EA015676B1 - Композиции и способы ингибирования экспрессии гена pcsk9 - Google Patents

Композиции и способы ингибирования экспрессии гена pcsk9 Download PDF

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Publication number
EA015676B1
EA015676B1 EA200870528A EA200870528A EA015676B1 EA 015676 B1 EA015676 B1 EA 015676B1 EA 200870528 A EA200870528 A EA 200870528A EA 200870528 A EA200870528 A EA 200870528A EA 015676 B1 EA015676 B1 EA 015676B1
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Prior art keywords
dsrna
pc8k9
gene
sequence
expression
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EA200870528A
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English (en)
Russian (ru)
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EA200870528A1 (ru
Inventor
Памела Тан
Биргит Брамлаге
Мария Франк-Каменетски
Кевин Фитцжеральд
Акин Акинк
Виктор Е. Котелянски
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Элнилэм Фармасьютикалз, Инк.
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Publication of EA200870528A1 publication Critical patent/EA200870528A1/ru
Publication of EA015676B1 publication Critical patent/EA015676B1/ru

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    • C12N15/113Non-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
    • C12N15/1137Non-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 enzymes
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    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-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
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    • C12N2310/00Structure or type of the nucleic acid
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    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate
    • C12N2310/3515Lipophilic moiety, e.g. cholesterol

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  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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EA200870528A 2006-05-11 2007-05-10 Композиции и способы ингибирования экспрессии гена pcsk9 EA015676B1 (ru)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US79945806P 2006-05-11 2006-05-11
US81720306P 2006-06-27 2006-06-27
US84008906P 2006-08-25 2006-08-25
US82991406P 2006-10-18 2006-10-18
US90113407P 2007-02-13 2007-02-13
PCT/US2007/068655 WO2007134161A2 (en) 2006-05-11 2007-05-10 Compositions and methods for inhibiting expression of the pcsk9 gene

Publications (2)

Publication Number Publication Date
EA200870528A1 EA200870528A1 (ru) 2009-06-30
EA015676B1 true EA015676B1 (ru) 2011-10-31

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EA200870528A EA015676B1 (ru) 2006-05-11 2007-05-10 Композиции и способы ингибирования экспрессии гена pcsk9
EA201100907A EA020840B1 (ru) 2006-05-11 2007-05-14 Композиции и способы ингибирования экспрессии гена pcsk9

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US (10) US7605251B2 (enExample)
EP (8) EP2835429B1 (enExample)
JP (4) JP5570806B2 (enExample)
KR (2) KR101320916B1 (enExample)
CN (2) CN101484588B (enExample)
AU (2) AU2007249329C1 (enExample)
CA (2) CA2915441A1 (enExample)
EA (2) EA015676B1 (enExample)
ES (2) ES2874149T3 (enExample)
IL (3) IL195181A (enExample)
NZ (2) NZ587616A (enExample)
PL (2) PL2194128T3 (enExample)
SG (1) SG171676A1 (enExample)
WO (1) WO2007134161A2 (enExample)

Families Citing this family (174)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070173473A1 (en) * 2001-05-18 2007-07-26 Sirna Therapeutics, Inc. RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
KR101531400B1 (ko) * 2003-06-27 2015-06-26 암젠 프레몬트 인코포레이티드 상피 성장 인자 수용체의 결실 돌연변이체 지향 항체 및 그용도
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
EP2835429B1 (en) 2006-05-11 2017-12-13 Alnylam Pharmaceuticals Inc. Compositions and methods for inhibiting expression of the PCSK9 gene
EP2083861A4 (en) 2006-11-07 2010-11-24 Merck Sharp & Dohme ANTAGONISTS OF PCSK9
WO2008118212A2 (en) * 2006-11-08 2008-10-02 Veritas, Llc In vivo delivery of double stranded rna to a target cell
US8084437B2 (en) * 2006-11-27 2011-12-27 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US7910722B2 (en) 2007-07-05 2011-03-22 Florida State University Research Foundation RNAi therapeutic for treatment of hepatitis C infection
JOP20080381B1 (ar) 2007-08-23 2023-03-28 Amgen Inc بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9)
EP2245039A4 (en) * 2008-01-31 2012-06-06 Alnylam Pharmaceuticals Inc OPTIMIZED METHODS FOR EXPORING DSRNA TO TARGET THE PCSK9 GEN
AR070316A1 (es) 2008-02-07 2010-03-31 Merck & Co Inc Antagonistas de pcsk9 (proproteina subtilisina-kexina tipo 9)
AR070315A1 (es) 2008-02-07 2010-03-31 Merck & Co Inc Anticuerpos 1b20 antagonistas de pcsk9
AU2009213147A1 (en) 2008-02-11 2009-08-20 Rxi Pharmaceuticals Corp. Modified RNAi polynucleotides and uses thereof
AU2009227549A1 (en) * 2008-03-20 2009-09-24 Quark Pharmaceuticals, Inc. Novel siRNA compounds for inhibiting RTP801
JP2012502991A (ja) 2008-09-22 2012-02-02 アールエックスアイ ファーマシューティカルズ コーポレーション 皮膚適用におけるrna干渉
CA2739464C (en) 2008-10-03 2020-03-31 Opko Curna, Llc Treatment of apolipoprotein-a1 related diseases by inhibition of natural antisense transcript to apolipoprotein-a1
EP2370581B1 (en) 2008-12-04 2016-08-03 CuRNA, Inc. Treatment of vascular endothelial growth factor (vegf) related diseases by inhibition of natural antisense transcript to vegf
KR101829469B1 (ko) 2008-12-04 2018-03-30 큐알엔에이, 인크. Epo에 대한 천연 안티센스 전사체의 억제에 의해 에리트로포에틴(epo) 관련된 질환의 치료
WO2010065787A2 (en) 2008-12-04 2010-06-10 Curna, Inc. Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene
JO3672B1 (ar) 2008-12-15 2020-08-27 Regeneron Pharma أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9).
