WO2009029688A2 - Compositions of asymmetric interfering rna and uses thereof - Google Patents

Compositions of asymmetric interfering rna and uses thereof Download PDF

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Publication number
WO2009029688A2
WO2009029688A2 PCT/US2008/074528 US2008074528W WO2009029688A2 WO 2009029688 A2 WO2009029688 A2 WO 2009029688A2 US 2008074528 W US2008074528 W US 2008074528W WO 2009029688 A2 WO2009029688 A2 WO 2009029688A2
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strand
rna molecule
nucleotides
duplex
length
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French (fr)
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WO2009029688A3 (en
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Chiang Jia Li
Xiangao Sun
Harry Rogoff
Youzhi Li
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Sumitomo Pharma Oncology Inc
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Boston Biomedical Inc
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Priority to ES08828867.5T priority Critical patent/ES2617877T3/es
Priority to CA2735166A priority patent/CA2735166C/en
Priority to EP08828867.5A priority patent/EP2193140B1/en
Priority to DK08828867.5T priority patent/DK2193140T3/en
Priority to HK11102556.9A priority patent/HK1148534B/xx
Priority to EP21158616.9A priority patent/EP3889261A1/en
Priority to CN200880113236.9A priority patent/CN101835789B/zh
Priority to EP16187862.4A priority patent/EP3121281B1/en
Priority to JP2010523120A priority patent/JP2010537639A/ja
Publication of WO2009029688A2 publication Critical patent/WO2009029688A2/en
Publication of WO2009029688A3 publication Critical patent/WO2009029688A3/en
Anticipated expiration legal-status Critical
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    • C12N2310/00—Structure or type of the nucleic acid
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Definitions

  • RNAi therapeutics There is a need to develop novel approaches to effective RNAi in mammalian cells through a novel design of siRNAs having better efficacy and potency, rapid onset of action, better durability, and a shorter length of the RNA duplex to avoid non-specific interferon like response and to reduce the cost of synthesis for research and pharmaceutical development of RNAi therapeutics.
  • the second strand is substantially complementary to a target mRNA sequence
  • the eukaryotic cell is a mammalian cell or an avian cell.
  • the duplex RNA molecule is an isolated duplex RNA molecule.
  • the 3'-overhang and/or 5'-overhang is stabilized against degradation.
  • the duplex RNA molecule contains at least one modified nucleotide or its analogue.
  • the at least one modified nucleotide or its analogue is sugar-, backbone-, and/or base- modified ribonucleotide.
  • the backbone-modified ribonucleotide has a modification in a phosphodiester linkage with another ribonucleotide.
  • the phosphodiester linkage is modified to include at least one of a nitrogen or sulphur heteroatom.
  • the nucleotide analogue is a backbone-modified ribonucleotide containing a phosphothioate group.
  • the present invention provides a method of modifying a first duplex RNA molecule with an antisense strand and a sense strand that form a double-stranded region.
  • the method comprises, shortening the length of the sense strand so that the antisense strand has a 3'-overhang from 1-8 nucleotides and a 5'-ovcrhang from 0-8 nucleotides, and forming a second duplex RNA molecule; wherein at least one property of the first duplex RNA molecule is improved.
  • the property is selected from the group consisting of size, efficacy, potency, the speed of onset, durability, synthesis cost, off-target effects, interferon response, and delivery.
  • the present invention also provides a cell.
  • the cell comprises the expression vector.
  • the cell comprises the duplex RNA molecule.
  • the cell is a mammalian cell, avian cell, or bacterial cell.
  • Figure IB shows the structure of a duplex RNA molecule that has both a 3 '-overhang and a 5 '-overhang on the first strand, and a nick in the duplex.
  • Figure 6d shows the schematic of ⁇ -catenin mRNA cleavage site confirmed by sequencing the 5'-RACE-PCR fragment.
  • Figure 6e shows differential RISC loading efficiency of aiRNA and siRNA.
  • aiRNA or siRNA duplexes were transfected into HeIa cells 48 hours after transfection with pCMV-Ago2.
  • Ago2 was immunoprecipitated at the indicated time points following aiRNA or siRNA transfection, and northern blot analysis was performed to determine levels of Ago2/RISC associated small RNAs. Levels of Ago2 (shown below-) were determined by western blot following IP.
  • Figure 14a shows aiRNA duplex is more efficacious than siRNA in targeting ⁇ -catenin in different mammalian cell lines.
  • Figure 14b shows the western blot analysis o ⁇ Nbsl, Survivin, Parpl, p21 from cells transfected with 20 nM of the indicated aiRNA or siRNA for 48 hours.
  • the first strand is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides longer than the second strand.
  • the duplex RNA molecule comprises a double-stranded region, a blunt end, and a 5 '-overhang (see, e.g., Fig. 2A).
  • the method comprises changing the length of the antisene and/or sense strand so that the duplex RNA molecule is formed having at least one of a 3'- overhang of 1-6 nucleotides and a 5'-overhang of 1-6 nucleotides.
  • aiRNA molecules possess several advantages that should make a wider ranger of methods available for delivery purpose.
  • aiRNAs can be designed to be smaller than their siRNA and miRNA counterparts, therefore, reducing or eliminating any interferon responses.
  • aiRNAs are more potent, faster-onsetting, more efficacious and lasts longer, therefore, less amount/dosage of aiRNAs is required to achieve a therapeutic goal.
  • ds RNA double stranded RNA
  • PLR protein kinase R
  • Modification to the parental 15/21 aiRNA structure was done by altering the sense strand, anti-sense strand, or both (Table 4). Modified aiRNA duplexes were transfected into HeIa cells at 50 nM for 48 hours. Western blots for ⁇ -catenin and actin were used to examine the degree of gene silencing compared to the parental 15/21 aiRNA and to the traditional siRNA structure. aiRNA modifications were also tested which contained dual sense strand overhangs. These oligonucleotides contain a 21 base sense strand paired to differing length anti-sense strands. In addition, we also examined the activity of aiRNA oligonucleotides that have been modified with DNA bases.
  • aiRNA is more efficacious than siRNA in silencing Stat3, ⁇ -catenin, Rskl, p70S6K, Nbsl, mTOR, and EF2, and is as efficacious as siRNA in silencing NQOl, PCNA, Survivin, PTEN, Parpl, and p21. Since the target sequences were chosen based on the optimization for siRNA, it is possible that the efficacy and potency of aiRNA can be further increased by targeting sites that are optimized for aiRNA.
  • RNAi double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals.

