DK2850189T3 - Sammensætninger og fremgangsmåder til modulering af genekspression - Google Patents

Sammensætninger og fremgangsmåder til modulering af genekspression Download PDF

Info

Publication number
DK2850189T3
DK2850189T3 DK13791343.0T DK13791343T DK2850189T3 DK 2850189 T3 DK2850189 T3 DK 2850189T3 DK 13791343 T DK13791343 T DK 13791343T DK 2850189 T3 DK2850189 T3 DK 2850189T3
Authority
DK
Denmark
Prior art keywords
homo sapiens
utrn
sapiens
sequence
nucleotides
Prior art date
Application number
DK13791343.0T
Other languages
English (en)
Inventor
Arthur M Krieg
Romesh Subramanian
James Mcswiggen
Jeannie T Lee
Original Assignee
Translate Bio Ma Inc
Massachusetts Gen Hospital
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=49584310&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DK2850189(T3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Translate Bio Ma Inc, Massachusetts Gen Hospital filed Critical Translate Bio Ma Inc
Application granted granted Critical
Publication of DK2850189T3 publication Critical patent/DK2850189T3/da

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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
    • C12N2310/11—Antisense
    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • 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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • 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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
    • 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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
    • 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
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
    • 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
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3517—Marker; Tag
    • 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
    • C12N2310/35—Nature of the modification
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3521—Methyl
    • 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
    • C12N2310/35—Nature of the modification
    • C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
    • C12N2310/3533—Halogen

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)

Claims (19)

