-03-15 2020-01-22 Modernatx Inc Vaccin contre le virus respiratoire syncytial
WO2018170270A1 (en) 2017-03-15 2018-09-20 Modernatx, Inc. Varicella zoster virus (vzv) vaccine
WO2018170245A1 (en) 2017-03-15 2018-09-20 Modernatx, Inc. Broad spectrum influenza virus vaccine
US11752206B2 (en) 2017-03-15 2023-09-12 Modernatx, Inc. Herpes simplex virus vaccine
WO2018170347A1 (en) 2017-03-17 2018-09-20 Modernatx, Inc. Zoonotic disease rna vaccines
WO2018187590A1 (en) 2017-04-05 2018-10-11 Modernatx, Inc. Reduction or elimination of immune responses to non-intravenous, e.g., subcutaneously administered therapeutic proteins
WO2018188730A1 (en) 2017-04-11 2018-10-18 Biontech Rna Pharmaceuticals Gmbh Rna for treatment of autoimmune diseases
WO2018191657A1 (en) 2017-04-13 2018-10-18 Acuitas Therapeutics, Inc. Lipids for delivery of active agents
CA3061326A1 (en) 2017-04-27 2018-11-01 The Johns Hopkins University Nucleoside-modified mrna-lipid nanoparticle lineage vaccine for hepatitis c virus
ES2981244T3 (es) 2017-04-28 2024-10-07 Acuitas Therapeutics Inc Novedosas formulaciones de nanopartículas de lípidos de carbonilo y lípidos para la administración de ácidos nucleicos
TW201907937A (zh) 2017-05-08 2019-03-01 美商葛利史東腫瘤科技公司 阿爾法病毒新抗原載體
MX2019013752A (es) 2017-05-16 2020-07-20 Translate Bio Inc Tratamiento de la fibrosis quística mediante el suministro de arnm que codifica cftr optimizado en codones.
US11377643B2 (en) 2017-05-31 2022-07-05 Ultragenyx Pharmaceutical Inc. Therapeutics for glycogen storage disease type III
ES3065816T3 (en) 2017-06-07 2026-05-08 Regeneron Pharma Compositions and methods for internalizing enzymes
WO2018224166A1 (en) 2017-06-09 2018-12-13 Biontech Rna Pharmaceuticals Gmbh Methods for predicting the usefulness of disease specific amino acid modifications for immunotherapy
EP3638292A1 (en) * 2017-06-14 2020-04-22 ModernaTX, Inc. Polynucleotides encoding coagulation factor viii
US20200131498A1 (en) 2017-06-14 2020-04-30 Modernatx, Inc. Polynucleotides encoding methylmalonyl-coa mutase
JOP20190269A1 (ar) 2017-06-15 2019-11-20 Voyager Therapeutics Inc بولي نوكليوتيدات aadc لعلاج مرض باركنسون
WO2018232357A1 (en) 2017-06-15 2018-12-20 Modernatx, Inc. Rna formulations
US10034951B1 (en) 2017-06-21 2018-07-31 New England Biolabs, Inc. Use of thermostable RNA polymerases to produce RNAs having reduced immunogenicity
BR112019028280A2 (pt) 2017-07-04 2020-07-14 Curevac Ag moléculas de ácido nucleico
WO2019010304A1 (en) * 2017-07-05 2019-01-10 Wisconsin Alumni Research Foundation MICROPARTICLES COATED WITH MINERALS FOR GENES ADMINISTRATION IN CHRONIC WOUND THERAPY
US20200165593A1 (en) 2017-07-21 2020-05-28 Modernatx, Inc. Modified mRNA Encoding a Propionyl-CoA Carboxylase and Uses Thereof
US20200179494A1 (en) 2017-07-24 2020-06-11 Modernatx, Inc. Modified mRNA Encoding a Glucose 6 Phosphatase and Uses Thereof
US11639329B2 (en) 2017-08-16 2023-05-02 Acuitas Therapeutics, Inc. Lipids for use in lipid nanoparticle formulations
EP4501322A3 (en) 2017-08-17 2025-04-16 Acuitas Therapeutics, Inc. Lipids for use in lipid nanoparticle formulations
WO2019036030A1 (en) 2017-08-17 2019-02-21 Acuitas Therapeutics, Inc. LIPIDS FOR USE IN LIPID NANOPARTICLE FORMULATIONS
US11542225B2 (en) 2017-08-17 2023-01-03 Acuitas Therapeutics, Inc. Lipids for use in lipid nanoparticle formulations
AU2018316811B2 (en) 2017-08-17 2023-07-13 The Trustees Of The University Of Pennsylvania Modified mRNA vaccines encoding herpes simplex virus glycoproteins and uses thereof
CN111212905A (zh) 2017-08-18 2020-05-29 摩登纳特斯有限公司 Rna聚合酶变体
WO2019036683A1 (en) 2017-08-18 2019-02-21 Modernatx, Inc. ANALYTICAL METHODS BY HPLC
WO2019036685A1 (en) 2017-08-18 2019-02-21 Modernatx, Inc. METHODS FOR HPLC ANALYSIS
SI3673080T1 (sl) 2017-08-25 2024-03-29 Stoke Therapeutics, Inc. Protismiselni oligomeri za zdravljenje bolezenskih stanj in bolezni
WO2019046809A1 (en) 2017-08-31 2019-03-07 Modernatx, Inc. METHODS OF MANUFACTURING LIPID NANOPARTICLES
US10653767B2 (en) 2017-09-14 2020-05-19 Modernatx, Inc. Zika virus MRNA vaccines
US11773144B2 (en) 2017-10-02 2023-10-03 Duke University Mosaic HIV-1 envelopes to induce ADCC responses
US20210180053A1 (en) 2017-11-01 2021-06-17 Novartis Ag Synthetic rnas and methods of use
EP3714048B1 (en) 2017-11-22 2025-04-09 ModernaTX, Inc. Polynucleotides encoding ornithine transcarbamylase for the treatment of urea cycle disorders
WO2019104160A2 (en) 2017-11-22 2019-05-31 Modernatx, Inc. Polynucleotides encoding phenylalanine hydroxylase for the treatment of phenylketonuria
EP3724355A1 (en) 2017-12-15 2020-10-21 Novartis AG Polya tail length analysis of rna by mass spectrometry
JP7653013B2 (ja) 2018-01-04 2025-03-28 アイコニック セラピューティクス リミテッド ライアビリティ カンパニー 抗組織因子抗体、抗体薬物コンジュゲート、及び関連する方法
CN111819285B (zh) 2018-01-09 2024-08-09 希博斯美国有限公司 防碎基因和突变
US12509492B2 (en) 2018-01-19 2025-12-30 Duke University Genome engineering with CRISPR-Cas systems in eukaryotes
WO2019148089A1 (en) 2018-01-26 2019-08-01 Orionis Biosciences Inc. Xcr1 binding agents and uses thereof
WO2019148101A1 (en) 2018-01-29 2019-08-01 Modernatx, Inc. Rsv rna vaccines
CN112074267B (zh) 2018-02-05 2024-06-28 奥里尼斯生物科学公司股份有限公司 成纤维细胞结合剂及其用途
CN112040985A (zh) 2018-02-07 2020-12-04 瑞泽恩制药公司 用于递送治疗性蛋白质的方法和组合物