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PCT/US2008/074528 2007-08-27 2008-08-27 Compositions of asymmetric interfering rna and uses thereof Ceased WO2009029688A2 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
ES08828867.5T ES2617877T3 (es) 2007-08-27 2008-08-27 Composiciones de ARN interferente asimétrico y uso de las mismas
CA2735166A CA2735166C (en) 2007-08-27 2008-08-27 Compositions of asymmetric interfering rna and uses thereof
EP08828867.5A EP2193140B1 (en) 2007-08-27 2008-08-27 Compositions of asymmetric interfering rna and uses thereof
DK08828867.5T DK2193140T3 (en) 2007-08-27 2008-08-27 COMPOSITIONS OF ASYMMETRIC INTERFERRING RNA AND ITS APPLICATIONS
HK11102556.9A HK1148534B (en) 2007-08-27 2008-08-27 Compositions of asymmetric interfering rna and uses thereof
EP21158616.9A EP3889261A1 (en) 2007-08-27 2008-08-27 Compositions of asymmetric interfering rna and uses thereof
CN200880113236.9A CN101835789B (zh) 2007-08-27 2008-08-27 不对称干扰rna的组合物及其用途
EP16187862.4A EP3121281B1 (en) 2007-08-27 2008-08-27 Compositions of asymmetric interfering rna and uses thereof
JP2010523120A JP2010537639A (ja) 2007-08-27 2008-08-27 非対称性干渉ｒｎａの組成物およびその使用

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US96825707P 2007-08-27 2007-08-27
US60/968,257 2007-08-27
US2975308P 2008-02-19 2008-02-19
US61/029,753 2008-02-19
US3895408P 2008-03-24 2008-03-24
US61/038,954 2008-03-24

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WO2009029688A2 true WO2009029688A2 (en) 2009-03-05
WO2009029688A3 WO2009029688A3 (en) 2009-07-02

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PCT/US2008/074531 Ceased WO2009029690A1 (en) 2007-08-27 2008-08-27 Composition of asymmetric rna duplex as microrna mimetic or inhibitor

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EP (4) EP2193140B1 (https=)
JP (7) JP2010537640A (https=)
CN (3) CN105018492B (https=)
CA (2) CA2735167A1 (https=)
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Cited By (45)

