ES2543004T3 - Composiciones y métodos para inhibir la expresión de transtiretina - Google Patents

Composiciones y métodos para inhibir la expresión de transtiretina Download PDF

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Publication number
ES2543004T3
ES2543004T3 ES09810834.3T ES09810834T ES2543004T3 ES 2543004 T3 ES2543004 T3 ES 2543004T3 ES 09810834 T ES09810834 T ES 09810834T ES 2543004 T3 ES2543004 T3 ES 2543004T3
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Prior art keywords
ttr
seq
strand
rnads
sequence
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English (en)
Spanish (es)
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Dinah Wen-Yee Sah
Gregory Hinkle
Rene Alvarez
Stuart Milstein
Qingmin Chen
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Alnylam Pharmaceuticals Inc
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Alnylam Pharmaceuticals Inc
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    • 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
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    • C07F9/02—Phosphorus compounds
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ES09810834.3T 2008-10-20 2009-10-20 Composiciones y métodos para inhibir la expresión de transtiretina Active ES2543004T3 (es)

Applications Claiming Priority (13)

Application Number Priority Date Filing Date Title
US10695608P 2008-10-20 2008-10-20
US106956P 2008-10-20
US11573808P 2008-11-18 2008-11-18
US115738P 2008-11-18
US15667009P 2009-03-02 2009-03-02
US156670P 2009-03-02
US18554509P 2009-06-09 2009-06-09
US185545P 2009-06-09
US24278309P 2009-09-15 2009-09-15
US242783P 2009-09-15
US24479409P 2009-09-22 2009-09-22
US244794P 2009-09-22
PCT/US2009/061381 WO2010048228A2 (en) 2008-10-20 2009-10-20 Compositions and methods for inhibiting expression of transthyretin

Publications (1)

Publication Number Publication Date
ES2543004T3 true ES2543004T3 (es) 2015-08-13

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ID=42062316

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Application Number Title Priority Date Filing Date
ES09810834.3T Active ES2543004T3 (es) 2008-10-20 2009-10-20 Composiciones y métodos para inhibir la expresión de transtiretina
ES15151452.8T Active ES2656516T3 (es) 2008-10-20 2009-10-20 Composiciones y métodos para inhibir la expresión de transtiretina

Family Applications After (1)

Application Number Title Priority Date Filing Date
ES15151452.8T Active ES2656516T3 (es) 2008-10-20 2009-10-20 Composiciones y métodos para inhibir la expresión de transtiretina

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US (9) US8168775B2 (enExample)
EP (4) EP2344639B1 (enExample)
JP (7) JP5791505B2 (enExample)
KR (6) KR102031027B1 (enExample)
CN (3) CN102186978B (enExample)
AU (1) AU2009307677C1 (enExample)
CA (3) CA2739895C (enExample)
CY (3) CY1116944T1 (enExample)
DK (2) DK2937418T3 (enExample)
EA (3) EA029762B1 (enExample)
ES (2) ES2543004T3 (enExample)
HR (2) HRP20150796T1 (enExample)
HU (3) HUE037875T2 (enExample)
IL (5) IL302142B2 (enExample)
LT (2) LT2937418T (enExample)
LU (1) LUC00098I2 (enExample)
MX (4) MX360460B (enExample)
NL (1) NL300965I2 (enExample)
NO (2) NO2937418T3 (enExample)
NZ (2) NZ602404A (enExample)
PL (2) PL2344639T3 (enExample)
PT (2) PT2937418T (enExample)
SG (3) SG10201703242XA (enExample)
SI (2) SI2937418T1 (enExample)
SM (2) SMT201800027T1 (enExample)
WO (1) WO2010048228A2 (enExample)
ZA (1) ZA201102876B (enExample)

Families Citing this family (135)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9228186B2 (en) * 2002-11-14 2016-01-05 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US20050244869A1 (en) * 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
ES2874149T3 (es) * 2006-05-11 2021-11-04 Alnylam Pharmaceuticals Inc Composiciones y métodos para inhibir la expresión del gen PCSK9
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
CA2739895C (en) 2008-10-20 2018-09-25 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin
CA2743139C (en) 2008-11-10 2019-04-02 Alnylam Pharmaceuticals, Inc. Novel lipids and compositions for the delivery of therapeutics
NZ593618A (en) * 2008-12-10 2013-02-22 Alnylam Pharmaceuticals Inc Gnaq targeted dsrna compositions and methods for inhibiting expression
EP3243504A1 (en) * 2009-01-29 2017-11-15 Arbutus Biopharma Corporation Improved lipid formulation
NZ622843A (en) * 2009-06-10 2015-10-30 Tekmira Pharmaceuticals Corp Improved lipid formulation
WO2010147992A1 (en) 2009-06-15 2010-12-23 Alnylam Pharmaceuticals, Inc. Methods for increasing efficacy of lipid formulated sirna