EP3752610B1 (en) 2018-02-13 2026-01-28 ethris GmbH Polyribonucleotide containing deuterated nucleotides
CN112154210A (zh) * 2018-03-13 2020-12-29 利兰斯坦福初级大学董事会 用于逆转细胞老化的瞬时细胞重编程
AU2019247403B2 (en) 2018-04-04 2025-04-10 Cibus Europe, B.V. FAD2 genes and mutations
TW201945388A (zh) 2018-04-12 2019-12-01 美商精密生物科學公司 對b型肝炎病毒基因體中之識別序列具有特異性之最佳化之經工程化巨核酸酶
JP7304888B2 (ja) 2018-04-12 2023-07-07 プレシジョン バイオサイエンシズ，インク． ヒトｔ細胞受容体アルファ定常領域遺伝子に特異性を有する最適化された操作されたヌクレアーゼ
BR112020021054A2 (pt) 2018-04-25 2021-02-17 Ethris Gmbh composição, processo para a preparação de uma composição, e, composições sólida e para uso
WO2019213525A1 (en) 2018-05-04 2019-11-07 Stoke Therapeutics, Inc. Methods and compositions for treatment of cholesteryl ester storage disease
WO2019217294A1 (en) 2018-05-06 2019-11-14 Emendobio Inc. Differential knockout of an allele of a heterozygous elane gene
EP3794126A1 (en) 2018-05-15 2021-03-24 Voyager Therapeutics, Inc. Compositions and methods for the treatment of parkinson's disease
BR112020023145A2 (pt) 2018-05-17 2021-02-02 Regeneron Pharmaceuticals, Inc. anticorpo anti-cd63 ou fragmento de ligação ao antígeno do mesmo, molécula de ligação ao antígeno biespecífica, proteína terapêutica de múltiplos domínios, polinucleotídeo composição farmacêutica, e, composto
US20220403001A1 (en) 2018-06-12 2022-12-22 Obsidian Therapeutics, Inc. Pde5 derived regulatory constructs and methods of use in immunotherapy
CN108956566B (zh) * 2018-07-06 2020-10-02 军事科学院军事医学研究院环境医学与作业医学研究所 基于切刻内切酶和杂交链式反应双重放大的上转换荧光检测多氯联苯试剂盒及检测方法
EP3820499A4 (en) 2018-07-09 2022-07-13 Surrozen Operating, Inc. TISSUE SPECIFIC WNT SIGNAL ENHANCEMENT MOLECULES AND USES
CN118421617A (zh) 2018-08-24 2024-08-02 川斯勒佰尔公司 用于纯化信使rna的方法
EP3849595B1 (en) * 2018-09-13 2025-11-19 ModernaTX, Inc. Polynucleotides encoding glucose-6-phosphatase for the treatment of glycogen storage disease
AU2019338557A1 (en) * 2018-09-13 2021-03-25 Modernatx, Inc. Modified mRNA for the treatment of progressive familial intrahepatic cholestasis disorders
US12151029B2 (en) 2018-09-19 2024-11-26 Modernatx, Inc. PEG lipids and uses thereof
AU2019345067A1 (en) 2018-09-19 2021-04-08 Modernatx, Inc. High-purity peg lipids and uses thereof
WO2020061457A1 (en) 2018-09-20 2020-03-26 Modernatx, Inc. Preparation of lipid nanoparticles and methods of administration thereof
IL281615B2 (en) 2018-09-21 2026-01-01 Acuitas Therapeutics Inc Systems and methods for producing lipid nanoparticles and liposomes
EP3856233A1 (en) * 2018-09-27 2021-08-04 Modernatx, Inc. Polynucleotides encoding arginase 1 for the treatment of arginase deficiency
CN113383010B (zh) 2018-09-28 2025-09-09 沃雅戈治疗公司 具有经工程化改造的启动子的共济蛋白表达构建体及其使用方法
EP3860650A4 (en) 2018-10-01 2022-06-29 Duke University Hiv-1 envelope stabilizing mutations
WO2020072700A1 (en) 2018-10-02 2020-04-09 Dana-Farber Cancer Institute, Inc. Hla single allele lines
US12583816B2 (en) 2018-10-18 2026-03-24 Acuitas Therapeutics, Inc. Lipids for lipid nanoparticle delivery of active agents
WO2020086742A1 (en) 2018-10-24 2020-04-30 Obsidian Therapeutics, Inc. Er tunable protein regulation
EP3883592A1 (en) 2018-11-21 2021-09-29 Translate Bio, Inc. Treatment of cystic fibrosis by delivery of nebulized mrna encoding cftr
PL3891274T3 (pl) 2018-12-06 2024-03-25 Arcturus Therapeutics, Inc. Kompozycje i sposoby leczenia niedoboru transkarbamylazy ornityny
CN111303283A (zh) 2018-12-12 2020-06-19 上海君实生物医药科技股份有限公司 抗il-17a抗体及其应用
US20220062394A1 (en) 2018-12-17 2022-03-03 The Broad Institute, Inc. Methods for identifying neoantigens
US20220090047A1 (en) 2018-12-21 2022-03-24 Precision Biosciences, Inc. Genetic modification of the hydroxyacid oxidase 1 gene for treatment of primary hyperoxaluria
JP7523449B2 (ja) 2019-01-11 2024-07-26 アクイタス セラピューティクス インコーポレイテッド 活性剤の脂質ナノ粒子送達のための脂質
WO2020163379A1 (en) 2019-02-05 2020-08-13 Emendobio Inc. Crispr compositions and methods for promoting gene editing of ribosomal protein s19 (rps19) gene
WO2020168466A1 (en) 2019-02-19 2020-08-27 Stemirna Therapeutics Co., Ltd. Modified nucleoside and synthetic methods thereof
US11851694B1 (en) 2019-02-20 2023-12-26 Modernatx, Inc. High fidelity in vitro transcription
JP2022521094A (ja) 2019-02-20 2022-04-05 モデルナティエックス インコーポレイテッド 共転写キャッピング用ｒｎａポリメラーゼバリアント
KR20210134003A (ko) 2019-02-27 2021-11-08 스톡 테라퓨틱스, 인크. 병태 및 질환의 치료를 위한 안티센스 올리고머
CN113874502A (zh) 2019-03-11 2021-12-31 摩登纳特斯有限公司 补料分批体外转录方法
WO2020190750A1 (en) 2019-03-15 2020-09-24 Modernatx, Inc. Hiv rna vaccines
EP3946466A2 (en) * 2019-03-25 2022-02-09 Flagship Pioneering Innovations VI, LLC Compositions comprising modified circular polyribonucleotides and uses thereof
JP7773372B2 (ja) 2019-03-28 2025-11-19 オリオニス バイオサイエンシズ，インコーポレイテッド 線維芽細胞活性化タンパク質結合物質およびその使用
WO2020206248A1 (en) 2019-04-03 2020-10-08 Precision Biosciences, Inc. Genetically-modified immune cells comprising a microrna-adapted shrna (shrnamir)
US20220204994A1 (en) 2019-04-05 2022-06-30 Precision Biosciences, Inc. Methods of preparing populations of genetically-modified immune cells
WO2020231702A1 (en) * 2019-05-11 2020-11-19 Youngsuk Yi Compositions and methods containing exosomes
MX2021014525A (es) 2019-05-30 2022-03-17 Gritstone Bio Inc Adenovirus modificados.
