ES2204360T1 - Procedimiento para la inhibicion de la expresion de un gen diana y medicamento para la terapia de una enfermedad tumoral. - Google Patents

Procedimiento para la inhibicion de la expresion de un gen diana y medicamento para la terapia de una enfermedad tumoral.

Info

Publication number
ES2204360T1
ES2204360T1 ES02702247T ES02702247T ES2204360T1 ES 2204360 T1 ES2204360 T1 ES 2204360T1 ES 02702247 T ES02702247 T ES 02702247T ES 02702247 T ES02702247 T ES 02702247T ES 2204360 T1 ES2204360 T1 ES 2204360T1
Authority
ES
Spain
Prior art keywords
dsrna
bcl
medication
thread
strand
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
ES02702247T
Other languages
English (en)
Other versions
ES2204360T3 (es
Inventor
Roland Kreutzer
Stefan Limmer
Hans-Peter Vornlocher
Philipp Hadwiger
Anke Geick
Matthias Ocker
Christoph Herold
Detlef Schuppan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alnylam Europe AG
Original Assignee
Ribopharma AG
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=7669989&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ES2204360(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Ribopharma AG filed Critical Ribopharma AG
Publication of ES2204360T1 publication Critical patent/ES2204360T1/es
Application granted granted Critical
Publication of ES2204360T3 publication Critical patent/ES2204360T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C12N15/1131—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 against viruses
    • 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
    • C12N2310/15—Nucleic acids forming more than 2 strands, e.g. TFOs
    • C12N2310/152—Nucleic acids forming more than 2 strands, e.g. TFOs on a single-stranded target, e.g. fold-back TFOs
    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/318—Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
    • C12N2310/3183—Diol linkers, e.g. glycols or propanediols
    • 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
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • 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
    • C12N2310/3511—Conjugate intercalating or cleaving agent
    • 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
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed

Landscapes

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

Abstract

Procedimiento para la inhibición de una expresión de al menos un gen diana, que inhibe o que impide la apoptosis de una célula tumoral, insertándose al menos un ácido ribonucleico (dsRNA) de doble hebra en la célula tumoral, una de cuyas hebras S1 presenta una zona complementaria con el gen diana al menos por tamos, constituida por menos de 25 nucleótidos sucesivos.

Description

PROTOCOLO DE SECUENCIAS
<110> Ribipharma AG
<120> Medicamento tumoral
<130> 412012GA
<140>
<141>
<160> 6
<170> PatentIn Ver. 2.1
<210> 1
<211> 22
<212> RNA
<213> Secuencia sintética
<220>
<223> Descripción de la secuencia sintética: sentido-hebra de un dsRNA complementario de una secuencia del gen Bcl-2 humano
<400> 1
caggaccucg ccgcugcaga cc 
\hfill
22
<210> 2
<211> 24
<212> RNA
<213> Secuencia sintética
<220>
<223> Descripción de la secuencia sintética: antisentido-hebra de un dsRNA complementario de una secuencia del gen Bcl-2 humano
<400> 2
ggucugcagc ggcgaggucc uggc 
\hfill
24
<210> 3
<211> 22
<212> RNA
<213> Secuencia sintética
<220>
<223> Descripción de la secuencia sintética: sentido-hebra de un dsRNA complementario de una secuencia del gen Bcl-2 humano
<400> 3
gccuuugugg aacuguacgg cc 
\hfill
22
<210> 4
<211> 24
<212> RNA
<213> Secuencia sintética
<220>
<223> Descripción de la secuencia sintética: antisentido-hebra de un dsRNA complementario de una secuencia del gen Bcl-2 humano
<400> 4
ggccguacag uuccacaaag gcau 
\hfill
24
<210> 5
<211> 22
<212> RNA
<213> Secuencia sintética
<220>
<223> Descripción de la secuencia sintética: sentido-hebra de un dsRNA complementario de una secuencia del gen de resistencia a la neomicina
<400> 5
caaggaugag gaucguuucg ca 
\hfill
22
<210> 6
<211> 23
<212> RNA
<213> Secuencia sintética
<220>
<223> Descripción de la secuencia sintética: antisentido-hebra de un dsRNA complementario de una secuencia de un gen de resistencia a la neomicina
<400> 6
gcgaaacgau ccucauccug ucu 
\hfill
23

Claims (26)