NZ597504A (en) * 2009-06-15 2013-10-25 Alnylam Pharmaceuticals Inc Lipid formulated dsrna targeting the pcsk9 gene
ES2613498T3 (es) 2009-07-01 2017-05-24 Protiva Biotherapeutics Inc. Nuevas formulaciones de lípidos para el suministro de agentes terapéuticos a tumores sólidos
US9029338B2 (en) * 2009-08-14 2015-05-12 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of a gene from the ebola virus
JP5723378B2 (ja) * 2009-11-03 2015-05-27 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． トランスサイレチン（ｔｔｒ）を阻害する脂質製剤化組成物及び方法
ES2893199T3 (es) * 2010-03-29 2022-02-08 Alnylam Pharmaceuticals Inc Terapia de ARNbc para amiloidosis ocular relacionada con transtiretina (TTR)
US20230340473A1 (en) * 2010-03-29 2023-10-26 Alnylam Pharmaceuticals, Inc. Sirna therapy for transthyretin (ttr) related ocular amyloidosis
RS56011B1 (sr) 2010-04-29 2017-09-29 Ionis Pharmaceuticals Inc Modulacija ekspresije transtiretina
EP2569276B1 (en) * 2010-05-12 2021-02-24 Arbutus Biopharma Corporation Novel cationic lipids and methods of use thereof
EP3456827A3 (en) * 2010-06-02 2019-05-08 Alnylam Pharmaceuticals, Inc. Compositions and methods directed to treating liver fibrosis
US9006417B2 (en) 2010-06-30 2015-04-14 Protiva Biotherapeutics, Inc. Non-liposomal systems for nucleic acid delivery
KR20130124308A (ko) 2010-10-21 2013-11-13 머크 샤프 앤드 돔 코포레이션 올리고뉴클레오티드 전달을 위한 신규 저분자량 양이온성 지질
WO2012068176A1 (en) 2010-11-15 2012-05-24 Life Technologies Corporation Amine-containing transfection reagents and methods for making and using same
US9127275B2 (en) * 2010-12-10 2015-09-08 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of klf-1 and bcl11a genes
EP2525223A1 (en) * 2011-05-19 2012-11-21 Universiteit Maastricht In vitro method for predicting in vivo genotoxicity of chemical compounds.
MX345095B (es) 2011-06-21 2017-01-17 Alnylam Pharmaceuticals Inc Composiciones de arni similares a angiopoyetina 3 (angptl3) y metodos para su uso.
US9228188B2 (en) * 2011-06-21 2016-01-05 Alnylam Pharmaceuticals, Inc. Compositions and method for inhibiting hepcidin antimicrobial peptide (HAMP) or HAMP-related 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
US9399775B2 (en) * 2011-11-18 2016-07-26 Alnylam Pharmaceuticals, Inc. RNAi agents, compositions and methods of use thereof for treating transthyretin (TTR) associated diseases
CA2856742A1 (en) 2011-12-07 2013-06-13 Alnylam Pharmaceuticals, Inc. Biodegradable lipids for the delivery of active agents
US9035039B2 (en) * 2011-12-22 2015-05-19 Protiva Biotherapeutics, Inc. Compositions and methods for silencing SMAD4
EP2922554B1 (en) * 2012-11-26 2022-02-23 ModernaTX, Inc. Terminally modified rna
PT2929031T (pt) 2012-12-05 2018-01-19 Alnylam Pharmaceuticals Inc Composições de irna de pcsk9 e métodos de seu uso
WO2014093701A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof
RU2721275C2 (ru) 2012-12-12 2020-05-18 Те Брод Инститьют, Инк. Доставка, конструирование и оптимизация систем, способов и композиций для манипуляции с последовательностями и применения в терапии
JP2016504050A (ja) 2013-01-17 2016-02-12 モデルナ セラピューティクス インコーポレイテッドＭｏｄｅｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． 細胞表現型の改変のためのシグナルセンサーポリヌクレオチド
JP2016514091A (ja) 2013-02-08 2016-05-19 ミスフォールディング ダイアグノスティクス， インコーポレイテッド トランスサイレチン抗体およびその使用
WO2014165825A2 (en) 2013-04-04 2014-10-09 President And Fellows Of Harvard College Therapeutic uses of genome editing with crispr/cas systems
IL296543B2 (en) * 2013-05-01 2025-02-01 Ionis Pharmaceuticals Inc Compositions and methods for modulating HBV and TTR expression
EP3725885A1 (en) 2013-06-17 2020-10-21 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof
BR112015031608A2 (pt) 2013-06-17 2017-08-22 Massachusetts Inst Technology Aplicação e uso dos sistemas crispr-cas, vetores e composições para direcionamento e terapia hepáticos
EP3019595A4 (en) * 2013-07-09 2016-11-30 THERAPEUTIC USES OF A GENERIC CHANGE WITH CRISPR / CAS SYSTEMS
WO2015042564A1 (en) * 2013-09-23 2015-03-26 Alnylam Pharmaceuticals, Inc. Methods for treating or preventing transthyretin (ttr) associated diseases
CA2925107A1 (en) * 2013-10-02 2015-04-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the lect2 gene
AU2014360314B2 (en) * 2013-12-06 2018-04-26 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of transthyretin (TTR) by double-stranded RNA
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
EP3080261B1 (en) 2013-12-12 2019-05-22 The Broad Institute, Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for hbv and viral diseases and disorders
EP4219699A1 (en) 2013-12-12 2023-08-02 The Broad Institute, Inc. Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation
US9856475B2 (en) 2014-03-25 2018-01-02 Arcturus Therapeutics, Inc. Formulations for treating amyloidosis
JP6771387B2 (ja) 2014-03-25 2020-10-21 アークトゥラス・セラピューティクス・インコーポレイテッドＡｒｃｔｕｒｕｓ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． 遺伝子サイレンシング用トランスサイレチン対立遺伝子選択的ｕｎａオリゴマー
CN110846316B (zh) * 2014-03-25 2023-10-31 阿克丘勒斯治疗公司 在基因沉默中具有降低的脱靶效应的una寡聚物
UA121656C2 (uk) 2014-05-01 2020-07-10 Айоніс Фармасьютикалз, Інк. Олігомерна сполука та спосіб лікування захворювання, пов'язаного з порушенням регуляції альтернативного шляху комплементу
PL3185957T3 (pl) 2014-08-29 2022-11-14 Alnylam Pharmaceuticals, Inc. Patisiran do zastosowania w leczeniu amyloidozy związanej z transtyretyną
US12180263B2 (en) 2014-11-06 2024-12-31 President And Fellows Of Harvard College Cells lacking B2M surface expression and methods for allogeneic administration of such cells
EP3702456A1 (en) 2014-12-24 2020-09-02 The Broad Institute, Inc. Crispr having or associated with destabilization domains
EP3277289A4 (en) 2015-04-01 2018-12-05 Arcturus Therapeutics, Inc. Therapeutic una oligomers and uses thereof
US10745702B2 (en) 2015-04-08 2020-08-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the LECT2 gene
JP6975641B2 (ja) 2015-04-13 2021-12-01 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. アンギオポエチン様３（ＡＮＧＰＴＬ３）ｉＲＮＡ組成物およびそれらの使用方法
CN107921148A (zh) 2015-05-08 2018-04-17 哈佛学院校长同事会 通用供体干细胞和相关方法
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
WO2017015671A1 (en) * 2015-07-23 2017-01-26 Arcturus Therapeutics, Inc. Compositions for treating amyloidosis
HUE051998T2 (hu) 2015-07-31 2021-04-28 Alnylam Pharmaceuticals Inc Transztiretin (TTR) iRNS készítmények és eljárások azok alkalmazása TTR-asszociált betegségek kezelésére vagy megelõzésére
IL296377A (en) 2016-03-07 2022-11-01 Arrowhead Pharmaceuticals Inc Targeting ligands for therapeutic compounds and uses of same
CN116942841A (zh) 2016-09-02 2023-10-27 箭头药业股份有限公司 靶向配体
WO2018067900A1 (en) 2016-10-06 2018-04-12 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
CN110177544A (zh) 2016-11-29 2019-08-27 普尔泰克健康有限公司 用于递送治疗剂的外泌体
IL268683B2 (en) 2017-02-17 2023-04-01 Eidos Therapeutics Inc Processes for preparing ag-10, its intermediates, and salts thereof
WO2019060442A1 (en) 2017-09-19 2019-03-28 Alnylam Pharmaceuticals, Inc. COMPOSITIONS AND METHODS FOR TREATMENT OF TRANSTHYRETIN MEDIATED AMYLOSIS (TTR)
AU2018338790B2 (en) 2017-09-29 2022-09-15 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized TTR locus and methods of use
AU2018338787C1 (en) 2017-09-29 2025-10-23 Intellia Therapeutics, Inc. Compositions and methods for TTR gene editing and treating ATTR amyloidosis
MA52137A (fr) * 2018-03-23 2021-01-27 Eidos Therapeutics Inc Méthodes de traitement de l'amylose ttr à l'aide d'ag10
EP4647068A2 (en) 2018-08-17 2025-11-12 Eidos Therapeutics, Inc. Formulations of ag10
EA202190688A1 (ru) 2018-10-09 2021-06-07 Дзе Юниверсити Оф Бритиш Коламбиа Композиции и системы, содержащие трансфекционно-компетентные везикулы, не содержащие органических растворителей и детергентов, и связанные с ними способы
US12268669B2 (en) 2018-12-20 2025-04-08 Pfizer Inc. Pharmaceutical compositions and methods comprising a combination of a benzoxazole transthyretin stabilizer and an additional therapeutic agent
KR20220016869A (ko) 2019-06-04 2022-02-10 리제너론 파마슈티칼스 인코포레이티드 베타-슬립 돌연변이를 갖는 인간화 ttr 좌위를 포함하는 비-인간 동물 및 사용 방법
WO2021016075A1 (en) 2019-07-19 2021-01-28 Flagship Pioneering Innovations Vi, Llc Recombinase compositions and methods of use
EP4022062A1 (en) 2019-08-30 2022-07-06 Alnylam Pharmaceuticals, Inc. Neurofilament light chain (nfl) as a biomarker for transthyretin amyloidosis polyneuropathy
US12378560B2 (en) 2019-10-29 2025-08-05 Northwestern University Sequence multiplicity within spherical nucleic acids
KR20220110749A (ko) * 2019-11-06 2022-08-09 알닐람 파마슈티칼스 인코포레이티드 간외 전달
BR112022017715A2 (pt) 2020-03-04 2022-11-16 Flagship Pioneering Innovations Vi Llc Métodos e composições para modular um genoma
CA3174473A1 (en) 2020-03-06 2021-09-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin (ttr)
IL298362A (en) 2020-05-20 2023-01-01 Flagship Pioneering Innovations Vi Llc Coronavirus antigen compositions and their uses
CN116194139A (zh) 2020-05-20 2023-05-30 旗舰创业创新第六有限责任公司 免疫原性组合物及其用途
EP4158032A2 (en) 2020-05-29 2023-04-05 Flagship Pioneering Innovations VI, LLC Trem compositions and methods relating thereto
EP4158031A1 (en) 2020-05-29 2023-04-05 Flagship Pioneering Innovations VI, LLC Trem compositions and methods relating thereto
IL300947A (en) 2020-09-03 2023-04-01 Flagship Pioneering Innovations Vi Llc Immunogenic compositions and uses thereof