US9493774B2 (en) 2009-01-05 2016-11-15 Rxi Pharmaceuticals Corporation Inhibition of PCSK9 through RNAi
WO2010090762A1 (en) 2009-02-04 2010-08-12 Rxi Pharmaceuticals Corporation Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
WO2010093904A2 (en) 2009-02-12 2010-08-19 Curna, Inc. Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf
EP2408919B1 (en) 2009-03-16 2017-10-18 CuRNA, Inc. Treatment of nuclear factor (erythroid-derived 2)-like 2 (nrf2) related diseases by inhibition of natural antisense transcript to nrf2
EP2408920B1 (en) 2009-03-17 2017-03-08 CuRNA, Inc. Treatment of delta-like 1 homolog (dlk1) related diseases by inhibition of natural antisense transcript to dlk1
CN102803492B (zh) 2009-05-06 2016-06-29 库尔纳公司 通过抑制针对三重四脯氨酸(ttp)的天然反义转录物来治疗ttp相关疾病
KR101835889B1 (ko) 2009-05-06 2018-03-08 큐알엔에이, 인크. 지질 수송 및 대사 유전자에 대한 천연 안티센스 전사체의 억제에 의해 지질 수송 및 대사 유전자 관련된 질환의 치료
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
CN102575251B (zh) 2009-05-18 2018-12-04 库尔纳公司 通过抑制针对重编程因子的天然反义转录物来治疗重编程因子相关的疾病
US8895527B2 (en) 2009-05-22 2014-11-25 Curna, Inc. Treatment of transcription factor E3 (TFE3) and insulin receptor substrate 2(IRS2) related diseases by inhibition of natural antisense transcript to TFE3
CA2764683A1 (en) 2009-05-28 2010-12-02 Joseph Collard Treatment of antiviral gene related diseases by inhibition of natural antisense transcript to an antiviral gene
ES2804764T3 (es) 2009-06-01 2021-02-09 Halo Bio Rnai Therapeutics Inc Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos
NZ597504A (en) * 2009-06-15 2013-10-25 Alnylam Pharmaceuticals Inc Lipid formulated dsrna targeting the pcsk9 gene
US9051567B2 (en) 2009-06-15 2015-06-09 Tekmira Pharmaceuticals Corporation Methods for increasing efficacy of lipid formulated siRNA
WO2010148065A2 (en) 2009-06-16 2010-12-23 Curna, Inc. Treatment of paraoxonase 1 (pon1) related diseases by inhibition of natural antisense transcript to pon1
JP5944311B2 (ja) 2009-06-16 2016-07-05 クルナ・インコーポレーテッド コラーゲン遺伝子に対する天然アンチセンス転写物の抑制によるコラーゲン遺伝子関連疾患の治療
WO2010151671A2 (en) 2009-06-24 2010-12-29 Curna, Inc. Treatment of tumor necrosis factor receptor 2 (tnfr2) related diseases by inhibition of natural antisense transcript to tnfr2
KR101807324B1 (ko) 2009-06-26 2017-12-08 큐알엔에이, 인크. 다운 증후군 유전자에 대한 천연 안티센스 전사체의 억제에 의한 다운 증후군 유전자 관련된 질환의 치료
CA2767127A1 (en) 2009-07-01 2011-01-06 Protiva Biotherapeutics, Inc. Novel lipid formulations for delivery of therapeutic agents to solid tumors
EP2456870A1 (en) 2009-07-21 2012-05-30 Santaris Pharma A/S Antisense oligomers targeting pcsk9
KR101801407B1 (ko) 2009-07-24 2017-11-24 큐알엔에이, 인크. 시르투인 (sirt)에 대한 천연 안티센스 전사체의 억제에 의한 시르투인 관련된 질환의 치료
KR101802536B1 (ko) 2009-08-05 2017-11-28 큐알엔에이, 인크. 인슐린 유전자 (ins)에 대한 자연 안티센스 전사체의 저해에 의한 인슐린 유전자 (ins) 관련된 질환의 치료
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)
WO2011022606A2 (en) 2009-08-21 2011-02-24 Curna, Inc. Treatment of 'c terminus of hsp70-interacting protein' (chip) related diseases by inhibition of natural antisense transcript to chip
WO2011031482A2 (en) 2009-08-25 2011-03-17 Curna, Inc. Treatment of 'iq motif containing gtpase activating protein' (iqgap) related diseases by inhibition of natural antisense transcript to iqgap
WO2011028938A1 (en) * 2009-09-02 2011-03-10 Alnylam Pharmaceuticals, Inc. Methods for lowering serum cholestrol in a subject using inhibition of pcsk9
WO2011038031A1 (en) * 2009-09-22 2011-03-31 Alnylam Pharmaceuticals, Inc. Dual targeting sirna agents
WO2011038210A2 (en) 2009-09-25 2011-03-31 Curna, Inc. Treatment of filaggrin (flg) related diseases by modulation of flg expression and activity