1. Procedimiento para la inhibición de una expresión de al menos un gen diana, que inhibe o que impide la apoptosis de una célula tumoral, insertándose al menos un ácido ribonucleico (dsRNA) de doble hebra en la célula tumoral, una de cuyas hebras S1 presenta una zona complementaria con el gen diana al menos por tamos, constituida por menos de 25 nucleótidos sucesivos.
2. Procedimiento según la reivindicación 1, en el que al menos un extremo del dsRNA presenta una transición de hebra única, constituida por 1 hasta 4, especialmente por 2 o 3 nucleótidos.
3. Procedimiento según una de las reivindicaciones precedentes, en el que la transición de hebra única se encuentra en el extremo 3' de la hebra S1.
4. Procedimiento según una de las reivindicaciones precedentes, en el que el dsRNA presenta una transición de hebra única solamente en un extremo, especialmente en el que está situado en el extremo 3' de la hebra S1.
5. Procedimiento según una de las reivindicaciones precedentes, en el que la zona complementaria del dsRNA presenta desde 19 hasta 24, preferentemente desde 21 hasta 23, especialmente 22 nucleótidos.
6. Procedimiento según una de las reivindicaciones precedentes, en el que la hebra S1 presenta menos de 30, preferentemente menos de 25, de forma especialmente preferente desde 21 hasta 24 nucleótidos.
7. Procedimiento según una de las reivindicaciones precedentes, en el que se modifica al menos uno de los extremos del dsRNA para contrarrestar una degradación en la célula tumoral o una disociación.
8. Procedimiento según una de las reivindicaciones precedentes, en el que se aumenta la cohesión del dsRNA, provocada por pares de nucleótidos complementarios, mediante al menos otro, preferentemente mediante otros dos enlaces químicos.
9. Procedimiento según una de las reivindicaciones precedentes, en el que el gen diana es, al menos, un gen de la familia Bcl-2, especialmente Bcl-2, Bcl-w o Bcl-Xl o son tanto Bcl-2 como Bcl-xL.
10. Procedimiento según una de las reivindicaciones precedentes, en el que el dsRNA está constituido por una hebra S2 con la secuencia SEQ ID NO: 1 y por la hebra S1 con la secuencia SEQ ID NO: 2 o por una hebra S2 con la secuencia SEQ ID NO: 3 y por la hebra S1 con la secuencia SEQ ID NO: 4 según el protocolo de secuencias adjunto.
11. Procedimiento según una de las reivindicaciones precedentes, en el que la célula tumoral es una célula de carcinoma del páncreas.
12. Procedimiento según una de las reivindicaciones precedentes, en el que el dsRNA se inserta en la célula tumoral por medio de una estructura micelar que rodea al dsRNA, preferentemente un liposoma, o una cápside que rodea al dsRNA.
13. Medicamento para la terapia de una enfermedad tumoral, que contiene al menos un ácido ribonucléico de doble hebra (dsRNA) para la inhibición de una expresión de al menos un gen diana, que inhibe o que impide la apoptosis de células tumorales, presentando una hebra S1 del dsRNA una zona complementaria con el gen diana, al menos por tamos, constituida por menos de 25 nucleótidos sucesivos.
14. Medicamento según la reivindicación 13, en el que al menos un extremo del dsRNA presenta una transición de hebra única, constituida por 1 hasta 4, especialmente por 2 o 3 nucleótidos.
15. Medicamento según las reivindicaciones 13 o 14, en el que la transición de hebra única se encuentra en el extremo 3' de la hebra S1.
16. Medicamento según las reivindicaciones 13 a 15, en el que el dsRNA presenta una transición de hebra única solamente en un extremo, especialmente en el que está situado en el extremo 3' de la hebra S1.
17. Medicamento según las reivindicaciones 13 a 16, en el que la zona complementaria del dsRNA presenta desde 19 hasta 24, preferentemente desde 21 hasta 23, especialmente 22 nucleótidos.
18. Medicamento según las reivindicaciones 13 a 17, en el que la hebra S1 presenta menos de 30, preferentemente menos de 25, de forma especialmente preferente desde 21 hasta 24 nucleótidos.
19. Medicamento según las reivindicaciones 13 a 18, en el que está modificado al menos uno de los extremos del dsRNA para contrarrestar una degradación en la célula tumoral o una disociación.
20. Medicamento según las reivindicaciones 13 a 19, en el que está aumentada la cohesión del dsRNA, provocada por pares de nucleótidos complementarios, mediante al menos otro, preferentemente mediante otros dos enlaces químicos.
21. Medicamento según las reivindicaciones 13 a 20, en el que el gen diana es, al menos, un gen de la familia Bcl-2, especialmente Bcl-2, Bcl-w o Bcl-xL o son tanto Bcl-2 como Bcl-xL.
22. Medicamento según las reivindicaciones 13 a 21, en el que el dsRNA está constituido por una hebra S2 con la secuencia SEQ ID NO: 1 y por la hebra S1 con la secuencia SEQ ID NO: 2 o por una hebra S2 con la secuencia SEQ ID NO: 3 y por la hebra S1 con la secuencia SEQ ID NO: 4 según el protocolo de secuencias adjunto.
23. Medicamento según las reivindicaciones 13 a 22, en el que la célula tumoral es una célula de carcinoma del páncreas.
24. Medicamento según las reivindicaciones 13 a 23, en el que el dsRNA se presenta en el medicamento en una solución o rodeado por una estructura micelar que rodea al dsRNA, preferentemente un liposoma, o por una cápside.
25. Medicamento según las reivindicaciones 13 a 24, en el que el medicamento presenta una preparación, que es adecuada para inhalación, ingestión oral o por inyección, especialmente para la inyección intravenosa o intraperitoneal o para inyección directa en un tejido tumoral.
26. Medicamento según la reivindicación 25, en el que la preparación está constituida por un tampón fisiológicamente compatible, especialmente una solución salina tamponada la fosfato, y por el dsRNA.
ES02702247T 2001-01-09 2002-01-09 Procedimiento para la inhibicion de la expresion de un gen diana y medicamento para la terapia de una enfermedad tumoral. Expired - Lifetime ES2204360T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10100586A DE10100586C1 (de) 2001-01-09 2001-01-09 Verfahren zur Hemmung der Expression eines Ziegens
DE10100586 2001-01-09

Publications (2)

Publication Number Publication Date
ES2204360T1 true ES2204360T1 (es) 2004-05-01
ES2204360T3 ES2204360T3 (es) 2010-07-06

Family

ID=7669989

Family Applications (1)

Application Number Title Priority Date Filing Date
ES02702247T Expired - Lifetime ES2204360T3 (es) 2001-01-09 2002-01-09 Procedimiento para la inhibicion de la expresion de un gen diana y medicamento para la terapia de una enfermedad tumoral.

Country Status (10)

Country Link
US (1) US7473525B2 (es)
EP (3) EP2213736B1 (es)
JP (1) JP4209678B2 (es)
CN (1) CN1650010A (es)
AT (1) ATE460481T1 (es)
CA (1) CA2432341A1 (es)
DE (2) DE10100586C1 (es)
ES (1) ES2204360T3 (es)
WO (1) WO2002055692A2 (es)
ZA (2) ZA200304127B (es)