1. Fremgangsmåde til at vælge et kandidat-oligonukleotid til at aktivere ekspression af et målgen, hvilken fremgangsmåde omfatter: at vælge en PRC2-associeret region i en første nukleotidsekvens, hvor den første nukleotidsekvens er placeret i en position i et første kromosom mellem 50 kilobaser opstrøms af en 5'-ende af målgenet og 50 kilobaser nedstrøms af en 3'-ende af målgenet, hvor den PRC2-associerede region er en region af et RNA, der er beskyttet mod en nuklease i et RNA-immunopræcipitationsassay, der anvender et antistof som er målrettet en komponent af PRC2; at bestemme en anden nukleotidsekvens der er komplementær til mindst 8 på hinanden følgende nukleotider af den PRC2-associerede region; og at vælge som kandidat-oligonukleotidet, et enkeltstrenget oligonukleotid omfattende den anden nukleotidsekvens, hvor oligonukleotidet har mindst ét af følgende kendetegn: a) en sekvens: 5'-X-Y-Z, hvor X er et hvilket som helst nukleotid, Y er en nukleotidsekvens på 6 nukleotider i længde, der ikke er en seed-sekvens af et humant microRNA, og Z er en nukleotidsekvens på 1 til 23 nukleotider i længde, hvor X er forankret ved den 5'-ende af oligonukleotidet; b) en sekvens, der ikke omfatter tre eller flere på hinanden følgende guanosinnukleotider; c) en sekvens, der er komplementær til en PRC2-associeret region, som koder for et RNA, der danner en sekundær struktur omfattende mindst to enkeltstrengede sløjfer; eller d) en sekvens, der har større end 60 % G-C-indhold; hvor det enkeltstrengede oligonukleotid er 8 til 30 nukleotider i længde.
2. Fremgangsmåden ifølge krav 1, hvor oligonukleotidet har mindst to af kendetegnene a), b), c) og d).
3. Fremgangsmåden ifølge krav 1, hvor oligonukleotidet har mindst tre kendetegn af a), b), c) og d).
4. Fremgangsmåde til at vælge et sæt af oligonukleotider, der er beriget i oligonukleotider som aktiverer ekspression af et målgen, hvilken fremgangsmåde omfatter: at vælge en PRC2-associeret region i en første nukleotidsekvens der er placeret i en position i et første kromosom mellem 50 kilobaser opstrøms af en 5'-ende af målgenet og 50 kilobaser nedstrøms af en 3'-ende af målgenet, hvor den PRC2-associerede region er en region af et RNA, der er beskyttet mod en nuklease i et RNA-immunopræcipitationsassay, der anvender et antistof som er målrettet en komponent af PRC2; at vælge et sæt af oligonukleotider, hvor hvert oligonukleotid i sættet omfatter en anden nukleotidsekvens der er komplementær til mindst 8 på hinanden følgende nukleotider af den PRC2-associerede region, og har mindst ét af de følgende kendetegn: a) en sekvens: 5'-X-Y-Z, hvor X er et hvilket som helst nukleotid, Y er en nukleotidsekvens på 6 nukleotider i længde, der ikke er en human seed-sekvens af et microRNA, og Z er en nukleotidsekvens på 1 til 23 nukleotider i længde, hvor X er forankret ved den 5'-ende af oligonukleotidet; b) en sekvens, der ikke omfatter tre eller flere på hinanden følgende guanosinnukleotider; c) en sekvens, der er komplementær til en PRC2-associeret region, som koder for et RNA, der danner en sekundær struktur omfattende mindst to enkeltstrengede sløjfer; og/eller d) en sekvens, der har større end 60 % G-C-indhold; og hvor sættet af oligonukleotider er beriget i oligonukleotider der aktiverer ekspression af et målgen; hvor hver af oligonukleotiderne er 8 til 30 nukleotider i længde.
5. Fremgangsmåden ifølge krav 4, hvor hver af oligonukleotiderne i sættet deler mindst to af kendetegnene a), b), c) og d).
6. Fremgangsmåden ifølge krav 4, hvor hver af oligonukleotiderne i sættet deler mindst tre af kendetegnene a), b), c) og d).
7. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 6, hvor det første kromosom er et kromosom af en første art, og hvor fremgangsmåden yderligere omfatter at bestemme at den anden nukleotidsekvens er komplementær til en anden region af et andet kromosom af en anden art, hvor den anden region er placeret mellem 50 kilobaser opstrøms af en 5'-ende af en homolog af målgenet og 50 kilobaser nedstrøms af en 3'-ende af homologen af målgenet.
8. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 7, hvor den første nukleotidsekvens er placeret på strengen af det første kromosom omfattende sense-strengen af målgenet eller den første nukleotidsekvens er placeret på strengen af det første kromosom omfattende antisense-strengen af målgenet.
9. Enkeltstreng et oligonukleotid til anvendelse i behandlingen afen sygdom, hvor behandlingen involverer at opregulere ekspression af et gen målrettet af det PRC2-bindende RNA og hvor det enkeltstrengede oligonukleotid omfatter en region af komplementaritet der er komplementær med mindst 8 på hinanden følgende nukleotider afen PRC2-associeret region placeret i et første kromosom mellem 50 kilobaser opstrøms afen 5'-ende af et målgen og 50 kilobaser nedstrøms af en 3'-ende af målgenet, hvor den PRC2-associerede region er en region af et RNA, der er beskyttet mod en nuklease i et RNA- immunopræcipitationsassay, der anvender et antistof som er målrettet en komponent af PRC2, og hvor oligonukleotidet har mindst én af: a) en sekvens omfattende 5'-X-Y-Z, hvor X er et hvilket som helst nukleotid, Y er en nukleotidsekvens på 6 nukleotider i længde, der ikke er en human seed-sekvens af et microRNA, og Z er en nukleotidsekvens på 1 til 23 nukleotider i længde; b) en sekvens, der ikke omfatter tre eller flere på hinanden følgende guanosinnukleotider; c) en sekvens, der er komplementærtil en PRC2-associeret region, som koder for et RNA, der danner en sekundær struktur omfattende mindst to enkeltstrengede sløjfer; og/eller d) en sekvens, der har større end 60 % G-C-indhold; hvor oligonukleotidet er 8 til 30 nukleotider i længde.
10. Enkeltstrenget oligonukleotid til anvendelse ifølge krav 9 hvor (a) sygdommen er kræft eller en stofskifte- eller luftvejssygdom eller (b) anvendelsen omfatter pulmonær levering og, eventuelt, sygdommen er en sygdom i lungerne.
11. Det enkeltstrengede oligonukleotid til anvendelse ifølge krav 9 eller 10, hvor oligonukleotidet har mindst to af kendetegnene a), b), c) og d).
12. Det enkeltstrengede oligonukleotid til anvendelse ifølge krav 9 eller 10, hvor oligonukleotidet har mindst tre af kendetegnene a), b), c) og d).
13. Det enkeltstrengede oligonukleotid til anvendelse ifølge et hvilket som helst af kravene 9 til 12, hvor de mindst 8 på hinanden følgende nukleotider af den PRC2-associerede region i strengen af kromosomet omfattende sense-strengen af målgenet, eller hvor de mindst 8 på hinanden følgende nukleotider af den PRC2-associerede region i strengen af kromosomet omfattende antisense-strengen af målgenet.
14. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 8 eller det enkeltstrengede oligonukleotid til anvendelse ifølge et hvilket som helst af kravene 9 til 13, hvor den PRC2-associerede region (a) er opstrøms af den 5'-ende af målgenet; (b) er nedstrøms af den 3'-ende af målgenet; (c) er i et intron af målgenet; (d) er i et exon af målgenet; eller (e) spænder over en intron-exon-forbindelse, en 5'-UTR-exon-forbindelse eller en 3'-UTR-exon-forbindelse af målgenet.
15. Det enkeltstrengede oligonukleotid til anvendelse ifølge et hvilket som helst af kravene 9 til 14, hvor mindst ét nukleotid af oligonukleotidet er en nukleotid-analog.
16. Det enkeltstrengede oligonukleotid til anvendelse ifølge et hvilket som helst af kravene 9 til 15, hvor mindst ét nukleotid af oligonukleotidet omfatter en 2' O-methyl; eller hvor oligonukleotidet omfatter mindst ét ribonukleotid, mindst ét deoxyribonukleotid, eller mindst ét broforbundet nukleotid, eventuelt hvor det broforbundne nukleotid er et LNA-nukleotid, et cEt-nukleotid eller en ENA-nukleotid-analog.
17. Det enkeltstrengede oligonukleotid til anvendelse ifølge krav 15, hvor nukleotiderne af oligonukleotidet omfatter: a) alternerende deoxyribonukleotider og 2'-fluor-deoxyribonukleotider; b) alternerende deoxyribonukleotider og 2'-O-methyl-nukleotider; c) alternerende deoxyribonukleotider og ENA-nukleotid-analoger; d) alternerende deoxyribonukleotider og LNA-nukleotider; eller e) alternerende LNA-nukleotider og 2'-O-methyl-nukleotider.
18. Det enkeltstrengede oligonukleotid til anvendelse ifølge et hvilket som helst af kravene 9 til 17, yderligere omfattende phosphorthioat-internukleotidkoblingermellem mindst to nukleotider, eventuelt omfattende phosphorthioat-internukleotidkoblinger mellem alle nukleotider.
19. Det enkeltstrengede oligonukleotid til anvendelse ifølge et hvilket som helst af kravene 9-18, hvor behandlingen af en sygdom er til behandling af en lidelse associeret med mindskede niveauer af et målgen hos et individ.
DK13791343.0T 2012-05-16 2013-05-16 Sammensætninger og fremgangsmåder til modulering af genekspression DK2850189T3 (da)