DK3252068T3 (da) 2009-10-12 2025-08-25 Larry J Smith Metoder og sammensætninger til modulering af genekspression ved anvendelse af oligonukleotidbaserede lægemidler administreret in vivo eller in vitro
AR079336A1 (es) * 2009-12-11 2012-01-18 Irm Llc Antagonistas de la pro-proteina convertasa-subtilisina/quexina tipo 9 (pcsk9)
CA2782366A1 (en) 2009-12-16 2011-07-14 Opko Curna, Llc Treatment of membrane bound transcription factor peptidase, site 1 (mbtps1) related diseases by inhibition of natural antisense transcript to mbtps1
US20110152343A1 (en) * 2009-12-22 2011-06-23 Functional Genetics, Inc. Protease inhibitors and broad-spectrum antiviral
KR101891352B1 (ko) 2009-12-23 2018-08-24 큐알엔에이, 인크. 간세포 성장 인자(hgf)에 대한 천연 안티센스 전사체의 억제에 의한 hgf 관련 질환의 치료
US9068183B2 (en) 2009-12-23 2015-06-30 Curna, Inc. Treatment of uncoupling protein 2 (UCP2) related diseases by inhibition of natural antisense transcript to UCP2
CA2785173A1 (en) 2009-12-29 2011-07-28 Curna, Inc. Treatment of nuclear respiratory factor 1 (nrf1) related diseases by inhibition of natural antisense transcript to nrf1
WO2011090741A2 (en) 2009-12-29 2011-07-28 Opko Curna, Llc TREATMENT OF TUMOR PROTEIN 63 (p63) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPT TO p63
RU2016115782A (ru) 2009-12-31 2018-11-28 Курна, Инк. Лечение заболеваний, связанных с субстратом рецептора инсулина 2 (irs2), путем ингибирования природного антисмыслового транскрипта к irs2 и транскрипционному фактору е3 (tfe3)
CN102906264B (zh) 2010-01-04 2017-08-04 库尔纳公司 通过抑制干扰素调节因子8(irf8)的天然反义转录物而治疗irf8相关疾病
RU2612161C2 (ru) 2010-01-06 2017-03-02 Курна, Инк. Лечение заболеваний, связанных с геном развития поджелудочной железы, путем ингибирования природного антисмыслового транскрипта к гену развития поджелудочной железы
ES2664866T3 (es) 2010-01-11 2018-04-23 Curna, Inc. Tratamiento de enfermedades relacionadas con la globulina fijadora de hormonas sexuales (shbg) mediante inhibición del transcrito antisentido natural a shbg
KR101853510B1 (ko) 2010-01-25 2018-06-20 큐알엔에이, 인크. Rnase h1에 대한 천연 안티센스 전사체의 억제에 의한 rnase h1과 관련된 질환의 치료
US8962586B2 (en) 2010-02-22 2015-02-24 Curna, Inc. Treatment of pyrroline-5-carboxylate reductase 1 (PYCR1) related diseases by inhibition of natural antisense transcript to PYCR1
RU2612884C2 (ru) 2010-04-02 2017-03-13 Курна, Инк. Лечение заболеваний, связанных с колониестимулирующим фактором 3 (csf3), путем ингибирования природного антисмыслового транскрипта k csf3
EP3517613A1 (en) 2010-04-09 2019-07-31 CuRNA, Inc. Treatment of fibroblast growth factor 21 (fgf21) related diseases by inhibition of natural antisense transcript to fgf21
WO2011139387A1 (en) 2010-05-03 2011-11-10 Opko Curna, Llc Treatment of sirtuin (sirt) related diseases by inhibition of natural antisense transcript to a sirtuin (sirt)
TWI586356B (zh) 2010-05-14 2017-06-11 可娜公司 藉由抑制par4天然反股轉錄本治療par4相關疾病
EP2576783B1 (en) 2010-05-26 2017-11-29 CuRNA, Inc. Treatment of atonal homolog 1 (atoh1) related diseases by inhibition of natural antisense transcript to atoh1
CA2799596C (en) 2010-05-26 2020-09-22 Curna, Inc. Treatment of methionine sulfoxide reductase a (msra) related diseases by inhibition of natural antisense transcript to msra
PL2585596T3 (pl) 2010-06-23 2021-06-28 Curna, Inc. Leczenie chorób związanych z podjednostką alfa kanału sodowego bramkowanego napięciem (SCNA) poprzez hamowanie naturalnego transkryptu antysensownego SCNA
JP5998131B2 (ja) 2010-07-14 2016-09-28 カッパーアールエヌエー,インコーポレイテッド Discslargehomolog(dlg)dlg1への天然アンチセンス転写物の阻害によるdlg関連疾患の治療
WO2012047956A2 (en) 2010-10-06 2012-04-12 Opko Curna Llc Treatment of sialidase 4 (neu4) related diseases by inhibition of natural antisense transcript to neu4