Families Citing this family (188)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040203024A1 (en) * 1996-06-06 2004-10-14 Baker Brenda F. Modified oligonucleotides for use in RNA interference
US20050053976A1 (en) * 1996-06-06 2005-03-10 Baker Brenda F. Chimeric oligomeric compounds and their use in gene modulation
US7812149B2 (en) * 1996-06-06 2010-10-12 Isis Pharmaceuticals, Inc. 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations
US9096636B2 (en) 1996-06-06 2015-08-04 Isis Pharmaceuticals, Inc. Chimeric oligomeric compounds and their use in gene modulation
US20040147022A1 (en) * 1996-06-06 2004-07-29 Baker Brenda F. 2'-methoxy substituted oligomeric compounds and compositions for use in gene modulations
US5898031A (en) * 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US20050042647A1 (en) * 1996-06-06 2005-02-24 Baker Brenda F. Phosphorous-linked oligomeric compounds and their use in gene modulation
US20050119470A1 (en) * 1996-06-06 2005-06-02 Muthiah Manoharan Conjugated oligomeric compounds and their use in gene modulation
US20040171031A1 (en) * 1996-06-06 2004-09-02 Baker Brenda F. Sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
CA2361201A1 (en) 1999-01-28 2000-08-03 Medical College Of Georgia Research Institute, Inc. Composition and method for in vivo and in vitro attenuation of gene expression using double stranded rna
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
US7601494B2 (en) 1999-03-17 2009-10-13 The University Of North Carolina At Chapel Hill Method of screening candidate compounds for susceptibility to biliary excretion
DE10100586C1 (de) 2001-01-09 2002-04-11 Ribopharma Ag Verfahren zur Hemmung der Expression eines Ziegens
US7829693B2 (en) 1999-11-24 2010-11-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of a target gene
US8202979B2 (en) 2002-02-20 2012-06-19 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid
WO2003070918A2 (en) 2002-02-20 2003-08-28 Ribozyme Pharmaceuticals, Incorporated Rna interference by modified short interfering nucleic acid
JP2003526367A (ja) * 2000-03-16 2003-09-09 ジェネティカ インコーポレイテッド Ｒｎａ干渉の方法とｒｎａ干渉組成物
US8202846B2 (en) * 2000-03-16 2012-06-19 Cold Spring Harbor Laboratory Methods and compositions for RNA interference
EP2345742B1 (en) 2000-03-30 2014-06-11 The Whitehead Institute for Biomedical Research RNA sequence-specific mediators of RNA interference
ES2728168T3 (es) 2000-12-01 2019-10-22 Max Planck Gesellschaft Moléculas pequeñas de ARN que median en la interferencia de ARN
EP2264173A3 (de) 2001-01-09 2015-01-14 Alnylam Europe AG Verwendung einer doppelsträngigen Ribonukleinsäure zur gezielten Hemmung der Expression eines vorgegebenen Zielgens
WO2003035869A1 (de) * 2001-10-26 2003-05-01 Ribopharma Ag Verwendung einer doppelsträngigen ribonukleinsäure zur gezielten hemmung der expression eines vorgegebenen zielgens
US7423142B2 (en) * 2001-01-09 2008-09-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of anti-apoptotic genes
US7767802B2 (en) * 2001-01-09 2010-08-03 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of anti-apoptotic genes
US8546143B2 (en) 2001-01-09 2013-10-01 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of a target gene
US20050158735A1 (en) * 2001-05-18 2005-07-21 Sirna Therapeutics, Inc. RNA interference mediated inhibition of proliferating cell nuclear antigen (PCNA) gene expression using short interfering nucleic acid (siNA)
US20040019001A1 (en) * 2002-02-20 2004-01-29 Mcswiggen James A. RNA interference mediated inhibition of protein typrosine phosphatase-1B (PTP-1B) gene expression using short interfering RNA
US20050203040A1 (en) * 2001-05-18 2005-09-15 Sirna Therapeutics, Inc. RNA interference mediated inhibition of vascular cell adhesion molecule (VCAM) gene expression using short interfering nucleic acid (siNA)
US20050176025A1 (en) * 2001-05-18 2005-08-11 Sirna Therapeutics, Inc. RNA interference mediated inhibition of B-cell CLL/Lymphoma-2 (BCL-2) gene expression using short interfering nucleic acid (siNA)
US20050143333A1 (en) * 2001-05-18 2005-06-30 Sirna Therapeutics, Inc. RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (SINA)
US20050124566A1 (en) * 2001-05-18 2005-06-09 Sirna Therapeutics, Inc. RNA interference mediated inhibition of myostatin gene expression using short interfering nucleic acid (siNA)
US20050288242A1 (en) * 2001-05-18 2005-12-29 Sirna Therapeutics, Inc. RNA interference mediated inhibition of RAS gene expression using short interfering nucleic acid (siNA)
US20050196767A1 (en) * 2001-05-18 2005-09-08 Sirna Therapeutics, Inc. RNA interference mediated inhibition of GRB2 associated binding protein (GAB2) gene expression using short interfering nucleic acis (siNA)
US20050196765A1 (en) * 2001-05-18 2005-09-08 Sirna Therapeutics, Inc. RNA interference mediated inhibition of checkpoint Kinase-1 (CHK-1) gene expression using short interfering nucleic acid (siNA)
US20050182007A1 (en) * 2001-05-18 2005-08-18 Sirna Therapeutics, Inc. RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (SINA)
US9994853B2 (en) 2001-05-18 2018-06-12 Sirna Therapeutics, Inc. Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference
US20050159381A1 (en) * 2001-05-18 2005-07-21 Sirna Therapeutics, Inc. RNA interference mediated inhibition of chromosome translocation gene expression using short interfering nucleic acid (siNA)
US20050148530A1 (en) 2002-02-20 2005-07-07 Sirna Therapeutics, Inc. RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
US20050233997A1 (en) * 2001-05-18 2005-10-20 Sirna Therapeutics, Inc. RNA interference mediated inhibition of matrix metalloproteinase 13 (MMP13) gene expression using short interfering nucleic acid (siNA)
WO2005078097A2 (en) 2004-02-10 2005-08-25 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING MULTIFUNCTIONAL SHORT INTERFERING NUCLEIC ACID (Multifunctional siNA)
US20050159382A1 (en) * 2001-05-18 2005-07-21 Sirna Therapeutics, Inc. RNA interference mediated inhibition of polycomb group protein EZH2 gene expression using short interfering nucleic acid (siNA)
EP1412371B1 (en) 2001-07-12 2016-02-24 University of Massachusetts IN VIVO PRODUCTION OF SMALL INTERFERING RNAs THAT MEDIATE GENE SILENCING