CN117098541A (zh) 2020-11-25 2023-11-21 阿卡格拉医药公司 用于递送核酸的脂质纳米粒及相关使用方法
WO2022112919A1 (en) 2020-11-25 2022-06-02 Pfizer Inc. (aza)benzothiazolyl substituted pyrazole compounds
IL303886A (en) 2020-12-23 2023-08-01 Flagship Pioneering Inc Compositions of modified trems and uses thereof
US20240279653A1 (en) * 2021-02-22 2024-08-22 Alnylam Pharmaceuticals, Inc. FOLLICULIN iRNA COMPOSITIONS AND METHODS THEREOF
AU2022231003A1 (en) 2021-03-04 2023-09-14 Alnylam Pharmaceuticals, Inc. Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof
US20220325287A1 (en) 2021-03-31 2022-10-13 Flagship Pioneering Innovations V, Inc. Thanotransmission polypeptides and their use in treating cancer
EP4334448A1 (en) 2021-05-03 2024-03-13 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating transthyretin (ttr) mediated amyloidosis
WO2022260939A2 (en) 2021-06-08 2022-12-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders
US20240336945A1 (en) 2021-07-26 2024-10-10 Flagship Pioneering Innovations Vi, Llc Trem compositions and uses thereof
JP2024530018A (ja) * 2021-08-03 2024-08-14 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 トランスサイレチン（ＴＴＲ）ｉＲＮＡ組成物およびその使用方法
IL311225A (en) 2021-09-08 2024-05-01 Flagship Pioneering Innovations Vi Llc Methods and compositions for genome modulation
EP4464783A3 (en) 2021-09-17 2025-01-22 Flagship Pioneering Innovations VI, LLC Compositions and methods for producing circular polyribonucleotides
MX2024004618A (es) 2021-10-18 2024-07-12 Flagship Pioneering Innovations Vi Llc Composiciones y metodos para purificar polirribonucleotidos.
CN114058636A (zh) * 2021-11-16 2022-02-18 大连润生康泰医学检验实验室有限公司 一种转甲状腺素蛋白基因的克隆、表达与纯化方法
CN118555966A (zh) 2021-11-24 2024-08-27 旗舰创业创新六公司 免疫原性组合物及其用途
WO2023096963A1 (en) 2021-11-24 2023-06-01 Flagship Pioneering Innovations Vi, Llc Varicella-zoster virus immunogen compositions and their uses
EP4436984A1 (en) 2021-11-24 2024-10-02 Flagship Pioneering Innovations VI, LLC Coronavirus immunogen compositions and their uses
US20250051386A1 (en) 2021-12-22 2025-02-13 Flagship Pioneering Innovations Vi, Llc Compositions and methods for purifying polyribonucleotides
CA3241026A1 (en) 2021-12-23 2023-06-29 Flagship Pioneering Innovations Vi, Llc Circular polyribonucleotides encoding antifusogenic polypeptides
EP4504252A2 (en) 2022-04-08 2025-02-12 Flagship Pioneering Innovations VII, LLC Vaccines and related methods
CA3257006A1 (en) 2022-05-09 2023-11-16 Flagship Pioneering Innovations Vi, Llc TREM COMPOSITIONS AND METHODS OF USE FOR TREATING PROLIFERATIVE DISORDERS
WO2023220729A2 (en) 2022-05-13 2023-11-16 Flagship Pioneering Innovations Vii, Llc Double stranded dna compositions and related methods
AU2023275780A1 (en) 2022-05-25 2024-12-05 Akagera Medicines, Inc. Lipid nanoparticles for delivery of nucleic acids and methods of use thereof
EP4544043A1 (en) 2022-06-22 2025-04-30 Flagship Pioneering Innovations VI, LLC Compositions of modified trems and uses thereof
EP4565604A2 (en) 2022-08-01 2025-06-11 Flagship Pioneering Innovations VII, LLC Immunomodulatory proteins and related methods
EP4569112A1 (en) 2022-08-12 2025-06-18 Remix Therapeutics Inc. Methods and compositions for modulating splicing at alternative splice sites
WO2024077191A1 (en) 2022-10-05 2024-04-11 Flagship Pioneering Innovations V, Inc. Nucleic acid molecules encoding trif and additionalpolypeptides and their use in treating cancer
KR20250099195A (ko) 2022-10-31 2025-07-01 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 폴리리보뉴클레오티드를 정제하기 위한 조성물 및 방법
WO2024098061A2 (en) 2022-11-04 2024-05-10 Genkardia Inc. Oligonucleotide-based therapeutics targeting cyclin d2 for the treatment of heart failure
WO2024102799A1 (en) 2022-11-08 2024-05-16 Flagship Pioneering Innovations Vi, Llc Compositions and methods for producing circular polyribonucleotides
EP4619524A1 (en) 2022-11-18 2025-09-24 Genkardia Inc. Methods and compositions for preventing, treating, or reversing cardiac diastolic dysfunction
WO2024129874A1 (en) * 2022-12-13 2024-06-20 Sirnaomics, Inc. Products and compositions
WO2024129988A1 (en) 2022-12-14 2024-06-20 Flagship Pioneering Innovations Vii, Llc Compositions and methods for delivery of therapeutic agents to bone
US20240252520A1 (en) 2023-01-09 2024-08-01 Beth Israel Deaconess Medical Center, Inc. Therapeutic agents and their use for treating chronic wounds
US20240238473A1 (en) 2023-01-09 2024-07-18 Beth Israel Deaconess Medical Center, Inc. Recombinant nucleic acid molecules and their use in wound healing
US20240269251A1 (en) 2023-01-09 2024-08-15 Flagship Pioneering Innovations V, Inc. Genetic switches and their use in treating cancer