JP7699552B2 (ja) 2019-07-03 2025-06-27 ファクター バイオサイエンス インコーポレイテッド カチオン性脂質及びその使用
WO2021008523A1 (zh) 2019-07-15 2021-01-21 上海君实生物医药科技股份有限公司 抗tigit抗体及其应用
WO2021016608A1 (en) 2019-07-25 2021-01-28 Precision Biosciences, Inc. Compositions and methods for sequential stacking of nucleic acid sequences into a genomic locus
US10501404B1 (en) 2019-07-30 2019-12-10 Factor Bioscience Inc. Cationic lipids and transfection methods
US11926817B2 (en) 2019-08-09 2024-03-12 Nutcracker Therapeutics, Inc. Microfluidic apparatus and methods of use thereof
CN112390838A (zh) * 2019-08-14 2021-02-23 斯微(上海)生物科技有限公司 一种改性核苷及其合成方法
JP2022544412A (ja) * 2019-08-14 2022-10-18 キュアバック アーゲー 免疫賦活特性が減少したｒｎａ組み合わせおよび組成物
DE102019122014A1 (de) 2019-08-15 2021-02-18 Technische Universität Darmstadt Reduktion der Knochenresorption, insbesondere bei chronischen Gelenkerkrankungen
AU2020333851A1 (en) 2019-08-20 2022-03-31 Precision Biosciences, Inc. Lymphodepletion dosing regimens for cellular immunotherapies
US12570725B2 (en) 2019-09-13 2026-03-10 Duke University ZIKA antibodies and their use
WO2021055609A1 (en) 2019-09-20 2021-03-25 Translate Bio, Inc. Mrna encoding engineered cftr
US12394502B2 (en) 2019-10-02 2025-08-19 The General Hospital Corporation Method for predicting HLA-binding peptides using protein structural features
JP7650873B2 (ja) 2019-10-09 2025-03-25 トランスレイト バイオ， インコーポレイテッド メッセンジャーｒｎａの組成物、方法および使用
US20210145860A1 (en) 2019-10-21 2021-05-20 Translate Bio, Inc. Compositions, methods and uses of messenger rna
WO2021081437A2 (en) 2019-10-23 2021-04-29 Duke University Compositions comprising v2 opt hiv envelopes
WO2021079002A2 (en) 2019-10-24 2021-04-29 Novago Therapeutics Ag Novel anti-nogo-a antibodies
WO2021087305A1 (en) 2019-10-30 2021-05-06 Precision Biosciences, Inc. Cd20 chimeric antigen receptors and methods of use for immunotherapy
EP4054652A4 (en) 2019-11-07 2023-11-22 Icahn School of Medicine at Mount Sinai SYNTHETIC MODIFIED RNA AND ITS USES
EP4069285A1 (en) 2019-12-06 2022-10-12 Precision BioSciences, Inc. Methods for cancer immunotherapy, using lymphodepletion regimens and cd19, cd20 or bcma allogeneic car t cells
ES3022990T3 (en) 2019-12-06 2025-05-29 Prec Biosciences Inc Optimized engineered meganucleases having specificity for a recognition sequence in the hepatitis b virus genome
KR20220142432A (ko) 2019-12-20 2022-10-21 트랜슬레이트 바이오 인코포레이티드 메신저 rna의 직장 전달
US12053551B2 (en) 2019-12-20 2024-08-06 Translate Bio, Inc. Process of preparing mRNA-loaded lipid nanoparticles
MX2022007905A (es) 2019-12-31 2022-08-25 Elixirgen Therapeutics Inc Administracion transitoria basada en temperatura de acidos nucleicos y proteinas a celulas y tejidos.
WO2021142245A1 (en) 2020-01-10 2021-07-15 Translate Bio, Inc. Compounds, pharmaceutical compositions and methods for modulating expression of muc5b in lung cells and tissues
US12194089B2 (en) 2020-02-04 2025-01-14 CureVac SE Coronavirus vaccine
AU2021218671A1 (en) 2020-02-10 2022-10-06 Translate Bio, Inc. Methods and compositions for messenger RNA purification
MX2022010117A (es) 2020-02-18 2022-11-14 Translate Bio Inc Procesos mejorados para la transcripción in vitro del arn mensajero.
WO2021169932A1 (zh) 2020-02-24 2021-09-02 中国科学院微生物研究所 新型冠状病毒的人源单克隆抗体及其应用
WO2021173840A1 (en) 2020-02-25 2021-09-02 Translate Bio, Inc. Improved processes of preparing mrna-loaded lipid nanoparticles
WO2021178510A1 (en) 2020-03-03 2021-09-10 Arcturus Therapeutics, Inc. Compositions and methods for the treatment of ornithine transcarbamylase deficiency
US12194157B2 (en) 2020-04-09 2025-01-14 Finncure Oy Carrier for targeted delivery to a host
AU2021252164A1 (en) 2020-04-09 2022-12-15 Finncure Oy Mimetic nanoparticles for preventing the spreading and lowering the infection rate of novel coronaviruses
CN113521269A (zh) 2020-04-22 2021-10-22 生物技术Rna制药有限公司 冠状病毒疫苗
EP4146680A1 (en) 2020-05-07 2023-03-15 Translate Bio, Inc. Composition and methods for treatment of primary ciliary dyskinesia
US12605399B2 (en) 2020-05-07 2026-04-21 Translate Bio, Inc. Compositions for CFTR MRNA therapy
WO2021226436A1 (en) 2020-05-07 2021-11-11 Translate Bio, Inc. Optimized nucleotide sequences encoding sars-cov-2 antigens
IL297948A (en) 2020-05-07 2023-01-01 Translate Bio Inc Production of optimal nucleotide sequences
BR112022022889A2 (pt) 2020-05-11 2023-04-04 Stoke Therapeutics Inc Oligômeros antissentido de opa1 para tratamento de condições e doenças
WO2021231259A1 (en) 2020-05-11 2021-11-18 Precision Biosciences, Inc. Self-limiting viral vectors encoding nucleases
US12595469B2 (en) 2020-05-12 2026-04-07 Precision Biosciences, Inc. Treatment of retinitis pigmentosa using improved engineered meganucleases
EP4149425A1 (en) 2020-05-15 2023-03-22 Translate Bio, Inc. Lipid nanoparticle formulations for mrna delivery
CA3178965A1 (en) 2020-05-15 2021-11-18 Christian COBAUGH Messenger rna encoding cas9 for use in genome-editing systems
WO2021245184A1 (en) 2020-06-02 2021-12-09 Neurimmune Ag HUMAN ANTIBODIES AGAINST SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS-2 (SARS-CoV-2)
EP4179112A4 (en) 2020-07-13 2024-11-20 The Board of Trustees of the Leland Stanford Junior University Systems and methods to assess rna stability
CN116096416B (zh) 2020-07-13 2026-02-03 上海君实生物医药科技股份有限公司 抗cldn-18.2抗体及其用途
JP7798855B2 (ja) 2020-07-16 2026-01-14 アクイタス セラピューティクス インコーポレイテッド 脂質ナノ粒子に使用するためのカチオン性脂質
BR112023000826A2 (pt) 2020-07-21 2023-02-07 Shanghai Junshi Biosciences Co Ltd Anticorpo anti-ctla-4 e uso do mesmo
JP2023536627A (ja) 2020-08-05 2023-08-28 ドラゴンフライ セラピューティクス， インコーポレイテッド Ｅｇｆｒを標的とする抗体およびその使用
EP4192496A4 (en) 2020-08-06 2025-01-01 Gritstone bio, Inc. MULTIEPITOP VACCINE CASSETTES
US20230279408A1 (en) * 2020-08-07 2023-09-07 The Hong Kong University Of Science And Technology Compositions and methods for increasing protein expression