Applications Claiming Priority (18)

Application Number Priority Date Filing Date Title
US201261647925P 2012-05-16 2012-05-16
US201261647886P 2012-05-16 2012-05-16
US201261648016P 2012-05-16 2012-05-16
US201261647949P 2012-05-16 2012-05-16
US201261647901P 2012-05-16 2012-05-16
US201261648041P 2012-05-16 2012-05-16
US201261647858P 2012-05-16 2012-05-16
US201261648021P 2012-05-16 2012-05-16
US201261648051P 2012-05-16 2012-05-16
US201261648058P 2012-05-16 2012-05-16
US201261719394P 2012-10-27 2012-10-27
US201361786232P 2013-03-14 2013-03-14
US201361785778P 2013-03-14 2013-03-14
US201361785885P 2013-03-14 2013-03-14
US201361785956P 2013-03-14 2013-03-14
US201361785832P 2013-03-14 2013-03-14
US201361785529P 2013-03-14 2013-03-14
PCT/US2013/041461 WO2013173652A1 (en) 2012-05-16 2013-05-16 Compositions and methods for modulating gene expression

Publications (1)

Publication Number Publication Date
DK2850189T3 true DK2850189T3 (da) 2019-02-25

Family

ID=49584310

Family Applications (1)

Application Number Title Priority Date Filing Date
DK13791343.0T DK2850189T3 (da) 2012-05-16 2013-05-16 Sammensætninger og fremgangsmåder til modulering af genekspression

Country Status (10)