ES2546829T3 (es) 2001-07-23 2015-09-29 The Board Of Trustees Of The Leland Stanford Junior University Métodos y composiciones para la inhibición mediada por iARN de la expresión génica en mamíferos
US10590418B2 (en) * 2001-07-23 2020-03-17 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for RNAi mediated inhibition of gene expression in mammals
US7745418B2 (en) 2001-10-12 2010-06-29 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting viral replication
DE10163098B4 (de) 2001-10-12 2005-06-02 Alnylam Europe Ag Verfahren zur Hemmung der Replikation von Viren
FR2832154B1 (fr) 2001-11-09 2007-03-16 Centre Nat Rech Scient Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene
JP4242590B2 (ja) 2002-01-11 2009-03-25 俊一 塩澤 慢性関節リウマチの疾患感受性遺伝子、及びその利用
DE10202419A1 (de) 2002-01-22 2003-08-07 Ribopharma Ag Verfahren zur Hemmung der Expression eines durch eine Chromosomen-Aberration entstandenen Zielgens
EP2213292B2 (en) 2002-02-01 2016-06-22 Life Technologies Corporation Double-stranded oligonucleotides
US9657294B2 (en) 2002-02-20 2017-05-23 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US9181551B2 (en) 2002-02-20 2015-11-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
AU2003207708A1 (en) 2002-02-20 2003-09-09 Sirna Therapeutics, Inc. Rna interference mediated inhibition of map kinase genes
CA2463595A1 (en) * 2002-02-20 2003-08-28 Sirna Therapeutics, Inc. Rna interference mediated inhibition of bcl2 gene expression using short interfering nucleic acid (sina)
US7399586B2 (en) 2002-05-23 2008-07-15 Ceptyr, Inc. Modulation of biological signal transduction by RNA interference
US20050245492A1 (en) 2004-04-28 2005-11-03 Lephart Edwin D Use of equol for treating skin diseases
US7148342B2 (en) 2002-07-24 2006-12-12 The Trustees Of The University Of Pennyslvania Compositions and methods for sirna inhibition of angiogenesis
EP1572956A2 (en) 2002-08-01 2005-09-14 City of Hope Methods and kits for synthesis of sirna expression cassettes
US20080274989A1 (en) 2002-08-05 2008-11-06 University Of Iowa Research Foundation Rna Interference Suppression of Neurodegenerative Diseases and Methods of Use Thereof
US20050042646A1 (en) 2002-08-05 2005-02-24 Davidson Beverly L. RNA interference suppresion of neurodegenerative diseases and methods of use thereof
US20040241854A1 (en) 2002-08-05 2004-12-02 Davidson Beverly L. siRNA-mediated gene silencing
WO2004014933A1 (en) 2002-08-07 2004-02-19 University Of Massachusetts Compositions for rna interference and methods of use thereof
US7892793B2 (en) 2002-11-04 2011-02-22 University Of Massachusetts Allele-specific RNA interference
WO2004044132A2 (en) * 2002-11-05 2004-05-27 Isis Pharmaceuticals, Inc. Modified oligonucleotides for use in rna interference
JP4526228B2 (ja) * 2002-11-22 2010-08-18 隆 森田 ＲＮＡｉによる新規治療法および治療剤
US20040248299A1 (en) * 2002-12-27 2004-12-09 Sumedha Jayasena RNA interference
GB0306148D0 (en) * 2003-03-18 2003-04-23 Milner Jo Regulation of gene expression
CA2520181A1 (en) * 2003-03-26 2004-10-14 Astral Inc. Selected rna motifs to include cell death and/or apoptosis
EP1640452A4 (en) * 2003-05-30 2009-12-23 Nippon Shinyaku Co Ltd OLIGOBICATENARY RNA INHIBITING BCL-2 EXPRESSION AND MEDICINAL COMPOSITION CONTAINING THE SAME
WO2004105774A1 (ja) * 2003-05-30 2004-12-09 Nippon Shinyaku Co., Ltd. オリゴ核酸担持複合体、当該複合体を含有する医薬組成物
WO2005001043A2 (en) 2003-06-02 2005-01-06 University Of Massachusetts METHODS AND COMPOSITIONS FOR ENHANCING THE EFFICACY AND SPECIFICITY OF FNAi
US7750144B2 (en) 2003-06-02 2010-07-06 University Of Massachusetts Methods and compositions for enhancing the efficacy and specificity of RNA silencing
PL1633767T3 (pl) 2003-06-02 2019-07-31 University Of Massachusetts Sposoby i kompozycje do kontrolowania wydajności wyciszania rna
EP1486564A1 (de) * 2003-06-13 2004-12-15 Ribopharma AG SiRNA mit erhöhter Stabilität in Serum
EP1633770B1 (en) 2003-06-13 2015-04-29 Alnylam Europe AG Double-stranded ribonucleic acid with increased effectiveness in an organism
EP1636342A4 (en) * 2003-06-20 2008-10-08 Isis Pharmaceuticals Inc OLIGOMERIC COMPOUNDS FOR GENE MODULATION
ITRM20030335A1 (it) * 2003-07-09 2005-01-10 Univ Roma Sistema di espressione di sirna.
EP2821085B1 (en) 2003-09-12 2020-04-29 University of Massachusetts Rna interference for the treatment of gain-of-function disorders
US8680063B2 (en) 2003-09-12 2014-03-25 University Of Massachusetts RNA interference for the treatment of gain-of-function disorders
US20060134787A1 (en) 2004-12-22 2006-06-22 University Of Massachusetts Methods and compositions for enhancing the efficacy and specificity of single and double blunt-ended siRNA
WO2005078848A2 (en) 2004-02-11 2005-08-25 University Of Tennessee Research Foundation Inhibition of tumor growth and invasion by anti-matrix metalloproteinase dnazymes
US8569474B2 (en) * 2004-03-09 2013-10-29 Isis Pharmaceuticals, Inc. Double stranded constructs comprising one or more short strands hybridized to a longer strand
EP2899278A1 (en) 2004-03-12 2015-07-29 Alnylam Pharmaceuticals Inc. iRNA agents targeting VEGF
AU2005238034A1 (en) 2004-04-23 2005-11-10 The Trustees Of Columbia University In The City Of New York Inhibition of hairless protein mRNA
US10508277B2 (en) 2004-05-24 2019-12-17 Sirna Therapeutics, Inc. Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference
EP2290074B1 (en) 2004-05-28 2014-12-17 Asuragen, Inc. Methods and compositions involving microRNA
JP2008501693A (ja) * 2004-06-03 2008-01-24 アイシス ファーマシューティカルズ、インク． 遺伝子調節で使用するための個別に調節された鎖を有する二本鎖組成物
US8394947B2 (en) * 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
EP2484780A1 (en) 2004-07-23 2012-08-08 The University of North Carolina At Chapel Hill Methods and materials for determining pain sensibility and predicting and treating related disorders
US20060040391A1 (en) * 2004-08-20 2006-02-23 Promega Corporation RNA interference vectors
WO2006022325A1 (ja) 2004-08-26 2006-03-02 Nippon Shinyaku Co., Ltd. ガラクトース誘導体、薬物担体及び医薬組成物
US7884086B2 (en) * 2004-09-08 2011-02-08 Isis Pharmaceuticals, Inc. Conjugates for use in hepatocyte free uptake assays
WO2006035432A2 (en) * 2004-09-27 2006-04-06 Tel Hashomer Medical Research Infrastructure And Services Ltd. Gene silencing for use in dermatology