US20260028412A1 (en) 2020-08-10 2026-01-29 Precision Biosciences, Inc. Antibodies and fragments specific for b-cell maturation antigen and uses thereof
WO2022040582A1 (en) 2020-08-21 2022-02-24 Precision Biosciences, Inc. Engineered meganucleases having specificity for a recognition sequence in the transthyretin gene
US11406703B2 (en) 2020-08-25 2022-08-09 Modernatx, Inc. Human cytomegalovirus vaccine
EP4204015A4 (en) 2020-08-31 2025-01-01 The Board of Trustees of the Leland Stanford Junior University Systems and methods for producing rna constructs with increased translation and stability
US12419948B2 (en) 2020-08-31 2025-09-23 The Broad Institute, Inc. Immunogenic compositions and use thereof
US20250188154A1 (en) * 2020-09-15 2025-06-12 Duke University Coronavirus antibodies and uses thereof
WO2022076562A1 (en) 2020-10-06 2022-04-14 Translate Bio, Inc. Improved process and formulation of lipid nanoparticles
WO2022076547A1 (en) 2020-10-07 2022-04-14 Precision Biosciences, Inc. Lipid nanoparticle compositions
US20220110884A1 (en) 2020-10-12 2022-04-14 Translate Bio, Inc. Process of preparing mrna-loaded lipid nanoparticles
US20220133631A1 (en) 2020-10-12 2022-05-05 Translate Bio, Inc. Process of preparing ice-based lipid nanoparticles
IL302064A (en) * 2020-10-13 2023-06-01 Univ Pennsylvania Targeting intracorporeal CD4-positive t cells for messenger RNA therapies
KR20230118715A (ko) 2020-10-14 2023-08-11 조지 메이슨 리서치 파운데이션 인코포레이티드 이온화 가능 지질 및 이의 제조 및 사용 방법
JP2023545503A (ja) 2020-10-15 2023-10-30 トランスレイト バイオ， インコーポレイテッド メッセンジャーｒｎａの大規模合成
WO2022090752A1 (en) 2020-10-26 2022-05-05 Pécsi Tudományegyetem Vaccine platform
AU2021373892A1 (en) 2020-11-09 2023-07-06 Translate Bio, Inc. Improved compositions for delivery of codon-optimized mrna
GB202017649D0 (en) 2020-11-09 2020-12-23 Autolus Ltd Polypeptide
IL302733B2 (en) 2020-11-12 2025-05-01 Prec Biosciences Inc Engineered nucleases with specificity for recognition sequences in the dystrophin gene
CA3198268A1 (en) 2020-11-16 2022-05-19 Surrozen Operating, Inc. Liver-specific wnt signal enhancing molecules and uses thereof
WO2022106860A1 (en) 2020-11-20 2022-05-27 Pécsi Tudományegyetem Recombinant peptides for use in therapy
CA3200234A1 (en) 2020-11-25 2022-06-02 Daryl C. Drummond Lipid nanoparticles for delivery of nucleic acids, and related methods of use
CN116723829A (zh) 2020-11-25 2023-09-08 翻译生物公司 稳定的液体脂质纳米颗粒配制品
PE20231178A1 (es) 2020-12-03 2023-08-01 Scribe Therapeutics Inc Sistemas crispr tipo v clase 2 disenados por ingenieria
US20240156946A1 (en) 2020-12-22 2024-05-16 CureVac SE Rna vaccine against sars-cov-2 variants
US20240299585A1 (en) 2021-01-08 2024-09-12 Precision Biosciences, Inc. Engineered meganucleases having specificity for a recognition sequence in the hydroxyacid oxidase 1 gene
WO2022150717A1 (en) 2021-01-11 2022-07-14 Modernatx, Inc. Seasonal rna influenza virus vaccines
JP2024504614A (ja) 2021-01-14 2024-02-01 トランスレイト バイオ， インコーポレイテッド ｍＲＮＡがコードする抗体を送達する方法および組成物
EP4284823A1 (en) 2021-01-28 2023-12-06 Precision BioSciences, Inc. Modulation of tgf beta signaling in genetically-modified eukaryotic cells
EP4284335A1 (en) 2021-02-01 2023-12-06 RegenxBio Inc. Gene therapy for neuronal ceroid lipofuscinoses
US20240309087A1 (en) 2021-02-09 2024-09-19 Shanghai Junshi Biosciences Co., Ltd. Anti-cd112r antibody and use thereof
WO2022177597A1 (en) * 2021-02-16 2022-08-25 The Board Of Trustees Of The Leland Stanford Junior University Systems and methods to enhance rna stability and translation and uses thereof
AU2022229740A1 (en) 2021-03-01 2023-08-24 New York Society For The Relief Of The Ruptured And Crippled, Maintaining The Hospital For Special Surgery Humanized antibodies against irhom2
US20220323553A1 (en) * 2021-03-08 2022-10-13 The Trustees Of The University Of Pennsylvania Epigenomic editing and reactivation of targets for the treatment of Fragile X syndrome
WO2022204219A1 (en) 2021-03-22 2022-09-29 Recode Therapeutics, Inc. Compositions and methods for targeted delivery to cells
WO2022204549A1 (en) 2021-03-25 2022-09-29 Translate Bio, Inc. Optimized nucleotide sequences encoding the extracellular domain of human ace2 protein or a portion thereof
WO2022207652A1 (en) 2021-03-29 2022-10-06 Scirhom Gmbh Methods of treatment using protein binders to irhom2 epitopes
WO2022214664A1 (en) 2021-04-09 2022-10-13 Philogen S.P.A. Improved interferon-gamma mutant
WO2022225918A1 (en) 2021-04-19 2022-10-27 Translate Bio, Inc. Improved compositions for delivery of mrna
JP2024517655A (ja) 2021-04-22 2024-04-23 プレシジョン バイオサイエンシズ，インク． ヒトのミトコンドリアゲノムを標的とする操作されたメガヌクレアーゼ
EP4736838A2 (en) 2021-04-22 2026-05-06 Precision Biosciences, Inc. Engineered meganucleases that target human mitochondrial genomes
KR20240004662A (ko) 2021-04-29 2024-01-11 트랜슬레이트 바이오 인코포레이티드 폴리 a 테일 길이를 측정하는 방법
CA3217115A1 (en) * 2021-04-30 2022-11-03 The Trustees Of The University Of Pennsylvania Compositions and methods for targeting lipid nanoparticle therapeutics to stem cells
WO2022234003A1 (en) 2021-05-07 2022-11-10 Avacta Life Sciences Limited Cd33 binding polypeptides with stefin a protein
WO2022235838A1 (en) 2021-05-07 2022-11-10 Helix Nanotechnologies, Inc. Modified ribonucleic acids and uses thereof
US20220363937A1 (en) 2021-05-14 2022-11-17 Armstrong World Industries, Inc. Stabilization of antimicrobial coatings
EP4351623A1 (en) 2021-06-09 2024-04-17 Icahn School of Medicine at Mount Sinai Gene combination as a broad spectrum antiviral
AU2022301302A1 (en) 2021-07-01 2024-01-25 Indapta Therapeutics, Inc. Engineered natural killer (nk) cells and related methods
JP2024527541A (ja) 2021-07-01 2024-07-25 トランスレイト バイオ， インコーポレイテッド Ｍｒｎａの送達のための組成物
WO2023010135A1 (en) 2021-07-30 2023-02-02 Tune Therapeutics, Inc. Compositions and methods for modulating expression of methyl-cpg binding protein 2 (mecp2)
EP4377459A2 (en) 2021-07-30 2024-06-05 Tune Therapeutics, Inc. Compositions and methods for modulating expression of frataxin (fxn)