Country Link
US (2) US20150133362A1 (da)
EP (2) EP3511416A1 (da)
JP (1) JP2015518714A (da)
KR (1) KR102028784B1 (da)
CN (1) CN104583398A (da)
AU (1) AU2013262663A1 (da)
CA (1) CA2873809A1 (da)
DK (1) DK2850189T3 (da)
EA (1) EA201492114A1 (da)
WO (1) WO2013173652A1 (da)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9920317B2 (en) 2010-11-12 2018-03-20 The General Hospital Corporation Polycomb-associated non-coding RNAs
WO2012065143A1 (en) 2010-11-12 2012-05-18 The General Hospital Corporation Polycomb-associated non-coding rnas
US9580708B2 (en) 2011-09-14 2017-02-28 Rana Therapeutics, Inc. Multimeric oligonucleotides compounds
EA201492116A1 (ru) 2012-05-16 2015-05-29 Рана Терапьютикс, Инк. Композиции и способы для модулирования экспрессии mecp2
AP2014008100A0 (en) 2012-05-16 2014-12-31 Gen Hospital Corp Compositions and methods for modulating hemoglobingene family expression
US10837014B2 (en) 2012-05-16 2020-11-17 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
EP2849801A4 (en) * 2012-05-16 2016-05-25 Rana Therapeutics Inc COMPOSITIONS AND METHODS FOR MODULATING THE EXPRESSION OF APOA1 AND ABCA1
AU2013262699A1 (en) * 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating ATP2A2 expression
SG11201407486PA (en) 2012-05-16 2014-12-30 Rana Therapeutics Inc Compositions and methods for modulating utrn expression
AU2013262649A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating smn gene family expression
WO2014043544A1 (en) 2012-09-14 2014-03-20 Rana Therapeutics, Inc. Multimeric oligonucleotide compounds
AU2014274730A1 (en) * 2013-06-07 2016-01-21 Rana Therapeutics, Inc. Compositions and methods for modulating FOXP3 expression
WO2015023941A1 (en) 2013-08-16 2015-02-19 Rana Therapeutics, Inc. Oligonucleotides targeting euchromatin regions of genes
WO2015051283A1 (en) 2013-10-04 2015-04-09 Rana Therapeutics, Inc. Compositions and methods for treating amyotrophic lateral sclerosis
WO2016070060A1 (en) 2014-10-30 2016-05-06 The General Hospital Corporation Methods for modulating atrx-dependent gene repression
WO2016130943A1 (en) 2015-02-13 2016-08-18 Rana Therapeutics, Inc. Hybrid oligonucleotides and uses thereof
US20180030452A1 (en) * 2015-02-13 2018-02-01 Translate Bio Ma, Inc. Targeting oligonucleotides and uses thereof to modulate gene expression
EP3271460A4 (en) 2015-03-17 2019-03-13 The General Hospital Corporation INTERACTOME RNA OF COMPLEX REPRESSIVE POLYCOMB 1 (PRC1)
AU2017353907B2 (en) 2016-11-01 2023-11-30 The Research Foundation For The State University Of New York 5-halouracil-modified microRNAs and their use in the treatment of cancer
JP2019535839A (ja) 2016-11-29 2019-12-12 ピュアテック ヘルス エルエルシー 治療剤の送達のためのエクソソーム
CN106636120B (zh) * 2017-02-17 2019-08-30 中国人民解放军第三军医大学第三附属医院 可编码ArtRD蛋白基因及其蛋白和应用
AU2018330495A1 (en) 2017-09-08 2020-03-26 Mina Therapeutics Limited Stabilized hnf4a sarna compositions and methods of use
EP3679140B1 (en) 2017-09-08 2022-11-16 MiNA Therapeutics Limited Stabilized cebpa sarna compositions and methods of use
US20220340898A1 (en) * 2018-08-01 2022-10-27 Yale University Compositions and Methods for Identification of Membrane Targets for Enhancement of T cell Activity Against Cancer
EP3850083A4 (en) * 2018-09-14 2022-06-29 Shinozaki, Gen Systems and methods for detection of delirium risk using epigenetic markers
CA3120534A1 (en) * 2018-12-29 2020-07-02 Ractigen Therapeutics Oligomeric nucleic acid molecule and use thereof
CA3151996A1 (en) 2019-08-19 2021-02-25 Mina Therapeutics Limited Oligonucleotide conjugate compositions and methods of use
US20240102023A1 (en) * 2019-10-14 2024-03-28 University Of Cincinnati Novel rna aptamer intervenes estrogen receptor interaction with coactivator med1 to overcome breast cancer metastasis
CN113444726B (zh) * 2021-06-28 2022-07-29 甘肃农业大学 一种与仔猪细菌性腹泻相关的lncRNA ALDB-898及其应用
CN114540498A (zh) * 2022-03-09 2022-05-27 厦门飞朔生物技术有限公司 一种基于dna甲基化的浸润性神经胶质瘤的分类装置