WO2012054723A2 (en) 2010-10-22 2012-04-26 Opko Curna Llc Treatment of alpha-l-iduronidase (idua) related diseases by inhibition of natural antisense transcript to idua
EP2633046A4 (en) * 2010-10-29 2015-05-06 Alnylam Pharmaceuticals Inc COMPOSITIONS AND METHODS FOR INHIBITING PCSK9 GENES
US10000752B2 (en) 2010-11-18 2018-06-19 Curna, Inc. Antagonat compositions and methods of use
KR102010598B1 (ko) 2010-11-23 2019-08-13 큐알엔에이, 인크. Nanog에 대한 자연 안티센스 전사체의 저해에 의한 nanog 관련된 질환의 치료
AR084938A1 (es) 2011-01-28 2013-07-10 Sanofi Sa Anticuerpos humanos contra la proproteina convertasa subtilisina/kexina tipo 9 (anti pcsk9) para usar en metodos para tratar grupos de pacientes
EP2699271A4 (en) 2011-04-20 2015-10-07 Larry J Smith METHODS AND COMPOSITIONS FOR MODULATING GENE EXPRESSION USING COMPONENTS THAT SELF-ASSEMBLED IN CELLS AND PRODUCE RNAI ACTIVITY
WO2012170771A1 (en) 2011-06-09 2012-12-13 Curna, Inc. Treatment of frataxin (fxn) related diseases by inhibition of natural antisense transcript to fxn
AR087305A1 (es) 2011-07-28 2014-03-12 Regeneron Pharma Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit
WO2013036403A1 (en) 2011-09-06 2013-03-14 Curna, Inc. TREATMENT OF DISEASES RELATED TO ALPHA SUBUNITS OF SODIUM CHANNELS, VOLTAGE-GATED (SCNxA) WITH SMALL MOLECULES
SI2570135T1 (sl) * 2011-09-13 2016-05-31 Affiris Ag PCSK9 cepivo
AU2013222179B2 (en) 2012-02-24 2017-08-24 Arbutus Biopharma Corporat ion Trialkyl cationic lipids and methods of use thereof
DK2825648T3 (en) 2012-03-15 2018-10-15 Curna Inc TREATMENT OF BRAIN-DERIVATIVE NEUROTROPHIC FACTOR (BDNF) -related DISEASES BY INHIBITATION OF NATURAL ANTISENCE TRANSCRIPTION TO BDNF
US9255154B2 (en) 2012-05-08 2016-02-09 Alderbio Holdings, Llc Anti-PCSK9 antibodies and use thereof
PT2929031T (pt) 2012-12-05 2018-01-19 Alnylam Pharmaceuticals Inc Composições de irna de pcsk9 e métodos de seu uso
WO2014093709A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof
IL239317B (en) 2012-12-12 2022-07-01 Broad Inst Inc Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
EP2931899A1 (en) 2012-12-12 2015-10-21 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof
TW201515650A (zh) 2013-05-06 2015-05-01 艾爾妮蘭製藥公司 遞送經脂質調配之核酸分子之劑量及方法
EP2810955A1 (en) 2013-06-07 2014-12-10 Sanofi Methods for inhibiting atherosclerosis by administering an inhibitor of PCSK9
EP2862877A1 (en) 2013-10-18 2015-04-22 Sanofi Methods for inhibiting atherosclerosis by administering an inhibitor of PCSK9
TW201534324A (zh) 2013-06-07 2015-09-16 Sanofi Sa 藉由投與pcsk9抑制劑抑制動脈粥狀硬化的方法
CN106062197A (zh) 2013-06-17 2016-10-26 布罗德研究所有限公司 用于序列操纵的串联指导系统、方法和组合物的递送、工程化和优化
CN105793425B (zh) 2013-06-17 2021-10-26 布罗德研究所有限公司 使用病毒组分靶向障碍和疾病的crispr-cas系统和组合物的递送、用途和治疗应用
WO2014204725A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation
EP3620524A1 (en) * 2013-06-17 2020-03-11 The Broad Institute, Inc. Delivery, engineering and optimization of systems, methods and compositions for targeting and modeling diseases and disorders of post mitotic cells
AU2014281028B2 (en) 2013-06-17 2020-09-10 Massachusetts Institute Of Technology Delivery and use of the CRISPR-Cas systems, vectors and compositions for hepatic targeting and therapy
EP3011033B1 (en) 2013-06-17 2020-02-19 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof
SG10201908122XA (en) 2013-06-27 2019-10-30 Roche Innovation Ct Copenhagen As Antisense oligomers and conjugates targeting pcsk9
CN118813621A (zh) 2013-12-12 2024-10-22 布罗德研究所有限公司 用于基因组编辑的crispr-cas系统和组合物的递送、用途和治疗应用
MX374530B (es) 2013-12-12 2025-03-06 Broad Inst Inc Suministro, uso y aplicaciones terapeuticas de los sistemas y composiciones crispr-cas para actuar sobre hbv y trastornos y enfermedades virales.