EP2287303B1 (en) 2004-11-12 2014-07-02 Asuragen, Inc. Methods and compositions involving miRNA and miRNA inhibitor molecules
US8703769B2 (en) 2005-07-15 2014-04-22 The University Of North Carolina At Chapel Hill Use of EGFR inhibitors to prevent or treat obesity
WO2007022470A2 (en) 2005-08-18 2007-02-22 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating neurological disease
CA2620387C (en) 2005-09-20 2018-09-18 Basf Plant Science Gmbh Methods for controlling gene expression using ta-sirna
EP1934348B1 (en) 2005-10-11 2018-05-02 Ben-Gurion University Of The Negev Research And Development Authority Compositions for silencing the expression of vdac1 and uses thereof
US7320965B2 (en) 2005-10-28 2008-01-22 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of Huntingtin gene
AU2006311725B2 (en) 2005-11-04 2011-11-24 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of NAV1.8 gene
EP2363134B1 (en) 2005-11-09 2014-01-08 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of factor V Leiden mutant gene
CA2638797A1 (en) 2006-03-01 2007-09-07 Nippon Shinyaku Co., Ltd. Galactose derivative, drug carrier and medicinal composition
FR2898908A1 (fr) 2006-03-24 2007-09-28 Agronomique Inst Nat Rech Procede de preparation de cellules aviaires differenciees et genes impliques dans le maintien de la pluripotence
NZ571568A (en) 2006-03-31 2010-11-26 Alnylam Pharmaceuticals Inc Double-stranded RNA molecule compositions and methods for inhibiting expression of Eg5 gene
CN101484588B (zh) 2006-05-11 2013-11-06 阿尔尼拉姆医药品有限公司 抑制pcsk9基因表达的组合物和方法
EP2392583A1 (en) 2006-05-19 2011-12-07 Alnylam Europe AG. RNAi modulation of Aha and therapeutic uses thereof
CA2653451C (en) 2006-05-22 2015-12-29 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of ikk-b gene
US8598333B2 (en) 2006-05-26 2013-12-03 Alnylam Pharmaceuticals, Inc. SiRNA silencing of genes expressed in cancer
WO2008036638A2 (en) 2006-09-18 2008-03-27 Alnylam Pharmaceuticals, Inc. Rnai modulation of scap and therapeutic uses thereof
CA2663878A1 (en) * 2006-09-19 2008-03-27 Asuragen, Inc. Mir-200 regulated genes and pathways as targets for therapeutic intervention
CA2663962A1 (en) * 2006-09-19 2008-03-27 Asuragen, Inc. Mir-15, mir-26, mir-31,mir-145, mir-147, mir-188, mir-215, mir-216, mir-331, mmu-mir-292-3p regulated genes and pathways as targets for therapeutic intervention
CA2663581C (en) 2006-09-21 2016-03-01 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the hamp gene
CA2671299A1 (en) * 2006-12-08 2008-06-19 Asuragen, Inc. Functions and targets of let-7 micro rnas
CN101622350A (zh) * 2006-12-08 2010-01-06 奥斯瑞根公司 作为干预治疗靶标的miR-126调控基因和通路
AU2007333107A1 (en) * 2006-12-08 2008-06-19 Asuragen, Inc. miR-21 regulated genes and pathways as targets for therapeutic intervention
JP2010516786A (ja) 2007-01-26 2010-05-20 ユニバーシティー オブ ルイヴィル リサーチ ファウンデーション，インコーポレーテッド ワクチンとしての使用のためのエキソソーム成分の改変
AU2008228814B2 (en) 2007-03-21 2014-03-06 Brookhaven Science Associates, Llc Combined hairpin-antisense compositions and methods for modulating expression
PE20090064A1 (es) 2007-03-26 2009-03-02 Novartis Ag Acido ribonucleico de doble cadena para inhibir la expresion del gen e6ap humano y composicion farmaceutica que lo comprende
US7759320B2 (en) 2007-03-29 2010-07-20 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of a gene from the Ebola
US20090131354A1 (en) * 2007-05-22 2009-05-21 Bader Andreas G miR-126 REGULATED GENES AND PATHWAYS AS TARGETS FOR THERAPEUTIC INTERVENTION
US20090232893A1 (en) * 2007-05-22 2009-09-17 Bader Andreas G miR-143 REGULATED GENES AND PATHWAYS AS TARGETS FOR THERAPEUTIC INTERVENTION
US20090227533A1 (en) * 2007-06-08 2009-09-10 Bader Andreas G miR-34 Regulated Genes and Pathways as Targets for Therapeutic Intervention
CA2692503C (en) 2007-07-05 2013-09-24 Novartis Ag Dsrna for treating viral infection
EP2198050A1 (en) * 2007-09-14 2010-06-23 Asuragen, INC. Micrornas differentially expressed in cervical cancer and uses thereof
US20100280097A1 (en) * 2007-09-18 2010-11-04 Intradigm Corporation Compositions comprising hif-1 alpha sirna and methods of use thereof
JP2010538678A (ja) * 2007-09-18 2010-12-16 イントラドイグム コーポレーション Ｋ−ｒａｓｓｉＲＮＡ含有組成物及びそれらの使用法
US8071562B2 (en) * 2007-12-01 2011-12-06 Mirna Therapeutics, Inc. MiR-124 regulated genes and pathways as targets for therapeutic intervention
JP5530933B2 (ja) 2007-12-10 2014-06-25 アルナイラム ファーマシューティカルズ， インコーポレイテッド 第ｖｉｉ因子遺伝子発現阻害のための組成物及び方法
US20090192114A1 (en) * 2007-12-21 2009-07-30 Dmitriy Ovcharenko miR-10 Regulated Genes and Pathways as Targets for Therapeutic Intervention
US20090263803A1 (en) * 2008-02-08 2009-10-22 Sylvie Beaudenon Mirnas differentially expressed in lymph nodes from cancer patients
AU2009221775B2 (en) 2008-03-05 2015-05-07 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of Eg5 and VEGF genes
EP2268832A2 (en) * 2008-03-06 2011-01-05 Asuragen, INC. Microrna markers for recurrence of colorectal cancer
CA2717496A1 (en) * 2008-03-12 2009-09-17 Intradigm Corporation Compositions comprising notch1 sirna and methods of use thereof
EP2271757A2 (en) * 2008-03-26 2011-01-12 Asuragen, INC. Compositions and methods related to mir-16 and therapy of prostate cancer
US20090258928A1 (en) * 2008-04-08 2009-10-15 Asuragen, Inc. Methods and compositions for diagnosing and modulating human papillomavirus (hpv)
US20110166198A1 (en) * 2008-04-10 2011-07-07 Alnylam Pharmaceuticals, Inc. Rna compositions for modulating immune response
US8258111B2 (en) * 2008-05-08 2012-09-04 The Johns Hopkins University Compositions and methods related to miRNA modulation of neovascularization or angiogenesis
EP2293800B1 (en) 2008-06-06 2016-10-05 Quark Pharmaceuticals, Inc. Compositions and methods for treatment of ear disorders
EP2323695B1 (en) 2008-08-19 2018-12-05 Nektar Therapeutics Complexes of small-interfering nucleic acids
WO2010028054A1 (en) 2008-09-02 2010-03-11 Alnylam Europe Ag. Compositions and methods for inhibiting expression of mutant egfr gene
CA2739170A1 (en) 2008-09-25 2010-04-01 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of serum amyloid a gene
ES2656516T3 (es) 2008-10-20 2018-02-27 Alnylam Pharmaceuticals, Inc. Composiciones y métodos para inhibir la expresión de transtiretina