IL322468A (en) 2023-02-13 2025-09-01 Flagship Pioneering Innovations Vii Llc Ionizable lipids containing degradable crosslinkers and lipid carriers for therapeutic compositions
TW202446956A (zh) 2023-02-17 2024-12-01 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 包含經修飾的胞嘧啶的ｄｎａ組成物
IL322201A (en) 2023-02-17 2025-09-01 Flagship Pioneering Innovations Vii Llc DNA structures containing modified uracil
WO2024192422A1 (en) 2023-03-15 2024-09-19 Flagship Pioneering Innovations Vi, Llc Immunogenic compositions and uses thereof
CN121127594A (zh) 2023-03-15 2025-12-12 旗舰创业创新第六有限责任公司 包含多核糖核苷酸的组合物及其用途
KR20250171373A (ko) 2023-04-12 2025-12-08 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 미스센스 돌연변이 교정용 trem
WO2025006684A1 (en) 2023-06-28 2025-01-02 Flagship Pioneering Innovations Vi, Llc Circular polyribonucleotides encoding antifusogenic polypeptides
WO2025042786A1 (en) 2023-08-18 2025-02-27 Flagship Pioneering Innovations Vi, Llc Compositions comprising circular polyribonucleotides and uses thereof
WO2025064475A2 (en) 2023-09-18 2025-03-27 Flagship Pioneering Innovations Vii, Llc Ionizable lipidoid compositions and therapeutic uses thereof
WO2025098117A1 (zh) * 2023-11-06 2025-05-15 成都倍特药业股份有限公司 一种抑制甲状腺素转运蛋白(TTR)表达的RNAi试剂、组合物及应用
WO2025106670A1 (en) 2023-11-14 2025-05-22 Flagship Pioneering Innovations Vii, Llc Ionizable lipidoid compositions and therapeutic uses thereof
WO2025210133A1 (en) 2024-04-03 2025-10-09 Deep Piction Gmbh Hybrid lipid nanoparticles for targeted delivery

Family Cites Families (256)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US513030A (en) 1894-01-16 Machine for waxing or coating paper
US564562A (en) 1896-07-21 Joseph p
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4522808A (en) 1980-08-15 1985-06-11 Societe Anonyme Dite: L'oreal Anti-sunburn compositions containing 2-phenyl-indole derivatives
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
US4534899A (en) 1981-07-20 1985-08-13 Lipid Specialties, Inc. Synthetic phospholipid compounds
US4426330A (en) 1981-07-20 1984-01-17 Lipid Specialties, Inc. Synthetic phospholipid compounds
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
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
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
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
IL79289A (en) 1985-07-05 1992-01-15 Whitehead Biomedical Inst Introduction and expression of foreign genetic material into keratinocytes using a recombinant retrovirus
US5139941A (en) 1985-10-31 1992-08-18 University Of Florida Research Foundation, Inc. AAV transduction vectors
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
US4920016A (en) 1986-12-24 1990-04-24 Linear Technology, Inc. Liposomes with enhanced circulation time
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
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
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
CA1340032C (en) 1987-06-24 1998-09-08 Jim Haralambidis Lucleoside derivatives
JP3015383B2 (ja) 1987-09-11 2000-03-06 ホワイトヘツド・インスチチユート・フオー・バイオメデイカル・リサーチ 形質導入した線維芽およびそれらの使用
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
EP0391960B1 (en) 1987-12-11 1994-08-17 Whitehead Institute For Biomedical Research Genetic modification of endothelial cells
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
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
JPH03503894A (ja) 1988-03-25 1991-08-29 ユニバーシィティ　オブ　バージニア　アランミ　パテンツ　ファウンデイション オリゴヌクレオチド　ｎ‐アルキルホスホラミデート
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
GB8824593D0 (en) 1988-10-20 1988-11-23 Royal Free Hosp School Med Liposomes
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
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
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5356633A (en) 1989-10-20 1994-10-18 Liposome Technology, Inc. Method of treatment of inflamed tissues
US5225212A (en) 1989-10-20 1993-07-06 Liposome Technology, Inc. Microreservoir liposome composition and method
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
DE69034150T2 (de) 1989-10-24 2005-08-25 Isis Pharmaceuticals, Inc., Carlsbad 2'-Modifizierte Oligonukleotide
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
AU7579991A (en) 1990-02-20 1991-09-18 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
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
US5665710A (en) 1990-04-30 1997-09-09 Georgetown University Method of making liposomal oligodeoxynucleotide compositions
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
DK0455905T3 (da) 1990-05-11 1998-12-07 Microprobe Corp Dipsticks til nukleinsyrehybridiseringsassays og fremgangsmåde til kovalent immobilisering af oligonukleotider