WO2023023487A1 (en) 2021-08-16 2023-02-23 Translate Bio, Inc. Screening codon-optimized nucleotide sequences
WO2023023589A2 (en) 2021-08-18 2023-02-23 The Trustees Of The University Of Pennsylvania Mrna vaccines against tick salivary proteins, and methods of using same
EP4393515A1 (en) 2021-08-26 2024-07-03 Shanghai Junshi Biosciences Co., Ltd. Anti-cldn-18.2 antibody-drug conjugate and use thereof
EP4412711A1 (en) 2021-10-07 2024-08-14 Avacta Life Sciences Limited Serum half-life extended pd-l1 binding polypeptides
TW202334196A (zh) 2021-10-07 2023-09-01 英商阿法克塔生命科學有限公司 Pd-l1結合多肽
EP4419660A2 (en) 2021-10-19 2024-08-28 Precision BioSciences, Inc. Gene editing methods for treating alpha-1 antitrypsin (aat) deficiency
US20240408235A1 (en) 2021-10-19 2024-12-12 Precision Biosciences, Inc. Gene editing methods for treating alpha-1 antitrypsin (aat) deficiency
EP4419716A1 (en) 2021-10-21 2024-08-28 CureVac Netherlands B.V. Cancer neoantigens
EP4169578A1 (en) 2021-10-22 2023-04-26 BioNTech SE Oligosaccharide compounds and complexes
US20250057944A1 (en) 2021-10-22 2025-02-20 BioNTech SE Oligosaccharide complexes and uses
EP4285932A1 (en) 2022-05-30 2023-12-06 BioNTech SE Oligosaccharide complexes and uses
EP4402149A1 (en) 2021-10-22 2024-07-24 BioNTech SE Disulfide oligosaccharide compounds and complexes
EP4402150A1 (en) 2021-10-22 2024-07-24 BioNTech SE Oligosaccharide compounds and complexes
EP4286004A1 (en) 2022-05-30 2023-12-06 BioNTech SE Disulfide oligosaccharide compounds and complexes
WO2023067121A1 (en) 2021-10-22 2023-04-27 BioNTech SE Oligosaccharide compounds and complexes
EP4286394A1 (en) 2022-05-30 2023-12-06 BioNTech SE Oligosaccharide compounds and complexes
EP4401788A1 (en) 2021-10-22 2024-07-24 BioNTech SE Oligosaccharide complexes and uses
EP4285933A1 (en) 2022-05-30 2023-12-06 BioNTech SE Oligosaccharide complexes and uses
EP4169534A1 (en) 2021-10-22 2023-04-26 BioNTech SE Oligosaccharide complexes and uses
EP4169580A1 (en) 2021-10-22 2023-04-26 BioNTech SE Oligosaccharide compounds and complexes
EP4286003A1 (en) 2022-05-30 2023-12-06 BioNTech SE Oligosaccharide compounds and complexes
EP4186528A1 (en) 2021-11-30 2023-05-31 BioNTech SE Oligosaccharide complexes and uses
EP4169579A1 (en) 2021-10-22 2023-04-26 BioNTech SE Disulfide oligosaccharide compounds and complexes
WO2023081767A1 (en) 2021-11-05 2023-05-11 Precision Biosciences, Inc. Methods for immunotherapy
WO2023083434A1 (en) * 2021-11-09 2023-05-19 BioNTech SE Rna encoding peptidoglycan hydrolase and use thereof for treating bacterial infection
AU2022388747A1 (en) 2021-11-10 2024-06-20 Translate Bio, Inc. Composition and methods for treatment of primary ciliary dyskinesia
US12186387B2 (en) 2021-11-29 2025-01-07 BioNTech SE Coronavirus vaccine
US20230220106A1 (en) 2021-12-08 2023-07-13 Dragonfly Therapeutics, Inc. Antibodies targeting 5t4 and uses thereof
CA3242402A1 (en) 2021-12-16 2023-06-22 Acuitas Therapeutics, Inc. Lipids for use in lipid nanoparticle formulations
US12529047B1 (en) 2021-12-21 2026-01-20 Modernatx, Inc. mRNA quantification methods
EP4202045A1 (en) 2021-12-22 2023-06-28 Universität Hamburg Synthetic transfer rna with modified nucleotides
WO2023133579A1 (en) 2022-01-10 2023-07-13 Regeneron Pharmaceuticals, Inc. Bbb-targeted gaa delivered as gene therapy treats cns and muscle in pompe disease model mice
KR20240137640A (ko) 2022-01-20 2024-09-20 상하이 준스 바이오사이언스 컴퍼니 리미티드 항-cd3 및 항-cd20 이중특이성 항체 및 이의 용도
WO2023145755A1 (ja) 2022-01-25 2023-08-03 公益財団法人川崎市産業振興財団 経皮投与用のｒｎａを含む組成物および当該組成物の投与方法
EP4471056A4 (en) 2022-01-28 2026-02-18 Shanghai Junshi Biosciences Co Ltd Anti-DKK1 antibodies, pharmaceutical composition and associated uses
KR20240170822A (ko) 2022-03-24 2024-12-04 네이쳐스 툴박스 인코포레이티드 슈도우리딘 트리포스페이트의 효소적 생산을 위한 방법 및 조성물
US20250277059A1 (en) 2022-04-12 2025-09-04 Riken Antibody used to treat coronavirus infection
CN115873836B (zh) 2022-04-29 2024-01-23 武汉合生科技有限公司 一种橙花叔醇合成酶及应用
WO2023218243A1 (en) 2022-05-12 2023-11-16 Avacta Life Sciences Limited Lag-3/pd-l1 binding fusion proteins
EP4531819A2 (en) 2022-05-25 2025-04-09 Akagera Medicines, Inc. Lipid nanoparticles for delivery of nucleic acids and methods of use thereof
TW202400652A (zh) 2022-05-25 2024-01-01 大陸商映恩生物製藥（蘇州）有限公司 抗ｂｄｃａ２抗體及其用途
CN119562807A (zh) 2022-05-30 2025-03-04 生物技术公司 用于递送核酸的复合物
TW202413643A (zh) 2022-06-07 2024-04-01 美商斯奎柏治療公司 用於靶向pcsk9的組合物及方法
GB2634837A (en) 2022-06-07 2025-04-23 Scribe Therapeutics Inc Compositions and methods for the targeting of PCSK9
KR20250044484A (ko) 2022-06-24 2025-03-31 튠 쎄라퓨틱스, 인코포레이티드 표적 유전자 억제를 통해 저밀도 지단백질을 감소시키기 위한 조성물, 시스템, 및 방법
WO2024002985A1 (en) 2022-06-26 2024-01-04 BioNTech SE Coronavirus vaccine
CN120051297A (zh) 2022-06-30 2025-05-27 因达普塔治疗公司 工程化自然杀伤(nk)细胞与抗体疗法的组合及相关方法
EP4555090A1 (en) 2022-07-11 2025-05-21 Icahn School of Medicine at Mount Sinai Regulatory system for expression of a gene of interest in a target cell and method of use thereof
EP4554967A2 (en) 2022-07-12 2025-05-21 Tune Therapeutics, Inc. Compositions, systems, and methods for targeted transcriptional activation
WO2024023246A1 (en) 2022-07-28 2024-02-01 Philogen S.P.A. Antibody binding to pd1
EP4568997A1 (en) 2022-08-08 2025-06-18 ATB Therapeutics Humanized antibodies against cd79b
EP4570913A1 (en) 2022-08-11 2025-06-18 Shanghai Junshi Biosciences Co., Ltd. Anti-cgrp antibody and use
CN120435557A (zh) 2022-08-19 2025-08-05 图恩疗法股份有限公司 通过靶向基因阻遏调节乙型肝炎病毒的组合物、系统和方法
EP4356933A1 (en) 2022-09-07 2024-04-24 Eyegene, Inc. Composition for delivering modified nucleic acid-containing mrna
WO2024064642A2 (en) 2022-09-19 2024-03-28 Tune Therapeutics, Inc. Compositions, systems, and methods for modulating t cell function
US20240228652A9 (en) 2022-09-20 2024-07-11 Visterra, Inc. Treatment of complement mediated diseases and disorders with c3b antibodies