EP3080259B1 (en) 2013-12-12 2023-02-01 The Broad Institute, Inc. Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation
WO2015089364A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Crystal structure of a crispr-cas system, and uses thereof
EP3080257A1 (en) 2013-12-12 2016-10-19 The Broad Institute Inc. Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders
WO2015089486A2 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems
US8992927B1 (en) 2014-07-15 2015-03-31 Kymab Limited Targeting human NAV1.7 variants for treatment of pain
US9067998B1 (en) 2014-07-15 2015-06-30 Kymab Limited Targeting PD-1 variants for treatment of cancer
US9914769B2 (en) 2014-07-15 2018-03-13 Kymab Limited Precision medicine for cholesterol treatment
US8980273B1 (en) 2014-07-15 2015-03-17 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
US8945560B1 (en) 2014-07-15 2015-02-03 Kymab Limited Method of treating rheumatoid arthritis using antibody to IL6R
US9045548B1 (en) 2014-07-15 2015-06-02 Kymab Limited Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment
US9034332B1 (en) 2014-07-15 2015-05-19 Kymab Limited Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment
US9023359B1 (en) 2014-07-15 2015-05-05 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
US9017678B1 (en) 2014-07-15 2015-04-28 Kymab Limited Method of treating rheumatoid arthritis using antibody to IL6R
US9045545B1 (en) 2014-07-15 2015-06-02 Kymab Limited Precision medicine by targeting PD-L1 variants for treatment of cancer
US8986691B1 (en) 2014-07-15 2015-03-24 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
US8883157B1 (en) 2013-12-17 2014-11-11 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
US8986694B1 (en) 2014-07-15 2015-03-24 Kymab Limited Targeting human nav1.7 variants for treatment of pain
US9051378B1 (en) 2014-07-15 2015-06-09 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
RU2697094C2 (ru) * 2013-12-27 2019-08-12 Бонак Корпорейшн ИСКУССТВЕННАЯ мкРНК С СООТВЕТСТВИЕМ ДЛЯ КОНТРОЛЯ ЭКСПРЕССИИ ГЕНОВ И ЕЕ ПРИМЕНЕНИЕ
GB201403775D0 (en) 2014-03-04 2014-04-16 Kymab Ltd Antibodies, uses & methods
US9139648B1 (en) 2014-07-15 2015-09-22 Kymab Limited Precision medicine by targeting human NAV1.9 variants for treatment of pain
US9150660B1 (en) 2014-07-15 2015-10-06 Kymab Limited Precision Medicine by targeting human NAV1.8 variants for treatment of pain
KR20240017117A (ko) 2014-07-16 2024-02-06 사노피 바이오테크놀로지 이형접합성 가족성 고콜레스테롤혈증(heFH) 환자의 치료방법
JOP20200115A1 (ar) * 2014-10-10 2017-06-16 Alnylam Pharmaceuticals Inc تركيبات وطرق لتثبيط التعبير الجيني عن hao1 (حمض أوكسيداز هيدروكسيلي 1 (أوكسيداز جليكولات))
EP3889260A1 (en) 2014-12-12 2021-10-06 The Broad Institute, Inc. Protected guide rnas (pgrnas)
AU2015369725A1 (en) 2014-12-24 2017-06-29 Massachusetts Institute Of Technology CRISPR having or associated with destabilization domains
ES2789049T3 (es) * 2014-12-26 2020-10-23 Nitto Denko Corp Agentes de interferencia de ARN para modulación génica de GST-pi
US20180002702A1 (en) 2014-12-26 2018-01-04 Nitto Denko Corporation Methods and compositions for treating malignant tumors associated with kras mutation
US10264976B2 (en) 2014-12-26 2019-04-23 The University Of Akron Biocompatible flavonoid compounds for organelle and cell imaging
US10792299B2 (en) 2014-12-26 2020-10-06 Nitto Denko Corporation Methods and compositions for treating malignant tumors associated with kras mutation
US11045488B2 (en) 2014-12-26 2021-06-29 Nitto Denko Corporation RNA interference agents for GST-π gene modulation
WO2016205759A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Engineering and optimization of systems, methods, enzymes and guide scaffolds of cas9 orthologs and variants for sequence manipulation
WO2016205613A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Crispr enzyme mutations reducing off-target effects
EA201890519A1 (ru) 2015-08-18 2018-07-31 Ридженерон Фармасьютикалз, Инк. Ингибирующие антитела против pcsk9 для лечения пациентов с гиперлипидемией, подвергающихся аферезу липопротеинов
WO2017035278A1 (en) 2015-08-24 2017-03-02 Halo-Bio Rnai Therapeutics, Inc. Polynucleotide nanoparticles for the modulation of gene expression and uses thereof
KR102793532B1 (ko) 2015-08-25 2025-04-14 알닐람 파마슈티칼스 인코포레이티드 전구단백질 컨버타제 서브틸리신 켁신 (pcsk9) 유전자-관련 장애를 치료하기 위한 방법 및 조성물
US11021707B2 (en) 2015-10-19 2021-06-01 Phio Pharmaceuticals Corp. Reduced size self-delivering nucleic acid compounds targeting long non-coding RNA
CN116903741A (zh) 2016-06-20 2023-10-20 科马布有限公司 特异性结合于pd-l1的抗体或其抗原结合片段及其用途
EP3529360B1 (en) * 2016-10-18 2024-04-17 Novartis AG Methods for preventing cardiovascular events through proprotein convertase subtilisin kexin 9 (pcsk9) protein reduction
WO2018083248A1 (en) 2016-11-03 2018-05-11 Kymab Limited Antibodies, combinations comprising antibodies, biomarkers, uses & methods
JOP20190112A1 (ar) 2016-11-14 2019-05-14 Amgen Inc علاجات مدمجة لتصلب الشرايين، شاملة مرض قلبي وعائي تصلبي
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
CN108265052B (zh) * 2016-12-30 2021-05-28 苏州瑞博生物技术股份有限公司 一种小干扰核酸和药物组合物及其用途
JP2019508379A (ja) * 2017-02-16 2019-03-28 日東電工株式会社 悪性腫瘍に対する治療方法及び治療用組成物