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
WO1992002258A1 (en) 1990-07-27 1992-02-20 Isis Pharmaceuticals, Inc. Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside 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
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
PT98562B (pt) 1990-08-03 1999-01-29 Sanofi Sa Processo para a preparacao de composicoes que compreendem sequencias de nucleo-sidos com cerca de 6 a cerca de 200 bases resistentes a nucleases
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
EP0549686A4 (en) 1990-09-20 1995-01-18 Gilead Sciences Inc Modified internucleoside linkages
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
WO1992007943A1 (en) 1990-10-31 1992-05-14 Somatix Therapy Corporation Retroviral vectors useful for gene therapy
DE69132510T2 (de) 1990-11-08 2001-05-03 Hybridon, Inc. Verbindung von mehrfachreportergruppen auf synthetischen oligonukleotiden
GB9100304D0 (en) 1991-01-08 1991-02-20 Ici Plc Compound
JP3220180B2 (ja) 1991-05-23 2001-10-22 三菱化学株式会社 薬剤含有タンパク質結合リポソーム
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
EP0538194B1 (de) 1991-10-17 1997-06-04 Novartis AG Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
US5252479A (en) 1991-11-08 1993-10-12 Research Corporation Technologies, Inc. Safe vector for gene therapy
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
DE4203923A1 (de) 1992-02-11 1993-08-12 Henkel Kgaa Verfahren zur herstellung von polycarboxylaten auf polysaccharid-basis
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
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
US5478745A (en) 1992-12-04 1995-12-26 University Of Pittsburgh Recombinant viral vector system
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
JP3351476B2 (ja) 1993-01-22 2002-11-25 三菱化学株式会社 リン脂質誘導体及びそれを含有するリポソーム
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
US5395619A (en) 1993-03-03 1995-03-07 Liposome Technology, Inc. Lipid-polymer conjugates and liposomes
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
EP0691968B1 (en) 1993-03-30 1997-07-16 Sanofi Acyclic nucleoside analogs and oligonucleotide sequences containing them
HU9501974D0 (en) 1993-03-31 1995-09-28 Sterling Winthrop Inc Oligonucleotides with amide linkages replacing phosphodiester linkages
DE4311944A1 (de) 1993-04-10 1994-10-13 Degussa Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5540935A (en) 1993-12-06 1996-07-30 Nof Corporation Reactive vesicle and functional substance-fixed vesicle
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
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
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5543152A (en) 1994-06-20 1996-08-06 Inex Pharmaceuticals Corporation Sphingosomes for enhanced drug delivery
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5820873A (en) 1994-09-30 1998-10-13 The University Of British Columbia Polyethylene glycol modified ceramide lipids and liposome uses thereof
AU5545596A (en) 1995-04-28 1996-11-18 Medtronic, Inc. Intraparenchymal infusion catheter system
US20030027216A1 (en) 2001-07-02 2003-02-06 Kiernan Urban A. Analysis of proteins from biological fluids using mass spectrometric immunoassay
ES2231819T3 (es) 1995-06-07 2005-05-16 Inex Pharmaceuticals Corp Particulas de lipido-acido nucleico preparadas a traves de un intermedio complejo de lipido-acido nucleico hidrofobo y uso para transferir genes.
US7422902B1 (en) 1995-06-07 2008-09-09 The University Of British Columbia Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
US5756122A (en) 1995-06-07 1998-05-26 Georgetown University Liposomally encapsulated nucleic acids having high entrapment efficiencies, method of manufacturer and use thereof for transfection of targeted cells
US5981501A (en) 1995-06-07 1999-11-09 Inex Pharmaceuticals Corp. Methods for encapsulating plasmids in lipid bilayers
BR9609944A (pt) 1995-08-01 1999-05-18 Novartis Ag Composições de oligonucleotídeo lipossomal
US5858397A (en) 1995-10-11 1999-01-12 University Of British Columbia Liposomal formulations of mitoxantrone
US5735814A (en) 1996-04-30 1998-04-07 Medtronic, Inc. Techniques of treating neurodegenerative disorders by brain infusion
JP2002510319A (ja) 1997-07-01 2002-04-02 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 オリゴヌクレオチドの消化管を介したデリバリーのための組成物及び方法
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
AU747597B2 (en) 1998-07-20 2002-05-16 Inex Pharmaceuticals Corporation Liposomal encapsulated nucleic acid-complexes
MXPA01003643A (es) 1998-10-09 2003-07-21 Ingene Inc Produccion de adnss in vivo.