Family Cites Families (208)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US538A (en) 1837-12-26 Self-separating link for connecting railroad-cars and locomotives
US5552A (en) 1848-05-09 Paul stillman
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
US4671638A (en) 1985-10-11 1987-06-09 Eastman Kodak Company Moving coil electromagnetic actuator and shutter employing same
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
DE3788914T2 (de) 1986-09-08 1994-08-25 Ajinomoto Kk Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere.
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
CA1340032C (en) 1987-06-24 1998-09-08 Jim Haralambidis Lucleoside derivatives
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
ATE151467T1 (de) 1987-11-30 1997-04-15 Univ Iowa Res Found Durch modifikationen an der 3'-terminalen phosphodiesterbindung stabilisierte dna moleküle, ihre verwendung als nukleinsäuresonden sowie als therapeutische mittel zur hemmung der expression spezifischer zielgene
US5403711A (en) 1987-11-30 1995-04-04 University Of Iowa Research Foundation Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
JPH03503894A (ja) 1988-03-25 1991-08-29 ユニバーシィティ　オブ　バージニア　アランミ　パテンツ　ファウンデイション オリゴヌクレオチド　ｎ‐アルキルホスホラミデート
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5220007A (en) 1990-02-15 1993-06-15 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
WO1991013080A1 (en) 1990-02-20 1991-09-05 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
EP0745689A3 (en) 1990-05-11 1996-12-11 Microprobe Corporation A dipstick for a nucleic acid hybridization assay
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
EP0544824B1 (en) 1990-07-27 1997-06-11 Isis Pharmaceuticals, Inc. Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
CA2088673A1 (en) 1990-08-03 1992-02-04 Alexander L. Weis Compounds and methods for inhibiting gene expression
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
AU662298B2 (en) 1990-09-20 1995-08-31 Gilead Sciences, Inc. Modified internucleoside linkages
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
EP0556301B1 (en) 1990-11-08 2001-01-10 Hybridon, Inc. Incorporation of multiple reporter groups on synthetic oligonucleotides
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
AU6412794A (en) 1993-03-31 1994-10-24 Sterling Winthrop Inc. Oligonucleotides with amide linkages replacing phosphodiester linkages
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
ATE196311T1 (de) 1993-12-09 2000-09-15 Univ Jefferson Verbindungen und verfahren zur ortsspezifischen mutation in eukaryotischen zellen
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
WO1999067378A1 (en) 1998-06-19 1999-12-29 Mcgill University ANTISENSE OLIGONUCLEOTIDE CONSTRUCTS BASED ON β-ARABINOFURANOSE AND ITS ANALOGUES
EP1152009B2 (en) 1999-02-12 2017-09-06 Daiichi Sankyo Company, Limited Novel nucleosides and oligonucleotide analogues
US6287860B1 (en) 2000-01-20 2001-09-11 Isis Pharmaceuticals, Inc. Antisense inhibition of MEKK2 expression
US20050003369A1 (en) 2002-10-10 2005-01-06 Affymetrix, Inc. Method for depleting specific nucleic acids from a mixture
FR2853663B1 (fr) * 2003-04-14 2007-08-31 Aventis Pharma Sa Procede d'obtention de lignees de mastocytes a partir de tissus de porcs et procede de production de molecules de type heparine
WO2005001110A2 (en) 2003-05-29 2005-01-06 The Salk Institute For Biological Studies Transcriptional regulation of gene expression by small double-stranded modulatory rna
WO2005013901A2 (en) 2003-07-31 2005-02-17 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for use in modulation of small non-coding rnas
GB0324854D0 (en) 2003-10-24 2003-11-26 Expresson Biosystems Ltd App/ena antisense
EP1959012A3 (en) 2004-12-29 2009-12-30 Exiqon A/S Novel oligonucleotide compositions and probe sequences useful for detection and analysis of microRNAs and their target mRNAs
CA2604532C (en) 2005-04-15 2017-03-07 The Regents Of The University Of California Small activating rna molecules and methods of use
ES2450593T3 (es) 2005-07-01 2014-03-25 Index Pharmaceuticals Ab Método inmunoestimulante
EP2431467A3 (en) 2005-11-17 2012-05-02 Board Of Regents, The University Of Texas Modulation of gene expression by oligomers targeted to chromosomal DNA
CN103301475B (zh) 2005-12-28 2016-08-03 斯克里普斯研究所 药物组合物和表达载体以及调节基因表达的方法和核酸分子的应用
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
KR20130042043A (ko) 2006-01-27 2013-04-25 아이시스 파마수티컬즈 인코포레이티드 6-변형된 바이시클릭 핵산 유사체
CA3042781C (en) 2006-04-03 2021-10-19 Roche Innovation Center Copenhagen A/S Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
JP5731115B2 (ja) * 2006-05-05 2015-06-10 アイシス ファーマシューティカルズ， インコーポレーテッド 遺伝子発現を調節するための化合物および方法
US20100216864A1 (en) 2006-10-09 2010-08-26 Ellen Marie Straarup RNA Antagonist Compounds for the Modulation of PCSK9
EP1942192A1 (en) 2007-01-08 2008-07-09 Heinrich-Pette-Institut für experimentelle Virologie und Immunologie Use of a tailored recombinase for the treatment of retroviral infections