JOP20190215A1 (ar) * 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc مُعدّلات التعبير الوراثي عن pcsk9
US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
US11414661B2 (en) 2017-12-01 2022-08-16 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate containing nucleic acid, preparation method therefor and use thereof
JP7273417B2 (ja) 2017-12-01 2023-05-15 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、当該核酸を含む組成物および複合体ならびに調製方法と使用
JP7727308B2 (ja) 2017-12-01 2025-08-21 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 二本鎖オリゴヌクレオチド、二本鎖オリゴヌクレオチドを含む組成物および複合体ならびに調製方法と使用
US12083142B2 (en) 2017-12-01 2024-09-10 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate comprising the same, and preparation method and use thereof
JP7365052B2 (ja) 2017-12-01 2023-10-19 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、当該核酸を含む組成物及び複合体ならびに調製方法と使用
CN109957567B (zh) * 2017-12-26 2022-09-23 阿格纳生物制药有限公司 一种抑制PCSK9基因表达的siRNA分子及其应用
CN109957565B (zh) * 2017-12-26 2023-04-07 广州市锐博生物科技有限公司 一种修饰的siRNA分子及其应用
AU2017445584B2 (en) * 2017-12-26 2021-08-12 Argorna Pharmaceuticals Limited SiRNA molecule inhibiting the expression of the PCSK9 gene and use thereof
DK3732185T3 (da) 2017-12-29 2025-03-31 Suzhou Ribo Life Science Co Ltd Konjugater og fremstilling og anvendelse heraf
KR102749200B1 (ko) * 2018-04-18 2025-01-03 다이서나 파마수이티컬, 인크. 고콜레스테롤혈증 및 관련 상태를 치료하기 위한 pcsk9 표적화 올리고뉴클레오티드
US11918600B2 (en) 2018-08-21 2024-03-05 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition and conjugate containing nucleic acid, and use thereof
CN111655297A (zh) 2018-09-30 2020-09-11 苏州瑞博生物技术有限公司 一种siRNA缀合物及其制备方法和用途
CN111378656B (zh) * 2018-12-28 2022-07-26 苏州瑞博生物技术股份有限公司 一种抑制埃博拉病毒的核酸、含有该核酸的药物组合物及其用途
EP3903830A4 (en) 2018-12-28 2023-04-26 Suzhou Ribo Life Science Co., Ltd. NUCLEIC ACID, COMPOSITION AND CONJUGATE WITH NUCLEIC ACID, PROCESS FOR THEIR PREPARATION AND ITS USE
AU2020280438B2 (en) 2019-05-22 2025-03-06 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use
CN114173762A (zh) * 2019-06-04 2022-03-11 塔夫茨大学信托人 用于mRNA递送的合成脂质
WO2021037972A1 (en) * 2019-08-27 2021-03-04 Sanofi Compositions and methods for inhibiting pcsk9
US12378560B2 (en) 2019-10-29 2025-08-05 Northwestern University Sequence multiplicity within spherical nucleic acids
US20230183694A1 (en) * 2020-03-16 2023-06-15 Argonaute RNA Limited Antagonist of pcsk9
WO2022089486A1 (zh) * 2020-10-28 2022-05-05 江苏柯菲平医药股份有限公司 抑制PCSK9基因表达的siRNA及其修饰物与应用
WO2023017004A1 (en) * 2021-08-09 2023-02-16 Cargene Therapeutics Pte. Ltd. Inhibitory nucleic acids for pcsk9
CN113980966B (zh) * 2021-09-29 2024-09-20 阿格纳生物制药有限公司 一种抑制pcsk9靶基因表达的核酸序列及其应用
WO2024222898A1 (zh) * 2023-04-28 2024-10-31 北京福元医药股份有限公司 用于抑制marc1基因表达的双链核糖核酸及其修饰物、缀合物和用途
WO2025006782A2 (en) * 2023-06-30 2025-01-02 Chroma Medicine, Inc. Guide rna compositions
CN118147134B (zh) * 2023-11-06 2025-02-25 北京悦康科创医药科技股份有限公司 靶向调控PCSK9基因表达的siRNA及其应用
CN117384907B (zh) * 2023-12-11 2024-03-29 上海鼎新基因科技有限公司 抑制PCSK9表达的siRNA分子及其应用

Family Cites Families (133)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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
US5166315A (en) 1989-12-20 1992-11-24 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
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
ATE68013T1 (de) 1985-07-05 1991-10-15 Whitehead Biomedical Inst Expression von fremdem genetischem material in epithelzellen.
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
US5139941A (en) 1985-10-31 1992-08-18 University Of Florida Research Foundation, Inc. AAV transduction vectors
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
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
WO1989002468A1 (en) 1987-09-11 1989-03-23 Whitehead Institute For Biomedical Research Transduced fibroblasts and uses therefor
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
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
WO1989005345A1 (en) 1987-12-11 1989-06-15 Whitehead Institute For Biomedical Research Genetic modification of endothelial cells
ATE152169T1 (de) 1988-02-05 1997-05-15 Whitehead Biomedical Inst Modifizierte hepatozyten und deren anwendung
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
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
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
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5223168A (en) 1989-12-12 1993-06-29 Gary Holt Surface cleaner and treatment
US5457191A (en) 1990-01-11 1995-10-10 Isis Pharmaceuticals, Inc. 3-deazapurines
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5506351A (en) 1992-07-23 1996-04-09 Isis Pharmaceuticals Process for the preparation of 2'-O-alkyl guanosine and related compounds
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5212295A (en) 1990-01-11 1993-05-18 Isis Pharmaceuticals Monomers for preparation of oligonucleotides having chiral phosphorus linkages
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
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
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
IL113519A (en) 1990-08-03 1997-11-20 Sterling Winthrop Inc Oligonucleoside sequences of from about 6 to about 200 bases having a three atom internucleoside linkage, their preparation and pharmaceutical compositions for inhibiting gene expression containing said oligonucleosides