US20100179213A1 (en) * 2008-11-11 2010-07-15 Mirna Therapeutics, Inc. Methods and Compositions Involving miRNAs In Cancer Stem Cells
US8470792B2 (en) 2008-12-04 2013-06-25 Opko Pharmaceuticals, Llc. Compositions and methods for selective inhibition of VEGF
AU2009324534B2 (en) 2008-12-10 2015-07-30 Alnylam Pharmaceuticals, Inc. GNAQ targeted dsRNA compositions and methods for inhibiting expression
WO2010099341A1 (en) 2009-02-26 2010-09-02 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of mig-12 gene
CN102421900B (zh) 2009-03-12 2015-07-22 阿尔尼拉姆医药品有限公司 用于抑制Eg5和VEGF基因表达的脂质配制的组合物以及方法
FR2944437B1 (fr) * 2009-04-16 2013-05-10 Oreal Utilisation d'inhibiteurs de l'expression d'hif 1 alpha pour proteger la peau des dommages deleteres induits par le rayonnement uva
WO2010141511A2 (en) 2009-06-01 2010-12-09 Halo-Bio Rnai Therapeutics, Inc. Polynucleotides for multivalent rna interference, compositions and methods of use thereof
WO2010147992A1 (en) 2009-06-15 2010-12-23 Alnylam Pharmaceuticals, Inc. Methods for increasing efficacy of lipid formulated sirna
WO2010148013A2 (en) 2009-06-15 2010-12-23 Alnylam Pharmaceuticals, Inc. Lipid formulated dsrna targeting the pcsk9 gene
AP3574A (en) 2009-08-14 2016-02-08 Alnylam Pharmaceuticals Inc Lipid formulated compositions and methods for inhibiting expression of a gene from the ebola virus
US8916693B2 (en) 2009-09-17 2014-12-23 Nektar Therapeutics Monoconjugated chitosans as delivery agents for small interfering nucleic acids
JP5574258B2 (ja) 2009-10-01 2014-08-20 学校法人東京女子医科大学 膵臓がん治療用の組成物
AR079494A1 (es) 2009-12-18 2012-02-01 Novartis Ag Composiciones organicas para tratar las enfermedades relacionadas con el factor de choque por calor 1 hsf1
WO2011098449A1 (en) 2010-02-10 2011-08-18 Novartis Ag Methods and compounds for muscle growth
CA2792291A1 (en) 2010-03-29 2011-10-06 Kumamoto University Sirna therapy for transthyretin (ttr) related ocular amyloidosis
JP2013523162A (ja) 2010-04-06 2013-06-17 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ｃｄ２７４／ｐｄ−ｌ１遺伝子の発現を阻害するための組成物および方法
WO2011153323A2 (en) 2010-06-02 2011-12-08 Alnylam Pharmaceuticals, Inc. Compositions and methods directed to treating liver fibrosis
WO2012027206A1 (en) 2010-08-24 2012-03-01 Merck Sharp & Dohme Corp. SINGLE-STRANDED RNAi AGENTS CONTAINING AN INTERNAL, NON-NUCLEIC ACID SPACER
EP2433644A1 (en) 2010-09-22 2012-03-28 IMBA-Institut für Molekulare Biotechnologie GmbH Breast cancer therapeutics
AR083445A1 (es) 2010-10-14 2013-02-27 Univ Mie siARN CONTRA LA FIBROSIS
EP3327125B1 (en) 2010-10-29 2020-08-05 Sirna Therapeutics, Inc. Rna interference mediated inhibition of gene expression using short interfering nucleic acids (sina)
CN103370054A (zh) 2010-11-09 2013-10-23 阿尔尼拉姆医药品有限公司 用于抑制Eg5和VEGF基因的表达的脂质配制的组合物和方法
CA3191066A1 (en) 2011-06-21 2012-12-27 Alnylam Pharmaceuticals Inc. Compositions and methods for inhibition of expression of apolipoprotein c-iii (apoc3) genes
EP2723861A4 (en) 2011-06-21 2014-12-10 Alnylam Pharmaceuticals Inc COMPOSITIONS AND METHODS FOR INHIBITING HEPCIDINE ANTIMICROBIAL PEPTIDE (HAMP) OR THE ASSOCIATED GENE EXPRESSION
WO2012177906A1 (en) 2011-06-21 2012-12-27 Alnylam Pharmaceuticals, Inc. Assays and methods for determining activity of a therapeutic agent in a subject
EP3597750B1 (en) 2011-06-23 2022-05-04 Alnylam Pharmaceuticals, Inc. Serpina1 sirnas: compositions of matter and methods of treatment
US9644241B2 (en) 2011-09-13 2017-05-09 Interpace Diagnostics, Llc Methods and compositions involving miR-135B for distinguishing pancreatic cancer from benign pancreatic disease
BR112014016870A2 (pt) 2012-01-09 2017-06-27 Huesken Dieter composições orgânicas para tratar doenças relacionadas com beta-catenina
EP2700949A1 (en) 2012-08-24 2014-02-26 IMG Institut für medizinische Genomforschung Planungsgesellschaft M.B.H. Use of biliverdin reductase proteins as cancer marker
EP3699592A1 (en) 2013-03-13 2020-08-26 Geneweave Biosciences Inc. Non-replicative transduction particles and transduction particle-based reporter systems
BR112015026702A2 (pt) 2013-04-21 2018-02-06 Yeda Res And Developmente Co Ltd métodos de extermínio de células senescentes
CN106103475B (zh) 2014-03-11 2021-01-12 塞勒克提斯公司 产生同种异体移植相容的t细胞的方法
WO2016077624A1 (en) 2014-11-12 2016-05-19 Nmc, Inc. Transgenic plants with engineered redox sensitive modulation of photosynthetic antenna complex pigments and methods for making the same
US20180345047A1 (en) 2015-02-26 2018-12-06 Yeda Research And Development Co. Ltd. Method of promoting hair growth
US20180036404A1 (en) 2015-03-02 2018-02-08 180 Therapeutics Lp Method of treating a localized fibrotic disorder using a tnf receptor 2 antagonist
MX2018002090A (es) 2015-08-24 2018-09-12 Halo Bio Rnai Therapeutics Inc Nanoparticulas de polinucleótido para modulación de expresión génica y sus usos.
IL310959A (en) 2015-08-25 2024-04-01 Alnylam Pharmaceuticals Inc Methods and preparations for treating a disorder related to the PCSK9 gene
US11072777B2 (en) 2016-03-04 2021-07-27 University Of Louisville Research Foundation, Inc. Methods and compositions for ex vivo expansion of very small embryonic-like stem cells (VSELs)
MA45470A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques kras et leurs utilisations
MA45469A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques de bêta-caténine et leurs utilisations
MA45349A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques egfr et leurs utilisations
MA45328A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Compositions acide nucléique-polypeptide et utilisations de celles-ci
WO2018020012A1 (en) 2016-07-29 2018-02-01 Danmarks Tekniske Universitet Methods for decoupling cell growth from production of biochemicals and recombinant polypeptides
US20200199541A1 (en) 2017-06-16 2020-06-25 Imba - Institut Für Molekulare Biotechnologie Gmbh Blood vessel organoid, methods of producing and using said organoids
CA3083526A1 (en) 2017-12-06 2019-06-13 Andrew John Geall Compositions and methods of treating muscle atrophy and myotonic dystrophy
JP2023537798A (ja) 2020-03-19 2023-09-06 アビディティー バイオサイエンシーズ，インク． 顔面肩甲上腕型筋ジストロフィーを処置するための組成物および方法