WO2008103761A2 (en) * 2007-02-20 2008-08-28 Sequenom, Inc. Methods and compositions for cancer diagnosis and treatment based on nucleic acid methylation
AU2008244211B2 (en) 2007-05-01 2014-08-21 Santaris Pharma A/S RNA antagonist compounds for the modulation of beta-catenin
EP2155877A2 (en) 2007-05-11 2010-02-24 Santaris Pharma A/S Rna antagonist compounds for the modulation of her3
TR201000668T1 (tr) 2007-07-31 2010-06-21 The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Neoplasti̇k veya enfeksi̇yoz bozukluklara yöneli̇k i̇mmunoprofi̇laksi̇ veya i̇mmünoterapi̇ i̇çi̇n poli̇pepti̇d-nüklei̇k asi̇t konjugati
ES2463665T3 (es) 2007-10-04 2014-05-28 Stella Aps Tratamiento de combinación para el tratamiento de infección por virus de la hepatitis C
AU2009235941A1 (en) 2008-04-07 2009-10-15 Riken RNA molecules and uses thereof
US20110224280A1 (en) 2008-04-16 2011-09-15 Niels Fisker Nielsen Pharmaceutical Composition Comprising Anti PCSK9 Oligomers
CA2729897A1 (en) 2008-07-03 2010-01-07 Santaris Pharma A/S Rna antagonist compounds for the inhibition of expression of mitochondrial glycerol-3-phosphate acyltransferase 1 (mtgpat1)
CA2730641A1 (en) 2008-07-15 2010-01-21 Santaris Pharma A/S Rna antagonists targeting gli2
CN102239260B (zh) 2008-10-03 2017-04-12 库尔纳公司 通过抑制针对载脂蛋白‑a1的天然反义转录物治疗载脂蛋白‑a1相关疾病
US8927511B2 (en) 2008-12-04 2015-01-06 Curna, Inc. Treatment of vascular endothelial growth factor (VEGF) related diseases by inhibition of natural antisense transcript to VEGF
CA2745811C (en) 2008-12-04 2021-07-13 Joseph Collard Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene
JP6091752B2 (ja) 2008-12-04 2017-03-08 クルナ・インコーポレーテッド Ｅｐｏに対する天然アンチセンス転写物の抑制によるエリスロポエチン（ｅｐｏ）関連疾患の治療
MX366774B (es) 2008-12-04 2019-07-24 Curna Inc Uso de oligonucleótidos antisentido en la inhibición de transcrito antisentido natural para sirtuina 1.
JP5793423B2 (ja) 2008-12-31 2015-10-14 ロシュ・イノベーション・センター・コペンハーゲン・アクティーゼルスカブＲｏｃｈｅ Ｉｎｎｏｖａｔｉｏｎ Ｃｅｎｔｅｒ Ｃｏｐｅｎｈａｇｅｎ Ａ／Ｓ 急性冠症候群の治療のためのＬＮＡＡｐｏＢアンチセンスオリゴマーの使用
JP6066035B2 (ja) 2009-02-12 2017-01-25 クルナ・インコーポレーテッド グリア細胞由来神経栄養因子（ｇｄｎｆ）関連疾病の、ｇｄｎｆに対する天然アンチセンス転写物の抑制による治療
US9074210B2 (en) 2009-02-12 2015-07-07 Curna, Inc. Treatment of brain derived neurotrophic factor (BDNF) related diseases by inhibition of natural antisense transcript to BDNF
US9464287B2 (en) 2009-03-16 2016-10-11 Curna, Inc. Treatment of nuclear factor (erythroid-derived 2)-like 2 (NRF2) related diseases by inhibition of natural antisense transcript to NRF2
MX2011009752A (es) 2009-03-17 2011-09-29 Opko Curna Llc Tratamiento de enfermedades relacionadas a homologo tipo delta 1(dlk1) por inhibicion de transcrito antisentido natural a homologo tipo delta (dlk1).
EP2421972A2 (en) 2009-04-24 2012-02-29 The Board of Regents of The University of Texas System Modulation of gene expression using oligomers that target gene regions downstream of 3' untranslated regions
EP2421970B1 (en) 2009-04-24 2016-09-07 Roche Innovation Center Copenhagen A/S Pharmaceutical compositions for treatment of hcv patients that are non-responders to interferon
CN102639151B (zh) 2009-05-01 2017-03-22 库尔纳公司 通过针对hbf/hbg的天然反义转录物的抑制治疗血红蛋白（hbf/hbg）相关疾病
WO2010129746A2 (en) 2009-05-06 2010-11-11 Curna, Inc. Treatment of tristetraproline (ttp) related diseases by inhibition of natural antisense transcript to ttp
JP5883782B2 (ja) 2009-05-06 2016-03-15 クルナ・インコーポレーテッド 脂質輸送代謝遺伝子に対する天然アンチセンス転写物の抑制による脂質輸送代謝遺伝子関連疾患の治療
CN102459597B (zh) 2009-05-08 2020-06-30 库尔纳公司 通过针对dmd家族的天然反义转录物的抑制治疗肌营养蛋白家族相关疾病
CA2762369C (en) 2009-05-18 2021-12-28 Joseph Collard Treatment of reprogramming factor related diseases by inhibition of natural antisense transcript to a reprogramming factor
EP2432882B1 (en) 2009-05-22 2019-12-25 CuRNA, Inc. TREATMENT OF TRANSCRIPTION FACTOR E3 (TFE3) and INSULIN RECEPTOR SUBSTRATE 2 (IRS2) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPT TO TFE3
CN103221541B (zh) 2009-05-28 2017-03-01 库尔纳公司 通过抑制抗病毒基因的天然反义转录物来治疗抗病毒基因相关疾病
CA2765700C (en) 2009-06-16 2021-01-05 Opko Curna, Llc Treatment of collagen gene related diseases by inhibition of natural antisense transcript to a collagen gene
ES2629339T3 (es) 2009-06-16 2017-08-08 Curna, Inc. Tratamiento de enfermedades relacionadas con la paraoxonasa 1 (pon1) por inhibición de transcrito antisentido natural a pon1
US8859515B2 (en) 2009-06-24 2014-10-14 Curna, Inc. Treatment of tumor necrosis factor receptor 2 (TNFR2) related diseases by inhibition of natural antisense transcript to TNFR2
CN102482672B (zh) 2009-06-26 2016-11-09 库尔纳公司 通过抑制唐氏综合征基因的天然反义转录物治疗唐氏综合征基因相关疾病
CN101619312B (zh) 2009-07-10 2011-04-20 四川大学 人黑色素瘤细胞特异表达的长非编码rna序列及其用途
US9234199B2 (en) 2009-08-05 2016-01-12 Curna, Inc. Treatment of insulin gene (INS) related diseases by inhibition of natural antisense transcript to an insulin gene (INS)
EP2464731B1 (en) 2009-08-11 2016-10-05 CuRNA, Inc. Treatment of adiponectin (adipoq) related diseases by inhibition of natural antisense transcript to an adiponectin (adipoq)