BR9914772A (pt) 1998-10-09 2001-12-11 Ingene Inc Conjunto de elementos genéticos, vetor, célulahospedeira, conjunto para a produção de umasequência de ácido nucléico, método para aprodução in vivo ou in vitro de uma sequência deácido nucléico, transcrição de cdna, molécula deácido nucléico inibidor, transcrição de mrna,molécula heteroduplex e composiçãofarmacêutica
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
AU3243300A (en) 1999-02-23 2000-09-14 Isis Pharmaceuticals, Inc. Multiparticulate formulation
DE10100586C1 (de) 2001-01-09 2002-04-11 Ribopharma Ag Verfahren zur Hemmung der Expression eines Ziegens
AU2001247951A1 (en) 2000-02-07 2001-08-14 Roche Diagnostics Corporation Novel cationic amphiphiles
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
US20030072794A1 (en) 2000-06-09 2003-04-17 Teni Boulikas Encapsulation of plasmid DNA (lipogenes™) and therapeutic agents with nuclear localization signal/fusogenic peptide conjugates into targeted liposome complexes
SI1407044T2 (en) 2000-12-01 2018-03-30 Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. Rna interference mediating small rna molecules
US20020160394A1 (en) 2001-01-24 2002-10-31 Bayer Corporation Regulation of transthyretin to treat obesity
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)
WO2003001182A2 (en) 2001-06-21 2003-01-03 The Cleveland Clinic Foundation Homocysteinylated transthyretin
US20030191056A1 (en) 2002-04-04 2003-10-09 Kenneth Walker Use of transthyretin peptide/protein fusions to increase the serum half-life of pharmacologically active peptides/proteins
KR101201664B1 (ko) 2002-08-05 2012-11-15 사일런스 테라퓨틱스 아게 신규한 형태의 간섭 ｒｎａ 분자
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)
CA2502413A1 (en) 2002-11-01 2004-05-21 The Regents Of The University Of Colorado, A Body Corporate Quantitative analysis of protein isoforms using matrix-assisted laser desorption/ionization time of flight mass spectrometry
JP2006507841A (ja) 2002-11-14 2006-03-09 ダーマコン， インコーポレイテッド 機能的ｓｉＲＮＡおよび超機能的ｓｉＲＮＡ
US9228186B2 (en) 2002-11-14 2016-01-05 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US7250496B2 (en) 2002-11-14 2007-07-31 Rosetta Genomics Ltd. Bioinformatically detectable group of novel regulatory genes and uses thereof
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
AU2004227414A1 (en) 2003-04-03 2004-10-21 Alnylam Pharmaceuticals iRNA conjugates
KR101168440B1 (ko) 2003-07-16 2012-07-27 프로티바 바이오쎄라퓨틱스, 인코포레이티드 지질 캡슐화된 간섭 ｒｎａ
US20050244869A1 (en) * 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
EP1765416A4 (en) 2004-06-03 2010-03-24 Isis Pharmaceuticals Inc DOUBLE-STRONG COMPOSITIONS WITH DIFFERENTLY MODIFIED STRANDS FOR USE IN GENE MODULATION
EP1781593B1 (en) 2004-06-07 2011-12-14 Protiva Biotherapeutics Inc. Cationic lipids and methods of use
US7799565B2 (en) 2004-06-07 2010-09-21 Protiva Biotherapeutics, Inc. Lipid encapsulated interfering RNA
US7838561B2 (en) 2004-06-14 2010-11-23 Wisconsin Alumni Research Foundation Method for preventing or treating cardiac hypertrophy
ES2246715B1 (es) * 2004-08-04 2007-05-01 Consejo Superior Investig. Cientificas Modelo animal de enfermedades neurodegenerativas, procedimiento de obtencion y aplicaciones.
CN101189343B (zh) * 2004-08-23 2011-11-16 阿尔尼拉姆药物公司 多rna聚合酶ⅲ启动子表达构建体
BRPI0520207A2 (pt) 2004-12-08 2012-09-25 Revision Therapeutics Inc uso de uma quantidade eficaz de um primeiro composto, e, medicamento sistemicamente formulado
CA2597724A1 (en) 2005-02-14 2007-08-02 Sirna Therapeutics, Inc. Cationic lipids and formulated molecular compositions containing them
EP1866414B9 (en) 2005-03-31 2012-10-03 Calando Pharmaceuticals, Inc. Inhibitors of ribonucleotide reductase subunit 2 and uses thereof
US7915230B2 (en) 2005-05-17 2011-03-29 Molecular Transfer, Inc. Reagents for transfection of eukaryotic cells
WO2007008652A2 (en) * 2005-07-08 2007-01-18 The University Of North Carolina At Chapel Hill Methods and compositions directed to dj-1 as regulator of the anti-oxidant transcription factor nrf2
CA2616877C (en) 2005-07-27 2014-01-28 Protiva Biotherapeutics, Inc. Systems and methods for manufacturing liposomes
CN101346393B (zh) 2005-11-02 2015-07-22 普洛体维生物治疗公司 修饰的siRNA分子及其应用
CN101448849B (zh) 2006-03-31 2013-08-21 阿尔尼拉姆医药品有限公司 抑制Eg5基因表达的组合物和方法
US8598333B2 (en) 2006-05-26 2013-12-03 Alnylam Pharmaceuticals, Inc. SiRNA silencing of genes expressed in cancer
EP2068886B1 (en) 2006-10-03 2013-09-18 Tekmira Pharmaceuticals Corporation Lipid containing formulations
GB0704764D0 (en) 2007-03-12 2007-04-18 Electrophoretics Ltd Isobarically labelled reagents and methods of their use
WO2009002944A1 (en) 2007-06-22 2008-12-31 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
US20090247608A1 (en) 2007-12-04 2009-10-01 Alnylam Pharmaceuticals, Inc. Targeting Lipids
CA2710713C (en) 2007-12-27 2017-09-19 Protiva Biotherapeutics, Inc. Silencing of polo-like kinase expression using interfering rna
EP2224912B1 (en) 2008-01-02 2016-05-11 TEKMIRA Pharmaceuticals 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
WO2009100390A2 (en) 2008-02-08 2009-08-13 Mayo Foundation For Medical Education And Research Classifying amyloidosis
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
TWI455944B (zh) 2008-07-01 2014-10-11 Daiichi Sankyo Co Ltd 雙股多核苷酸
US20110237646A1 (en) 2008-08-07 2011-09-29 Isis Pharmaceuticals, Inc. Modulation of transthyretin expression for the treatment of cns related disorders
CA2740000C (en) * 2008-10-09 2017-12-12 Tekmira Pharmaceuticals Corporation Improved amino lipids and methods for the delivery of nucleic acids
CA2739895C (en) 2008-10-20 2018-09-25 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin
MX353900B (es) 2008-11-07 2018-02-01 Massachusetts Inst Technology Lipidoides de aminoalcohol y usos de los mismos.