KR20250075602A (ko) 2022-09-23 2025-05-28 광저우 린톤팜 컴퍼니 리미티드 분리된 항원 결합 단백질 및 이의 용도
US20260096998A1 (en) 2022-09-26 2026-04-09 BioNTech SE Nucleic acid complexes and uses thereof
WO2024086827A2 (en) 2022-10-20 2024-04-25 Repertoire Immune Medicines, Inc. Cd8 t cell targeted il2
EP4605010A1 (en) 2022-10-21 2025-08-27 BioNTech SE Nucleic acid complexes and uses thereof
EP4608442A1 (en) 2022-10-28 2025-09-03 GlaxoSmithKline Biologicals S.A. Nucleic acid based vaccine
EP4622630A1 (en) 2022-11-21 2025-10-01 Translate Bio, Inc. Compositions of dry powder formulations of messenger rna and methods of use thereof
KR20250130296A (ko) 2022-11-22 2025-09-01 상하이 홍쳉 바이오파머수티컬 코., 엘티디. 항-ccr8 항체 및 이의 용도
WO2024126809A1 (en) 2022-12-15 2024-06-20 Sanofi Mrna encoding influenza virus-like particle
EP4637813A1 (en) 2022-12-20 2025-10-29 Sanofi Pasteur Rhinovirus mrna vaccine
CN118240032A (zh) * 2022-12-23 2024-06-25 深圳碳云智肽药物科技有限公司 一种乙肝病毒抗原多肽及其应用
WO2024133884A2 (en) 2022-12-23 2024-06-27 Sanofi Optimized tailing of messenger rna
JP2026504815A (ja) 2022-12-29 2026-02-10 ポップヴァックス プライベート リミテッド マルチターゲットワクチンおよび治療剤
WO2024141784A2 (en) 2022-12-29 2024-07-04 Popvax Private Limited Broadly protective betacoronavirus vaccines and compositions
WO2024148167A1 (en) 2023-01-05 2024-07-11 Precision Biosciences, Inc. Optimized engineered meganucleases having specificity for the human t cell receptor alpha constant region gene
WO2024151975A1 (en) 2023-01-13 2024-07-18 Igor Lednev Detecting degradation of a polynucleotide by raman spectroscopy
CN120957744A (zh) 2023-01-20 2025-11-14 阿斯利康(瑞典)有限公司 核酸分子
EP4652284A1 (en) 2023-01-20 2025-11-26 Astrazeneca AB Vaccine
AU2024213258A1 (en) 2023-01-31 2025-06-26 Seqirus Inc. Capping assay
WO2024163683A2 (en) 2023-02-01 2024-08-08 Tune Therapeutics, Inc. Systems, compositions, and methods for modulating expression of methyl-cpg binding protein 2 (mecp2) and x-inactive specific transcript (xist)
WO2024163678A2 (en) 2023-02-01 2024-08-08 Tune Therapeutics, Inc. Fusion proteins and systems for targeted activation of frataxin (fxn) and related methods
EP4667497A1 (en) 2023-02-13 2025-12-24 Shaoxing Institute, Zhejiang University Bispecific antibody and use thereof
WO2024170684A1 (en) 2023-02-15 2024-08-22 Sanofi Screening codon-optimized nucleotide sequences
CN120858173A (zh) 2023-03-07 2025-10-28 赛诺菲巴斯德有限公司 用kp34聚合酶制造信使rna
WO2024206565A1 (en) 2023-03-29 2024-10-03 Scribe Therapeutics Inc. Repressor fusion protein systems
AU2024248139A1 (en) 2023-03-29 2025-09-25 Scribe Therapeutics Inc. Compositions and methods for the targeting of pcsk9
TW202444910A (zh) 2023-03-29 2024-11-16 美商斯奎柏治療公司 編碼casx之信使rna
WO2024206676A1 (en) 2023-03-29 2024-10-03 Scribe Therapeutics Inc. Compositions and methods for the targeting of lpa
MX2025012337A (es) 2023-04-17 2026-02-03 Sanofi Pasteur Inc Formulaciones de polvo seco reconstituibles y métodos de uso de las mismas
JP2026505939A (ja) 2023-05-08 2026-02-20 メルク・シャープ・アンド・ドーム・エルエルシー ノロウイルスｖｐ１抗原をコードするポリヌクレオチドおよびその使用
AU2024279278A1 (en) 2023-05-31 2025-12-18 Capstan Therapeutics, Inc. Lipid nanoparticle formulations and compositions
US12531162B1 (en) * 2023-05-31 2026-01-20 Northeastern University Multi-dimensional phenotypic space for genotype to phenotype mapping and intelligent design of cancer drug therapies using a deep learning net
CN121311249A (zh) 2023-06-22 2026-01-09 公益财团法人川崎市产业振兴财团 提高核酸的血中稳定性、提高靶向效率的方法
WO2025006799A1 (en) 2023-06-27 2025-01-02 Capstan Therapeutics, Inc. Extracorporeal and ex vivo engineering of select cell populations from peripheral blood
EP4734960A1 (en) 2023-06-28 2026-05-06 Sanofi Pasteur Inc. Sterol analogs in lipid nanoparticle formulations
WO2025012671A1 (en) 2023-07-07 2025-01-16 Institute National De La Sante Et De La Recherche Medicale (Inserm) Sars-cov-2 5'utr sequences and linkage thereof to coding sequences
WO2025029840A1 (en) 2023-07-31 2025-02-06 Tune Therapeutics, Inc. Compositions and methods for multiplexed activation and repression of t cell gene expression
WO2025029835A1 (en) 2023-07-31 2025-02-06 Tune Therapeutics, Inc. Compositions and methods for modulating il-2 gene expression
WO2025026545A1 (en) 2023-08-01 2025-02-06 BioNTech SE Ionizable thioplipids and uses thereof
WO2025027089A1 (en) 2023-08-01 2025-02-06 BioNTech SE Ionizable thiolipids and uses thereof
IL326358A (en) 2023-08-03 2026-04-01 Univ Pennsylvania RNA compositions encoding herpes simplex virus glycoprotein E and/or glycoprotein I antigens and their uses
AU2024316992A1 (en) 2023-08-03 2026-03-12 BioNTech SE Rna compositions encoding herpes simplex virus glycoprotein b antigens and uses thereof
WO2025038494A1 (en) 2023-08-11 2025-02-20 Tune Therapeutics, Inc. Compositions, systems, and methods for lymphoid cell differentiation using targeted gene activation
WO2025059073A1 (en) 2023-09-11 2025-03-20 Tune Therapeutics, Inc. Epigenetic editing methods and systems for differentiating stem cells
WO2025059215A1 (en) 2023-09-12 2025-03-20 Aadigen, Llc Methods and compositions for treating or preventing cancer
WO2025072383A1 (en) 2023-09-25 2025-04-03 The Broad Institute, Inc. Viral open reading frames, uses thereof, and methods of detecting the same
WO2025072293A1 (en) 2023-09-27 2025-04-03 Scribe Therapeutics Inc. Optimized mrnas encoding casx proteins
IL327045A (en) 2023-10-05 2026-05-01 Capstan Therapeutics Inc Structure-restricted ionizable cationic lipids and lipid nanoparticles
WO2025076113A1 (en) 2023-10-05 2025-04-10 Capstan Therapeutics, Inc. Ionizable cationic lipids with conserved spacing and lipid nanoparticles
AU2024370741A1 (en) 2023-11-02 2026-05-07 Capstan Therapeutics, Inc. Rna for in vivo transfection with increased expression
WO2025097055A2 (en) 2023-11-02 2025-05-08 The Broad Institute, Inc. Compositions and methods of use of t cells in immunotherapy
US12562256B2 (en) * 2023-11-07 2026-02-24 New York University Systems, methods and computer-accessible medium for identifying target pairs for CAR-T therapy