Family Cites Families (86)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5190931A (en) 1983-10-20 1993-03-02 The Research Foundation Of State University Of New York Regulation of gene expression by employing translational inhibition of MRNA utilizing interfering complementary MRNA
US5208149A (en) 1983-10-20 1993-05-04 The Research Foundation Of State University Of New York Nucleic acid constructs containing stable stem and loop structures
US4980286A (en) 1985-07-05 1990-12-25 Whitehead Institute For Biomedical Research In vivo introduction and expression of foreign genetic material in epithelial cells
DE3681787D1 (de) 1985-07-05 1991-11-07 Whitehead Biomedical Inst Expression von fremdem genetischem material in epithelzellen.
US5107065A (en) 1986-03-28 1992-04-21 Calgene, Inc. Anti-sense regulation of gene expression in plant cells
US4987071A (en) 1986-12-03 1991-01-22 University Patents, Inc. RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods
US5712257A (en) 1987-08-12 1998-01-27 Hem Research, Inc. Topically active compositions of mismatched dsRNAs
EP0378576B1 (en) 1987-09-11 1995-01-18 Whitehead Institute For Biomedical Research Transduced fibroblasts and uses therefor
ATE110108T1 (de) 1987-12-11 1994-09-15 Whitehead Biomedical Inst Genetische modifizierung von endothelialen zellen.
US5254678A (en) 1987-12-15 1993-10-19 Gene Shears Pty. Limited Ribozymes
JP2917998B2 (ja) 1988-02-05 1999-07-12 ホワイトヘッド・インスティチュート・フォー・バイオメディカル・リサーチ 修飾された肝細胞およびその用途
US5328470A (en) 1989-03-31 1994-07-12 The Regents Of The University Of Michigan Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5212295A (en) 1990-01-11 1993-05-18 Isis Pharmaceuticals Monomers for preparation of oligonucleotides having chiral phosphorus linkages
JP3249516B2 (ja) 1990-10-31 2002-01-21 ソマティクス セラピー コーポレイション 遺伝子治療のためのレトロウイルスのベクター
FR2675803B1 (fr) 1991-04-25 1996-09-06 Genset Sa Oligonucleotides fermes, antisens et sens et leurs applications.
DE69331543T2 (de) 1992-03-05 2002-09-26 Isis Pharmaceutical Inc Kovalent vernetzte oligonukleotide
EP0649467B1 (en) * 1992-07-02 1998-09-16 HYBRIDON, Inc. Self-stabilized oligonucleotides as therapeutic agents
US6423489B1 (en) 1992-09-10 2002-07-23 Isis Pharmaceuticals, Inc. Compositions and methods for treatment of Hepatitis C virus-associated diseases
US6054299A (en) 1994-04-29 2000-04-25 Conrad; Charles A. Stem-loop cloning vector and method
US6166197A (en) 1995-03-06 2000-12-26 Isis Pharmaceuticals, Inc. Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions
US5674683A (en) 1995-03-21 1997-10-07 Research Corporation Technologies, Inc. Stem-loop and circular oligonucleotides and method of using
US5998203A (en) 1996-04-16 1999-12-07 Ribozyme Pharmaceuticals, Inc. Enzymatic nucleic acids containing 5'-and/or 3'-cap structures
DE19631919C2 (de) * 1996-08-07 1998-07-16 Deutsches Krebsforsch Anti-Sinn-RNA mit Sekundärstruktur
US6127533A (en) 1997-02-14 2000-10-03 Isis Pharmaceuticals, Inc. 2'-O-aminooxy-modified oligonucleotides
GB9710475D0 (en) 1997-05-21 1997-07-16 Zeneca Ltd Gene silencing
GB9720148D0 (en) 1997-09-22 1997-11-26 Innes John Centre Innov Ltd Gene silencing materials and methods
US6506559B1 (en) 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
BRPI9908967B1 (pt) 1998-03-20 2017-05-30 Benitec Australia Ltd processos para reprimir, retardar ou de outro modo reduzir a expressão de um gene alvo em uma célula de planta
CA2325344C (en) 1998-04-08 2017-12-05 Commonwealth Scientific And Industrial Research Organisation Methods and means for obtaining modified phenotypes
AR020078A1 (es) 1998-05-26 2002-04-10 Syngenta Participations Ag Metodo para alterar la expresion de un gen objetivo en una celula de planta
GB9827152D0 (en) 1998-07-03 1999-02-03 Devgen Nv Characterisation of gene function using double stranded rna inhibition
US6271358B1 (en) 1998-07-27 2001-08-07 Isis Pharmaceuticals, Inc. RNA targeted 2′-modified oligonucleotides that are conformationally preorganized
US6486299B1 (en) 1998-09-28 2002-11-26 Curagen Corporation Genes and proteins predictive and therapeutic for stroke, hypertension, diabetes and obesity
JP2002527061A (ja) 1998-10-09 2002-08-27 インジーン・インコーポレイテッド ｓｓＤＮＡの酵素的合成
MXPA01003643A (es) 1998-10-09 2003-07-21 Ingene Inc Produccion de adnss in vivo.
CA2361201A1 (en) * 1999-01-28 2000-08-03 Medical College Of Georgia Research Institute, Inc. Composition and method for in vivo and in vitro attenuation of gene expression using double stranded rna
US6200924B1 (en) 1999-01-29 2001-03-13 E. I. Du Pont De Nemours And Company Porous highly fluorinated acidic polymer catalyst
DE19956568A1 (de) * 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
AU781598B2 (en) 1999-04-21 2005-06-02 Alnylam Pharmaceuticals, Inc. Methods and compositions for inhibiting the function of polynucleotide sequences
CZ20014028A3 (cs) 1999-05-10 2002-02-13 Syngenta Participations Ag Způsob regulace exprese virových genů
US6861220B2 (en) 1999-09-08 2005-03-01 Ramot University Authority For Applied Research & Industrial Development Ltd Genetic screening methods
US6569623B1 (en) 1999-09-08 2003-05-27 Ramot University Authority For Applied Research & Industrial Development Ltd. Genetic screening methods
CA2386270A1 (en) 1999-10-15 2001-04-26 University Of Massachusetts Rna interference pathway genes as tools for targeted genetic interference
GB9927444D0 (en) 1999-11-19 2000-01-19 Cancer Res Campaign Tech Inhibiting gene expression
DE10160151A1 (de) 2001-01-09 2003-06-26 Ribopharma Ag Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens
DE10100586C1 (de) 2001-01-09 2002-04-11 Ribopharma Ag Verfahren zur Hemmung der Expression eines Ziegens
RU2164944C1 (ru) 1999-12-09 2001-04-10 Институт молекулярной биологии им. В.А. Энгельгардта РАН Способ изменения генетических свойств организма
GB9930691D0 (en) 1999-12-24 2000-02-16 Devgen Nv Improvements relating to double-stranded RNA inhibition
WO2002081628A2 (en) 2001-04-05 2002-10-17 Ribozyme Pharmaceuticals, Incorporated Modulation of gene expression associated with inflammation proliferation and neurite outgrowth, using nucleic acid based technologies
JP2003526367A (ja) 2000-03-16 2003-09-09 ジェネティカ インコーポレイテッド Ｒｎａ干渉の方法とｒｎａ干渉組成物
WO2001070949A1 (en) 2000-03-17 2001-09-27 Benitec Australia Ltd Genetic silencing
EP2345742B1 (en) * 2000-03-30 2014-06-11 The Whitehead Institute for Biomedical Research RNA sequence-specific mediators of RNA interference
ATE513910T1 (de) 2000-05-30 2011-07-15 Johnson & Johnson Res Pty Ltd Methoden zur gensuppression mithilfe von rnai verstärkenden faktoren
CN1311081C (zh) 2000-08-19 2007-04-18 爱克斯澳迪亚有限公司 干细胞分化
US20030190635A1 (en) 2002-02-20 2003-10-09 Mcswiggen James A. RNA interference mediated treatment of Alzheimer's disease using short interfering RNA
AU2001296333A1 (en) 2000-09-26 2002-04-08 The Burnham Institute Paad domain-containing polypeptides, encoding nucleic acids, and methods of use
WO2002068637A2 (en) 2000-10-20 2002-09-06 Ribozyme Pharmaceuticals, Inc. Nucleic acid-based treatment of diseases or conditions related to west nile virus infection
US20020173478A1 (en) 2000-11-14 2002-11-21 The Trustees Of The University Of Pennsylvania Post-transcriptional gene silencing by RNAi in mammalian cells
ES2728168T3 (es) 2000-12-01 2019-10-22 Max Planck Gesellschaft Moléculas pequeñas de ARN que median en la interferencia de ARN
WO2002061034A2 (en) 2000-12-08 2002-08-08 Invitrogen Corporation Compositions and methods for rapidly generating recombinant nucleic acid molecules
WO2003035869A1 (de) 2001-10-26 2003-05-01 Ribopharma Ag Verwendung einer doppelsträngigen ribonukleinsäure zur gezielten hemmung der expression eines vorgegebenen zielgens
AU2002256990A1 (en) 2001-02-07 2002-09-24 The Burnham Institute Apoptosis modulator bcl-b and methods for making and using same
GB0104948D0 (en) 2001-02-28 2001-04-18 Novartis Res Foundation Novel methods
AU2002258477A1 (en) 2001-03-08 2002-09-24 Advanced Cell Technology, Inc. Use of rna interference for the creation of lineage specific es and other undifferentiated cells and production of differentiated cells in vitro by co-culture
EP1412371B1 (en) 2001-07-12 2016-02-24 University of Massachusetts IN VIVO PRODUCTION OF SMALL INTERFERING RNAs THAT MEDIATE GENE SILENCING
GB0118223D0 (en) 2001-07-26 2001-09-19 Univ Sheffield Stem loop RNA
WO2003012052A2 (en) 2001-07-30 2003-02-13 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Specific inhibition of gene expression by small double stranded rnas
WO2003016572A1 (en) 2001-08-17 2003-02-27 Eli Lilly And Company Oligonucleotide therapeutics for treating hepatitis c virus infections
US7101995B2 (en) 2001-08-27 2006-09-05 Mirus Bio Corporation Compositions and processes using siRNA, amphipathic compounds and polycations
US20030198627A1 (en) 2001-09-01 2003-10-23 Gert-Jan Arts siRNA knockout assay method and constructs
DE10163098B4 (de) 2001-10-12 2005-06-02 Alnylam Europe Ag Verfahren zur Hemmung der Replikation von Viren
JP2005506087A (ja) 2001-10-26 2005-03-03 リボファーマ アーゲー プラス鎖ｒｎａウイルスによる感染症を処置するための２本鎖リボ核酸の使用
WO2003035870A1 (de) 2001-10-26 2003-05-01 Ribopharma Ag Medikament zur behandlung eines pankreaskarzinoms
DE10230996A1 (de) 2001-10-26 2003-07-17 Ribopharma Ag Medikament zur Behandlung eines Pankreaskarzinoms
CN1604783A (zh) 2001-10-26 2005-04-06 里伯药品公司 通过rna干扰治疗纤维化疾病的药物
IL161733A0 (en) 2001-11-02 2005-11-20 Insert Therapeutics Inc Methods and compositions for therapeutic use of rna interference
FR2832154B1 (fr) * 2001-11-09 2007-03-16 Centre Nat Rech Scient Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene
WO2003044161A2 (en) 2001-11-15 2003-05-30 Tularik Inc. Gene amplification and overexpression in cancer
EP1476459A4 (en) 2002-02-20 2005-05-25 Sirna Therapeutics Inc INHIBITION OF EXPRESSION OF THE CHROMOSOME TRANSLOCATION GENE AGENT BY RNA INTERFERENCE USING SHORT INTERFERING NUCLEIC ACID (siNA)
CA2457528C (en) 2002-02-20 2011-07-12 Sirna Therapeutics, Inc. Rna interference mediated inhibition of hepatitis c virus (hcv) gene expression using short interfering nucleic acid (sina)
AU2003207708A1 (en) 2002-02-20 2003-09-09 Sirna Therapeutics, Inc. Rna interference mediated inhibition of map kinase genes
CA2463595A1 (en) 2002-02-20 2003-08-28 Sirna Therapeutics, Inc. Rna interference mediated inhibition of bcl2 gene expression using short interfering nucleic acid (sina)
US20050107316A1 (en) 2002-02-22 2005-05-19 Klaus Strebhardt Agent for inhibiting development or progress of proliferative diseases and especially cancer diseases and pharmaceutical composition containing said agent
US20030180756A1 (en) 2002-03-21 2003-09-25 Yang Shi Compositions and methods for suppressing eukaryotic gene expression
EP2487243A3 (en) 2005-01-07 2013-08-28 Alnylam Pharmaceuticals Inc. RNAI modulation of RSV and therapeutic uses thereof