EP2467482A4 (en) 2009-08-21 2013-12-11 Curna Inc TREATMENT OF DISEASES RELATED TO "CIP PROTEIN CHIP EXTREME (PROTEIN INTERACTING WITH HSP70)" BY INHIBITION OF CHIP NATURAL ANTISENSE TRANSCRIPT
CA2771172C (en) 2009-08-25 2021-11-30 Opko Curna, Llc Treatment of 'iq motif containing gtpase activating protein' (iqgap) related diseases by inhibition of natural antisense transcript to iqgap
WO2011025862A2 (en) 2009-08-28 2011-03-03 Curna, Inc. Treatment of atp-binding cassette sub-family b member 1 (abcb1) related diseases by inhibition of natural antisense transcript to abcb1
WO2011038205A2 (en) 2009-09-25 2011-03-31 Curna, Inc. Treatment of growth hormone (gh) related diseases by inhibition of natural antisense transcript to gh
JP6025567B2 (ja) 2009-12-16 2016-11-16 カッパーアールエヌエー，インコーポレイテッド 膜結合転写因子ペプチダーゼ、部位１（ｍｂｔｐｓ１）に対する天然アンチセンス転写物の阻害によるｍｂｔｐｓ１関連性疾患の治療
WO2011079263A2 (en) 2009-12-23 2011-06-30 Curna, Inc. Treatment of uncoupling protein 2 (ucp2) related diseases by inhibition of natural antisense transcript to ucp2
US8940708B2 (en) 2009-12-23 2015-01-27 Curna, Inc. Treatment of hepatocyte growth factor (HGF) related diseases by inhibition of natural antisense transcript to HGF
RU2615450C2 (ru) 2009-12-29 2017-04-04 Курна, Инк. Лечение заболеваний, связанных с ядерным респираторным фактором 1(nrf1), путем ингибирования природного антисмыслового транскрипта к nrf1
RU2611186C2 (ru) 2009-12-29 2017-02-21 Курна, Инк. ЛЕЧЕНИЕ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С ОПУХОЛЕВЫМ БЕЛКОМ 63 (р63), ПУТЕМ ИНГИБИРОВАНИЯ ПРИРОДНОГО АНТИСМЫСЛОВОГО ТРАНСКРИПТА К р63
US8946181B2 (en) 2010-01-04 2015-02-03 Curna, Inc. Treatment of interferon regulatory factor 8 (IRF8) related diseases by inhibition of natural antisense transcript to IRF8
WO2011085066A2 (en) 2010-01-06 2011-07-14 Curna, Inc. Treatment of pancreatic developmental gene related diseases by inhibition of natural antisense transcript to a pancreatic developmental gene
CA2786535C (en) 2010-01-11 2019-03-26 Curna, Inc. Treatment of sex hormone binding globulin (shbg) related diseases by inhibition of natural antisense transcript to shbg
RU2611192C2 (ru) 2010-01-25 2017-02-21 Курна, Инк. ЛЕЧЕНИЕ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С РНКазой Н1, ПУТЕМ ИНГИБИРОВАНИЯ ПРИРОДНОГО АНТИСМЫСЛОВОГО ТРАНСКРИПТА К РНКазе Н1
WO2011097582A2 (en) 2010-02-08 2011-08-11 Opko Curna Llc Treatment of arachidonate 12-lipoxygenase, 12r type (alox12b) related diseases by inhibition of natural antisense transcript to alox12b
EP2539452B1 (en) 2010-02-22 2016-07-27 CuRNA, Inc. Treatment of pyrroline-5-carboxylate reductase 1 (pycr1) related diseases by inhibition of natural antisense transcript to pycr1
ES2657969T3 (es) 2010-04-02 2018-03-07 Curna, Inc. Tratamiento de enfermedades relacionadas con el Factor 3 estimulante de colonias (CSF3) por inhibición del transcrito antisentido natural a CSF3
EP2556160A4 (en) 2010-04-09 2013-08-21 Curna Inc TREATMENT OF ILLNESSES ASSOCIATED WITH FIBROBLASTIC GROWTH FACTOR 21 (FGF21) BY INHIBITION OF THE NATURAL ANTISENSE TRANSCRIPT AGAINST FGF21
EP2558578B1 (en) * 2010-04-13 2015-10-28 Life Technologies Corporation Compositions and methods for inhibition of nucleic acids function
RU2018110642A (ru) 2010-05-03 2019-02-27 Курна, Инк. Лечение заболеваний, связанных с сиртуином (sirt), путем ингибирования природного антисмыслового транскрипта к сиртуину (sirt)
TWI531370B (zh) 2010-05-14 2016-05-01 可娜公司 藉由抑制ｐａｒ４天然反股轉錄本治療ｐａｒ４相關疾病
AR081295A1 (es) 2010-05-19 2012-08-01 Opko Curna Llc Tratamiento de enfermedades relacionadas con lim homeobox 2(lhx2) mediante la inhibicion del transcripto antisentido natural a polinucleotidos lhx2
TW201201819A (en) 2010-05-19 2012-01-16 Opko Curna Llc Treatment of BCL2-like 11 (BCL2L11) related diseases by inhibition of natural antisense transcript to BCL2L11
NO2576784T3 (da) 2010-05-26 2018-04-14
EP3299464B1 (en) 2010-05-26 2019-10-02 CuRNA, Inc. Treatment of atonal homolog 1 (atoh1) related diseases by inhibition of natural antisense transcript to atoh1
US20120004278A1 (en) * 2010-06-18 2012-01-05 The Board Of Trustees Of The Leland Stanford Junior University Linc rnas in cancer diagnosis and treatment
JP5981428B2 (ja) 2010-07-19 2016-08-31 アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． 筋緊張性ジストロフィー・プロテインキナーゼ（ｄｍｐｋ）発現の調整
WO2012018881A2 (en) * 2010-08-03 2012-02-09 Alnylam Pharmaceuticals, Inc. Methods and compositions for the regulation of rna
WO2012065143A1 (en) 2010-11-12 2012-05-18 The General Hospital Corporation Polycomb-associated non-coding rnas
EP2655621B1 (en) 2010-12-20 2018-05-23 The General Hospital Corporation Polycomb-associated non-coding rnas
US9580708B2 (en) 2011-09-14 2017-02-28 Rana Therapeutics, Inc. Multimeric oligonucleotides compounds
WO2013080784A1 (ja) 2011-11-30 2013-06-06 シャープ株式会社 メモリ回路とその駆動方法、及び、これを用いた不揮発性記憶装置、並びに、液晶表示装置