WO2025101946A1 (en) 2023-11-08 2025-05-15 Precision Biosciences, Inc. Polypeptide linkers for use in engineered meganucleases
WO2025104351A1 (en) 2023-11-17 2025-05-22 Sanofi Pasteur Inc. Hplc-based assays for detecting multiple mrna constructs
WO2025124711A1 (en) 2023-12-13 2025-06-19 BioNTech SE Glycolipid compositions
US20250332281A2 (en) 2023-12-15 2025-10-30 Capstan Therapeutics, Inc. Humanized anti-cd8 antibodies and uses thereof
WO2025129158A1 (en) 2023-12-15 2025-06-19 The Broad Institute, Inc. Engineered arc delivery vesicles and uses thereof
WO2025129157A1 (en) 2023-12-15 2025-06-19 The Trustees Of The University Of Pennsylvania Gene therapy for treatment of canavan disease
WO2025133951A1 (en) 2023-12-21 2025-06-26 Genevant Sciences Gmbh Ionizable lipids suitable for lipid nanoparticles
TW202525287A (zh) 2023-12-21 2025-07-01 德商拜恩技術運輸科技有限責任公司 可離子化脂質
WO2025134066A1 (en) 2023-12-21 2025-06-26 Biontech Delivery Technologies Gmbh Ionizable lipids
WO2025144938A1 (en) 2023-12-26 2025-07-03 Emmune, Inc. Systems for nucleic acid transfer
WO2025141200A1 (en) 2023-12-29 2025-07-03 Sanofi Pasteur Inc. Modified rna polymerases
US20250302763A1 (en) 2024-02-22 2025-10-02 Capstan Therapeutics, Inc. Immune engineering amplification
WO2025184125A1 (en) 2024-02-28 2025-09-04 Korro Bio, Inc. Lambda n-based compositions and methods for nucleic acids editing
WO2025188687A1 (en) 2024-03-04 2025-09-12 Beam Therapeutics Inc. Stable rna compositions with stem loop, and methods thereof
EP4613860A1 (en) 2024-03-07 2025-09-10 Technische Universität Darmstadt Inhibitors of mir-574-5p for use in intra-articular treatment of osteoarthritis and other related arthritic diseases
WO2025194138A1 (en) 2024-03-14 2025-09-18 Tessera Therapeutics, Inc. St1cas9 compositions and methods for modulating a genome
WO2025210521A1 (en) 2024-04-04 2025-10-09 Genevant Sciences Gmbh Lipid nanoparticles for stimulating t cells
WO2025210520A1 (en) 2024-04-04 2025-10-09 Genevant Sciences Gmbh Lipid nanoparticles for inducing an immunological response
WO2025217452A1 (en) 2024-04-11 2025-10-16 Capstan Therapeutics, Inc. Constrained ionizable cationic lipids and lipid nanoparticles
WO2025217454A2 (en) 2024-04-11 2025-10-16 Capstan Therapeutics, Inc. Ionizable cationic lipids and lipid nanoparticles
WO2025231432A1 (en) * 2024-05-03 2025-11-06 Caribou Biosciences, Inc. In vivo gene editing with crispr systems
WO2025240940A1 (en) 2024-05-17 2025-11-20 Scribe Therapeutics Inc. Compositions and methods for the targeting of apolipoprotein c3
WO2025255393A1 (en) 2024-06-06 2025-12-11 The Trustees Of The University Of Pennsylvania Herpes simplex virus antigen binding agents for mitigation of herpes simplex virus associated disease
WO2025260068A1 (en) 2024-06-14 2025-12-18 Tune Therapeutics, Inc. Lipid nanoparticle formulation for delivery of nucleic acids to cells
WO2025262460A1 (en) 2024-06-21 2025-12-26 BioNTech SE Lipid compositions for nucleic acid delivery
WO2026015647A1 (en) 2024-07-09 2026-01-15 Tune Therapeutics, Inc. Compositions, systems, and methods for cell differentiation using targeted gene activation of dll4 and/or vcam1
WO2026017917A1 (en) * 2024-07-19 2026-01-22 Ethris Gmbh Rnas with reduced ribosomal frameshift expression products
WO2026022677A1 (en) 2024-07-22 2026-01-29 Genevant Sciences Gmbh Permanently charged cationic lipids
WO2026022656A2 (en) 2024-07-22 2026-01-29 Genevant Sciences Gmbh Lipid particle formulations with permanently charged cationic lipids
WO2026028165A1 (en) 2024-08-01 2026-02-05 Precision Biosciences, Inc. Engineered meganucleases having specificity for recognition sequences in the c9orf72 gene
WO2026033380A1 (en) 2024-08-05 2026-02-12 BioNTech SE Process for preparing oligosaccharide complexes
WO2026033123A1 (en) 2024-08-08 2026-02-12 Sanofi Pasteur Inc. Lipid nanoparticle formulations for mrna delivery
WO2026041734A1 (en) 2024-08-22 2026-02-26 Novago Therapeutics Ag Methods for treating neurological disorders using anti-nogo-a antibodies
WO2026064753A1 (en) 2024-09-23 2026-03-26 Tune Therapeutics, Inc. Dna methyltransferase-like protein (dnmt3l) or dna methyltransferase 3a (dnmt3a) repressor systems for epigenetic editing
WO2026078579A1 (en) 2024-10-08 2026-04-16 Precision Biosciences, Inc. Methods and compositions for treating hepatitis b virus-related conditions
WO2026083241A1 (en) 2024-10-15 2026-04-23 Genevant Sciences Gmbh Ionizable lipids comprising n,n-substituted hydroxylamine esters
WO2026085437A1 (en) 2024-10-18 2026-04-23 Health Research, Inc. Lyme disease vaccine and method of use thereof
WO2026083328A1 (en) 2024-10-18 2026-04-23 Precision Biosciences, Inc. Base editing nucleotide sequences using homology directed repair
WO2026083329A1 (en) 2024-10-18 2026-04-23 Precision Biosciences, Inc. Methods of nuclease-initiated homology directed repair and replacement and compositions and uses thereof
WO2026093322A1 (en) 2024-10-28 2026-05-07 Sanofi Pasteur Inc. Improved dna constructs for manufacturing messenger rna by in vitro transcription

Family Cites Families (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5807718A (en) 1994-12-02 1998-09-15 The Scripps Research Institute Enzymatic DNA molecules
WO1996017954A1 (en) * 1994-12-08 1996-06-13 Pabio Chemical labelling of objects
AU4412096A (en) * 1994-12-13 1996-07-03 Ribozyme Pharmaceuticals, Inc. Method and reagent for treatment of arthritic conditions, induction of graft tolerance and reversal of immune responses
US5824497A (en) 1995-02-10 1998-10-20 Mcmaster University High efficiency translation of mRNA molecules
WO1999014346A2 (en) * 1997-09-19 1999-03-25 Sequitur, Inc. SENSE mRNA THERAPY
US6127535A (en) * 1997-11-05 2000-10-03 Ribozyme Pharmaceuticals, Inc. Nucleoside triphosphates and their incorporation into oligonucleotides