Also Published As

Publication number Publication date
JP4209678B2 (ja) 2009-01-14
DE10100586C1 (de) 2002-04-11
WO2002055692A2 (de) 2002-07-18
EP1349927A2 (de) 2003-10-08
EP2213736B1 (de) 2018-03-07
DE50214266D1 (de) 2010-04-22
US7473525B2 (en) 2009-01-06
US20040001811A1 (en) 2004-01-01
CA2432341A1 (en) 2002-07-18
JP2004519457A (ja) 2004-07-02
EP2213736A3 (de) 2010-09-01
EP2365075A1 (de) 2011-09-14
ZA200304500B (en) 2003-11-18
CN1650010A (zh) 2005-08-03
WO2002055692A3 (de) 2003-06-12
EP2213736A2 (de) 2010-08-04
ATE460481T1 (de) 2010-03-15
ZA200304127B (en) 2004-05-11
EP1349927B1 (de) 2010-03-10
ES2204360T3 (es) 2010-07-06

Similar Documents

Publication Publication Date Title
ES2204360T1 (es) Procedimiento para la inhibicion de la expresion de un gen diana y medicamento para la terapia de una enfermedad tumoral.
JP7049262B2 (ja) 結合組織成長因子を標的とするｒｎａ複合体を用いた特発性肺胞線維症の治療
US8119608B2 (en) Method and medicament for inhibiting the expression of a given gene
EP2102343B1 (en) Dbait and its standalone uses thereof
US6372427B1 (en) Cooperative oligonucleotides
US11390871B2 (en) SiRNA structures for high activity and reduced off target
CN108024961A (zh) 使用靶向Hsp47和p21的RNAi分子的恶性肿瘤治疗组合物和方法
CA2542942C (en) Nucleic acids useful for triggering tumor cell lethality
SI2929031T1 (en) PCSK9 IRNA assemblies and procedures for their use
KR20120038546A (ko) ＨＩＦ-1 알파의 ｓｉＲＮＡ 억제를 위한 조성물 및 방법
OA12586A (en) Methods of treatment of a bcl-2 disorder using bcl-2 antisence oligomers.
KR20180104075A (ko) IL4Rα, TRPA1, 또는 F2RL1을 표적화하는 RNA 복합체를 사용한 아토피 피부염 및 천식의 치료
JP2019506862A (ja) Ａｎｇｐｔ２およびｐｄｇｆｂを標的化するｒｎａ複合体を用いる血管新生関連疾患の処置
JP2007530431A5 (es)
KR102099718B1 (ko) 악성 흉막 중피종을 치료하기 위한 마이크로ｒｎａ-기반 방법
CN113730593A (zh) 一种增强核酸药物缓释能力的方法
US10538766B2 (en) Methods and compositions for managing vascular conditions
JP2007517498A5 (es)
KR20220169178A (ko) 타겟 유전자 발현을 조절할 수 있는 헤어핀 구조의 핵산 분자 및 이의 용도
RU2008130901A (ru) iPHK-ОПОСРЕДОВАНННОЕ ИНГИБИРОВАНИЕ IGFR ДЛЯ ЛЕЧЕНИЯ ГЛАЗНОГО АНГИОГЕНЕЗА
KR101783444B1 (ko) miR-33-5p 를 이용한 뇌신경세포 보호 물질 스크리닝 방법
US10519447B2 (en) Therapeutic UNA oligomers and uses thereof
US20150038548A1 (en) Oligonucleotide inhibitors of dna methyltransferases and their use in treating diseases
ES2350978T3 (es) Tratamiento del melanoma mediante la reducción de los niveles de clusterina.
CA3093809A1 (en) Combination therapy for ttr amyloidosis