CA2743139C (en) 2008-11-10 2019-04-02 Alnylam Pharmaceuticals, Inc. Novel lipids and compositions for the delivery of therapeutics
US9493774B2 (en) 2009-01-05 2016-11-15 Rxi Pharmaceuticals Corporation Inhibition of PCSK9 through RNAi
EP3243504A1 (en) 2009-01-29 2017-11-15 Arbutus Biopharma Corporation Improved lipid formulation
KR102229618B1 (ko) 2009-05-05 2021-03-18 알닐람 파마슈티칼스 인코포레이티드 지질 조성물
NZ622843A (en) 2009-06-10 2015-10-30 Tekmira Pharmaceuticals Corp Improved lipid formulation
NZ597504A (en) 2009-06-15 2013-10-25 Alnylam Pharmaceuticals Inc Lipid formulated dsrna targeting the pcsk9 gene
WO2010147992A1 (en) 2009-06-15 2010-12-23 Alnylam Pharmaceuticals, Inc. Methods for increasing efficacy of lipid formulated sirna
JP5723378B2 (ja) 2009-11-03 2015-05-27 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． トランスサイレチン（ｔｔｒ）を阻害する脂質製剤化組成物及び方法
ES2893199T3 (es) 2010-03-29 2022-02-08 Alnylam Pharmaceuticals Inc Terapia de ARNbc para amiloidosis ocular relacionada con transtiretina (TTR)
RS56011B1 (sr) 2010-04-29 2017-09-29 Ionis Pharmaceuticals Inc Modulacija ekspresije transtiretina
CA2812046A1 (en) 2010-09-15 2012-03-22 Alnylam Pharmaceuticals, Inc. Modified irna agents
DK2632472T3 (en) 2010-10-29 2018-03-19 Sirna Therapeutics Inc RNA INTERFERENCE-MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERRING NUCLEIC ACIDS (SINA)
US9339513B2 (en) 2010-11-09 2016-05-17 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of Eg5 and VEGF genes
WO2012177906A1 (en) 2011-06-21 2012-12-27 Alnylam Pharmaceuticals, Inc. Assays and methods for determining activity of a therapeutic agent in a subject
SI3366775T2 (sl) 2011-11-18 2025-12-31 Alnylam Pharmaceuticals, Inc. Modificirana sredstva RNAI
US9399775B2 (en) 2011-11-18 2016-07-26 Alnylam Pharmaceuticals, Inc. RNAi agents, compositions and methods of use thereof for treating transthyretin (TTR) associated diseases
US9708607B2 (en) 2012-08-03 2017-07-18 Alnylam Pharmaceuticals, Inc. Modified RNAi agents
WO2015042564A1 (en) 2013-09-23 2015-03-26 Alnylam Pharmaceuticals, Inc. Methods for treating or preventing transthyretin (ttr) associated diseases
AU2014360314B2 (en) 2013-12-06 2018-04-26 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of transthyretin (TTR) by double-stranded RNA
KR102005337B1 (ko) * 2014-01-09 2019-07-30 에스케이하이닉스 주식회사 전압 변환 장치
IL316808A (en) 2014-08-20 2025-01-01 Alnylam Pharmaceuticals Inc Modified double-stranded RNA materials and their uses
PL3185957T3 (pl) 2014-08-29 2022-11-14 Alnylam Pharmaceuticals, Inc. Patisiran do zastosowania w leczeniu amyloidozy związanej z transtyretyną
HUE051998T2 (hu) 2015-07-31 2021-04-28 Alnylam Pharmaceuticals Inc Transztiretin (TTR) iRNS készítmények és eljárások azok alkalmazása TTR-asszociált betegségek kezelésére vagy megelõzésére
EP3555292A1 (en) 2016-12-16 2019-10-23 Alnylam Pharmaceuticals, Inc. Methods for treating or preventing ttr-associated diseases using transthyretin (ttr) irna compositions
WO2019060442A1 (en) 2017-09-19 2019-03-28 Alnylam Pharmaceuticals, Inc. COMPOSITIONS AND METHODS FOR TREATMENT OF TRANSTHYRETIN MEDIATED AMYLOSIS (TTR)
US10799808B2 (en) 2018-09-13 2020-10-13 Nina Davis Interactive storytelling kit
JP7470107B2 (ja) 2018-09-28 2024-04-17 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 トランスサイレチン（ＴＴＲ）ｉＲＮＡ組成物及びＴＴＲ関連眼疾患を治療又は予防するためのその使用方法
EP4022062A1 (en) 2019-08-30 2022-07-06 Alnylam Pharmaceuticals, Inc. Neurofilament light chain (nfl) as a biomarker for transthyretin amyloidosis polyneuropathy
EP4055165A1 (en) 2019-11-06 2022-09-14 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
CA3174473A1 (en) 2020-03-06 2021-09-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin (ttr)
EP4334448A1 (en) 2021-05-03 2024-03-13 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating transthyretin (ttr) mediated amyloidosis
WO2022260939A2 (en) 2021-06-08 2022-12-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders
JP2024530018A (ja) 2021-08-03 2024-08-14 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 トランスサイレチン（ＴＴＲ）ｉＲＮＡ組成物およびその使用方法

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