Also Published As

Publication number Publication date
EA201492114A1 (ru) 2015-04-30
EP3511416A1 (en) 2019-07-17
WO2013173652A1 (en) 2013-11-21
EP2850189B8 (en) 2019-01-23
US20150218560A1 (en) 2015-08-06
AU2013262663A1 (en) 2015-01-22
KR20160073885A (ko) 2016-06-27
CN104583398A (zh) 2015-04-29
EP2850189A1 (en) 2015-03-25
EP2850189A4 (en) 2016-01-06
KR102028784B1 (ko) 2019-10-04
CA2873809A1 (en) 2013-11-21
EP2850189B1 (en) 2018-11-07
US20150133362A1 (en) 2015-05-14
JP2015518714A (ja) 2015-07-06

Similar Documents

Publication Publication Date Title
DK2850189T3 (da) Sammensætninger og fremgangsmåder til modulering af genekspression
US11788089B2 (en) Compositions and methods for modulating MECP2 expression
US10059941B2 (en) Compositions and methods for modulating SMN gene family expression
US10174328B2 (en) Compositions and methods for treating amyotrophic lateral sclerosis
US20150141320A1 (en) Compositions and methods for modulating gene expression
US20160122760A1 (en) Compositions and methods for modulating foxp3 expression
US20150159161A1 (en) Compositions and methods for modulating pten expression
KR20180118259A (ko) 표적 세포 내에서 치료적 단백질의 표적화된 생산을 위한 시스템 및 방법
US20150191722A1 (en) Compositions and methods for modulating apoa1 and abca1 expression
EP2849800A1 (en) Compositions and methods for modulating bdnf expression
WO2013173635A1 (en) Compositions and methods for modulating gene expression
US10837014B2 (en) Compositions and methods for modulating SMN gene family expression
US20240050461A1 (en) Use of mirna-485 inhibitors for inducing hair growth