US6262241B1 (en) 1990-08-13 2001-07-17 Isis Pharmaceuticals, Inc. Compound for detecting and modulating RNA activity and gene expression
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
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
AU656544B2 (en) 1990-10-31 1995-02-09 Brigham And Women's Hospital Genetic modification of endothelial cells
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
EP0621944B1 (en) 1991-07-25 1997-03-05 The Whitaker Corporation Liquid level sensor
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
US5599797A (en) 1991-10-15 1997-02-04 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
JP2823959B2 (ja) 1991-10-24 1998-11-11 アイシス・ファーマシューティカルス・インコーポレーテッド 改良された取り込みおよびその他の性質を持つ誘導化オリゴヌクレオチド
US5252479A (en) 1991-11-08 1993-10-12 Research Corporation Technologies, Inc. Safe vector for gene therapy
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
US5587308A (en) 1992-06-02 1996-12-24 The United States Of America As Represented By The Department Of Health & Human Services Modified adeno-associated virus vector capable of expression from a novel promoter
US5478745A (en) 1992-12-04 1995-12-26 University Of Pittsburgh Recombinant viral vector system
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
WO1994022891A1 (en) 1993-03-31 1994-10-13 Sterling Winthrop Inc. Oligonucleotides with amide linkages replacing phosphodiester linkages
US5571902A (en) 1993-07-29 1996-11-05 Isis Pharmaceuticals, Inc. Synthesis of oligonucleotides
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US6054299A (en) 1994-04-29 2000-04-25 Conrad; Charles A. Stem-loop cloning vector and method
US5554746A (en) 1994-05-16 1996-09-10 Isis Pharmaceuticals, Inc. Lactam nucleic acids
AU723163B2 (en) 1995-06-07 2000-08-17 Tekmira Pharmaceuticals Corporation Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
US6506559B1 (en) 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
SI1068311T1 (sl) 1998-04-08 2011-07-29 Commw Scient Ind Res Org Postopki in sredstva za pridobivanje modificiranih fenotipov
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
IL142490A0 (en) 1998-10-09 2002-03-10 Ingene Inc ENZYMATIC SYNTHESIS OF ssDNA
BR9914773A (pt) 1998-10-09 2002-02-05 Ingene Inc Conjunto de elementos genéricos, método para a produção de dna de cordão único, transcrição de mrna, construção de ácido nucléico, transcrição de ssdna, vetor, sistema vetor, célula hospedeira, conjunto para a produção de uma sequência de ácido nucléico de cordão único, método para a produção in vivo ou in vitro de uma sequência de ácido nucléico de cordão único, transcrição de cdna de cordão único, ácido nucléico inibidor, molécula heteroduplex, e composição farmacêutica
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
US6271359B1 (en) 1999-04-14 2001-08-07 Musc Foundation For Research Development Tissue-specific and pathogen-specific toxic agents and ribozymes
DE10100586C1 (de) 2001-01-09 2002-04-11 Ribopharma Ag Verfahren zur Hemmung der Expression eines Ziegens
US20030229037A1 (en) 2000-02-07 2003-12-11 Ulrich Massing Novel cationic amphiphiles
WO2003070918A2 (en) 2002-02-20 2003-08-28 Ribozyme Pharmaceuticals, Incorporated Rna interference by modified short interfering nucleic acid
US20070026394A1 (en) 2000-02-11 2007-02-01 Lawrence Blatt Modulation of gene expression associated with inflammation proliferation and neurite outgrowth using nucleic acid based technologies
EP1873259B1 (en) 2000-12-01 2012-01-25 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. RNA interference mediated by 21 and 22nt RNAs
US20080249040A1 (en) 2001-05-18 2008-10-09 Sirna Therapeutics, Inc. RNA interference mediated inhibition of sterol regulatory element binding protein 1 (SREBP1) gene expression using short interfering nucleic acid (siNA)
US20030170891A1 (en) 2001-06-06 2003-09-11 Mcswiggen James A. RNA interference mediated inhibition of epidermal growth factor receptor gene expression using short interfering nucleic acid (siNA)
US20070173473A1 (en) 2001-05-18 2007-07-26 Sirna Therapeutics, Inc. RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
US20040009216A1 (en) 2002-04-05 2004-01-15 Rodrigueza Wendi V. Compositions and methods for dosing liposomes of certain sizes to treat or prevent disease
US7956176B2 (en) 2002-09-05 2011-06-07 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
EP2314691A3 (en) 2002-11-14 2012-01-18 Dharmacon, Inc. Fuctional and hyperfunctional siRNA
DE10302421A1 (de) 2003-01-21 2004-07-29 Ribopharma Ag Doppelsträngige Ribonukleinsäure mit verbesserter Wirksamkeit
ATE479752T1 (de) 2003-03-07 2010-09-15 Alnylam Pharmaceuticals Inc Therapeutische zusammensetzungen
WO2004090108A2 (en) 2003-04-03 2004-10-21 Alnylam Pharmaceuticals Irna conjugates
EP1471152A1 (en) * 2003-04-25 2004-10-27 Institut National De La Sante Et De La Recherche Medicale (Inserm) Mutations in the human PCSK9 gene associated to hypercholesterolemia
EP3604537B1 (en) * 2003-06-13 2021-12-08 Alnylam Europe AG Double-stranded ribonucleic acid with increased effectiveness in an organism
JP4951338B2 (ja) 2003-07-16 2012-06-13 プロチバ バイオセラピューティクス インコーポレイティッド 脂質に封入された干渉rna