WO1999033982A2 (en) 1997-12-23 1999-07-08 Chiron Corporation Human genes and gene expression products i
US6066625A (en) 1998-02-03 2000-05-23 Methylgene, Inc. Optimized antisense oligonucleotides complementary to DNA methyltransferase sequences
WO2000027340A2 (en) * 1998-11-12 2000-05-18 The Children's Medical Center Corporation USE OF t-RNA AND FRAGMENTS FOR INHIBITING ANGIOGENESIS AND COMPOSITIONS THEREOF
WO2001002608A1 (en) * 1999-07-06 2001-01-11 Isis Pharmaceuticals, Inc. Oligonucleotides incorporating both 2-aminoadenine and 5-substituted pyrimidines
US20040086880A1 (en) * 1999-07-20 2004-05-06 Sampson Jeffrey R Method of producing nucleic acid molecules with reduced secondary structure
US20040229271A1 (en) * 2000-05-19 2004-11-18 Williams Richard B. Compositions and methods for the identification and selection of nucleic acids and polypeptides
WO2005072087A2 (en) * 2003-12-12 2005-08-11 Proteonova, Inc. System and methods for nucleic acid and polypeptide selection
WO2003044194A1 (en) * 2001-11-16 2003-05-30 Proteonova, Inc. Selection and evolution of nucleic acids and polypeptides
SE0003002D0 (sv) * 2000-08-22 2000-08-22 Primert Ab New sequences
FR2822164B1 (fr) 2001-03-19 2004-06-18 Centre Nat Rech Scient Polypeptides derives des arn polymerases, et leurs utilisations
US20030171253A1 (en) * 2001-04-19 2003-09-11 Averil Ma Methods and compositions relating to modulation of A20
US20050137155A1 (en) 2001-05-18 2005-06-23 Sirna Therapeutics, Inc. RNA interference mediated treatment of Parkinson disease using short interfering nucleic acid (siNA)
EP1903054A3 (de) 2001-06-05 2008-07-23 CureVac GmbH Stabilisierte mRNA mit erhöhtem G/C-Gehalt und optimierter Codon Usage für die Gentherapie
DE10162480A1 (de) 2001-12-19 2003-08-07 Ingmar Hoerr Die Applikation von mRNA für den Einsatz als Therapeutikum gegen Tumorerkrankungen
DE10229872A1 (de) 2002-07-03 2004-01-29 Curevac Gmbh Immunstimulation durch chemisch modifizierte RNA
US9567591B2 (en) 2003-05-15 2017-02-14 Mello Biotechnology, Inc. Generation of human embryonic stem-like cells using intronic RNA
GB0316089D0 (en) 2003-07-09 2003-08-13 Xo Bioscience Ltd Differentiation method
DE10335833A1 (de) 2003-08-05 2005-03-03 Curevac Gmbh Transfektion von Blutzellen mit mRNA zur Immunstimulation und Gentherapie
ATE536418T1 (de) 2004-06-07 2011-12-15 Protiva Biotherapeutics Inc Lipidverkapselte interferenz-rna
EP1773857A4 (en) 2004-07-02 2009-05-13 Protiva Biotherapeutics Inc THE IMMUNE SYSTEM STIMULATING SIRNA MOLECULES AND APPLICATIONS THEREOF
DE102005023170A1 (de) 2005-05-19 2006-11-23 Curevac Gmbh Optimierte Formulierung für mRNA
US9012219B2 (en) 2005-08-23 2015-04-21 The Trustees Of The University Of Pennsylvania RNA preparations comprising purified modified RNA for reprogramming cells
HUE043492T2 (hu) 2005-08-23 2019-08-28 Univ Pennsylvania Módosított nukleozidokat tartalmazó RNS és eljárások az alkalmazására
US20070087437A1 (en) 2005-10-14 2007-04-19 Jifan Hu Methods for rejuvenating cells in vitro and in vivo
DE102006007433A1 (de) 2006-02-17 2007-08-23 Curevac Gmbh Adjuvanz in Form einer Lipid-modifizierten Nukleinsäure
WO2007120863A2 (en) 2006-04-14 2007-10-25 Epicentre Technologies Kits and methods for generating 5' capped rna
DE102006051516A1 (de) 2006-10-31 2008-05-08 Curevac Gmbh (Basen-)modifizierte RNA zur Expressionssteigerung eines Proteins
US20100184051A1 (en) 2007-05-30 2010-07-22 The General Hospital Corporation Methods of generating pluripotent cells from somatic cells
EP2173872B1 (en) 2007-06-29 2014-04-02 CellScript, Inc. Copy dna and sense rna
EP2072618A1 (en) 2007-12-14 2009-06-24 Johannes Gutenberg-Universität Mainz Use of RNA for reprogramming somatic cells
GB0801215D0 (en) 2008-01-23 2008-02-27 Univ Sheffield Cell re-programming
EP2250252A2 (en) 2008-02-11 2010-11-17 Cambridge Enterprise Limited Improved reprogramming of mammalian cells, and the cells obtained
NZ588583A (en) 2008-04-15 2012-08-31 Protiva Biotherapeutics Inc Novel lipid formulations for nucleic acid delivery
WO2009127230A1 (en) 2008-04-16 2009-10-22 Curevac Gmbh MODIFIED (m)RNA FOR SUPPRESSING OR AVOIDING AN IMMUNOSTIMULATORY RESPONSE AND IMMUNOSUPPRESSIVE COMPOSITION
WO2010008486A2 (en) 2008-06-24 2010-01-21 Parkinsons Institute Pluripotent cell lines and methods of use thereof
GB0905507D0 (en) 2009-03-31 2009-05-13 Dow Corning Organopol Ysiloxane Compositions Containing An Active Material
WO2010123501A1 (en) 2009-04-22 2010-10-28 Massachusetts Institute Of Technology Innate immune suppression enables repeated delivery of long rna molecules
EP3165234B1 (de) 2009-07-31 2019-04-03 ethris GmbH Rna mit einer kombination aus unmodifizierten und modifizierten nucleotiden zur proteinexpression
US20130189741A1 (en) 2009-12-07 2013-07-25 Cellscript, Inc. Compositions and methods for reprogramming mammalian cells
KR101878502B1 (ko) 2009-12-07 2018-07-13 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 세포 리프로그래밍을 위한 정제된 변형 ｒｎａ를 포함하는 ｒｎａ 제제
EP3072961A1 (en) 2010-04-16 2016-09-28 Children's Medical Center Corporation Sustained polypeptide expression from synthetic, modified rnas and uses thereof
CA2807552A1 (en) 2010-08-06 2012-02-09 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
US8765414B2 (en) 2011-03-15 2014-07-01 The Board Of Trustees Of The Leland Stanford Junior University GPCR fusion protein containing an N-terminal autonomously folding stable domain, and crystals of the same
JP2014511687A (ja) 2011-03-31 2014-05-19 モデルナ セラピューティクス インコーポレイテッド 工学操作された核酸の送達および製剤
US9862926B2 (en) 2011-06-27 2018-01-09 Cellscript, Llc. Inhibition of innate immune response
EP4721752A2 (en) 2011-12-30 2026-04-08 Cellscript, Llc Herstellung und verwendung von in vitro-synthetisierter ssrna zur einführung in säugetierzellen zur induktion einer biologischen oder biochemischen wirkung

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