CA2543013A1 (en) * 2003-10-23 2005-05-19 Sirna Therapeutics, Inc. Rna interference mediated inhibition of nogo and nogo receptor gene expression using short interfering nucleic acid (sina)
EP1778298A4 (en) 2004-04-01 2010-03-31 Univ Pennsylvania LIPOPROTEIN-NANO PLATFORMS
AU2005252273B2 (en) 2004-06-07 2011-04-28 Arbutus Biopharma Corporation Lipid encapsulated interfering RNA
US7745651B2 (en) 2004-06-07 2010-06-29 Protiva Biotherapeutics, Inc. Cationic lipids and methods of use
WO2007086881A2 (en) 2005-02-14 2007-08-02 Sirna Therapeutics, Inc. Cationic lipids and formulated molecular compositions containing them
ATE541928T1 (de) 2005-03-31 2012-02-15 Calando Pharmaceuticals Inc Inhibitoren der untereinheit 2 der ribonukleotidreduktase und ihre verwendungen
US7915230B2 (en) 2005-05-17 2011-03-29 Molecular Transfer, Inc. Reagents for transfection of eukaryotic cells
EP1937213B1 (en) 2005-07-27 2017-10-25 Protiva Biotherapeutics Inc. Systems and methods for manufacturing liposomes
EP1948674A4 (en) 2005-11-02 2009-02-04 Protiva Biotherapeutics Inc MODIFIED SIRNA MOLECULES AND APPLICATIONS THEREOF
WO2007056861A1 (en) 2005-11-18 2007-05-24 Protiva Biotherapeutics, Inc. Sirna silencing of influenza virus gene expression
KR20150038522A (ko) 2006-03-31 2015-04-08 알닐람 파마슈티칼스 인코포레이티드 Eg5 유전자의 발현을 억제하는 이본쇄 리보핵산
EP2835429B1 (en) 2006-05-11 2017-12-13 Alnylam Pharmaceuticals Inc. Compositions and methods for inhibiting expression of the PCSK9 gene
US8598333B2 (en) 2006-05-26 2013-12-03 Alnylam Pharmaceuticals, Inc. SiRNA silencing of genes expressed in cancer
CA2658183A1 (en) * 2006-07-17 2008-01-24 Sirna Therapeutics Inc. Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina)
CN105030654A (zh) 2006-10-03 2015-11-11 阿尔尼拉姆医药品有限公司 含脂质的制品
US8084437B2 (en) 2006-11-27 2011-12-27 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
WO2008109369A2 (en) 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting tnf gene expression and uses thereof
JOP20080381B1 (ar) 2007-08-23 2023-03-28 Amgen Inc بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9)
AU2008342535B2 (en) 2007-12-27 2015-02-05 Arbutus Biopharma Corporation Silencing of polo-like kinase expression using interfering RNA
EP3100718B1 (en) 2008-01-02 2019-11-27 Arbutus Biopharma Corporation Improved compositions and methods for the delivery of nucleic acids
EP2245039A4 (en) 2008-01-31 2012-06-06 Alnylam Pharmaceuticals Inc OPTIMIZED METHODS FOR EXPORING DSRNA TO TARGET THE PCSK9 GEN
EA201301171A1 (ru) 2008-03-05 2014-10-30 Элнилэм Фармасьютикалз, Инк. Композиции и способы ингибирования экспрессии генов eg5 и vegf
WO2009114475A2 (en) 2008-03-09 2009-09-17 Intradigm Corporation Compositions comprising human pcsk9 and apolipoprotein b sirna and methods of use
JP5475753B2 (ja) 2008-04-15 2014-04-16 プロチバ バイオセラピューティクス インコーポレイティッド 核酸送達用の脂質製剤
JP5791505B2 (ja) 2008-10-20 2015-10-07 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Alnylam Pharmaceuticals, Inc. トランスチレチンの発現を阻害するための組成物および方法
MX338780B (es) 2008-11-10 2016-05-02 Alnylam Pharmaceuticals Inc Lipidos y composiciones novedosas para el suministro de terapeuticos.
WO2010068816A1 (en) 2008-12-10 2010-06-17 Alnylam Pharmaceuticals, Inc. Gnaq targeted dsrna compositions and methods for inhibiting expression
US8311190B2 (en) * 2008-12-23 2012-11-13 International Business Machines Corporation Performing human client verification over a voice interface
EP3243504A1 (en) 2009-01-29 2017-11-15 Arbutus Biopharma Corporation Improved lipid formulation
EP3097908A1 (en) 2009-05-05 2016-11-30 Arbutus Biopharma Corporation Lipid compositions
PL2440183T3 (pl) 2009-06-10 2019-01-31 Arbutus Biopharma Corporation Ulepszona formulacja lipidowa
NZ597504A (en) 2009-06-15 2013-10-25 Alnylam Pharmaceuticals Inc Lipid formulated dsrna targeting the pcsk9 gene
US9051567B2 (en) 2009-06-15 2015-06-09 Tekmira Pharmaceuticals Corporation Methods for increasing efficacy of lipid formulated siRNA
EP2456870A1 (en) 2009-07-21 2012-05-30 Santaris Pharma A/S Antisense oligomers targeting pcsk9

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DOWNWARD, J. Science, medicine, and the future RNA interference, BMJ, 2004, vol. 328, pages 1245-1248. *
GRAHAM et al. Antisense inhibition of proportein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. Journal of Lipid Research, 2007, vol. 48, pages 763-767. GENBANK ACCESSION NO: NM_174936. Homo sapiens proprotein convertase subtilisin/kexin type 9 (PCSK9), mRNA. Sept, 2007, see nucleotide sequence. BASAK, A. Inhibitors of proprotein convertases. Journal of Molecular Medicine, 2005, vol. 83, pages 844, 855, see particularly Table 1 and Table 2. ELBASHIR et al. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. The Embo Journal, 2001, vol. 20, pages 6877-6888, see entire article for siRNA design. *
LU et al. (2005) in RNA Interference Technology (Cambridge, Appasani, ed.). Delivering siRNA in vivo for functional genomics and novel therapeutics, pages 303-317. SAMARSKY et al. (2005) in RNA Interference Technology (Cambridge, Appasani, ed.). RNAi in drug development: Practical considerations, pages 384-395. *

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