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WO2010039536A2 (en) 2008-09-23 2010-04-08 President And Fellows Of Harvard College Sirt4 and uses thereof
CN101979558A (zh) * 2010-10-28 2011-02-23 百奥迈科生物技术有限公司 一种靶向乙型肝炎病毒基因的siRNA分子及其应用
JP2011505868A (ja) * 2007-12-18 2011-03-03 ドンギ イ オフターゲット効果を極力抑えるとともに、ＲＮＡｉ機構を飽和させない新規なｓｉＲＮＡ構造及びその用途
WO2011041582A2 (en) 2009-09-30 2011-04-07 President And Fellows Of Harvard College Methods for modulation of autophagy through the modulation of autophagy-inhibiting gene products
EP2352744A4 (en) * 2008-10-15 2013-04-10 Somagenics Inc SHORT HAIR NADEL RNA FOR GENE EXPRESSION INHIBITION
JP2013514089A (ja) * 2009-12-18 2013-04-25 ダイセルナ ファーマシューティカルズ， インコーポレイテッド 遺伝子発現の特異的阻害のためのダイサー基質剤及び方法
CN103555722A (zh) * 2009-04-03 2014-02-05 戴瑟纳制药公司 利用不对称双链rna特异性抑制kras的方法和组合物
WO2014089121A3 (en) * 2012-12-03 2014-07-31 Thomas Ichim Retrograde delivery of cells and nucleic acids for treatment of cardiovascular diseases
US8871730B2 (en) 2009-07-13 2014-10-28 Somagenics Inc. Chemical modification of short small hairpin RNAs for inhibition of gene expression
US9080171B2 (en) 2010-03-24 2015-07-14 RXi Parmaceuticals Corporation Reduced size self-delivering RNAi compounds
WO2015182913A1 (ko) * 2014-05-27 2015-12-03 주식회사 제노포커스 유전자 침묵에 의한 목적 단백질의 과발현 방법
EP2953646A4 (en) * 2013-02-05 2017-02-15 1Globe Health Institute LLC Biodegradable and clinically-compatible nanop articles as drug delivery carriers
US9637742B2 (en) 2010-10-22 2017-05-02 Sungkyunkwan University Foundation For Corporate Collaboration Nucleic acid molecules inducing RNA interference, and uses thereof
WO2017100127A1 (en) 2015-12-06 2017-06-15 Boston Biomedical, Inc. ASYMMETRIC INTERFERING RNAs, AND COMPOSITIONS, USE, OR PREPARATION THEREOF
US9745574B2 (en) 2009-02-04 2017-08-29 Rxi Pharmaceuticals Corporation RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
US9938530B2 (en) 2008-09-22 2018-04-10 Rxi Pharmaceuticals Corporation RNA interference in skin indications
US9963702B2 (en) 2010-03-24 2018-05-08 Rxi Pharmaceuticals Corporation RNA interference in dermal and fibrotic indications
CN108064155A (zh) * 2014-12-26 2018-05-22 日东电工株式会社 用于p21基因调节的rna剂
WO2018098352A2 (en) 2016-11-22 2018-05-31 Jun Oishi Targeting kras induced immune checkpoint expression
US10125362B2 (en) 2012-05-22 2018-11-13 Olix Pharmaceuticals, Inc. RNA-interference-inducing nucleic acid molecule able to penetrate into cells, and use therefor
US10167471B2 (en) 2009-01-05 2019-01-01 Rxi Pharmaceuticals Corporation Inhibition of PCSK9 through RNAI
US10184124B2 (en) 2010-03-24 2019-01-22 Phio Pharmaceuticals Corp. RNA interference in ocular indications
WO2019074071A1 (ja) 2017-10-11 2019-04-18 日東電工株式会社 核酸分子発現の調節
US10266821B2 (en) 2007-08-27 2019-04-23 1Globe Health Institute Llc Compositions of asymmetric interfering RNA and uses thereof
US10358647B2 (en) 2015-12-13 2019-07-23 Nitto Denko Corporation siRNA structures for high activity and reduced off target
US10392619B2 (en) 2009-10-12 2019-08-27 Larry J. Smith Methods and compositions for modulating gene expression using oligonucleotide based drugs administered in vivo or in vitro
US10519449B2 (en) 2016-02-02 2019-12-31 Olix Pharmaceuticals, Inc. Treatment of angiogenesis-associated diseases using RNA complexes that target ANGPT2 and PDGFB
US10590423B2 (en) 2015-11-16 2020-03-17 Olix Pharmaceuticals, Inc. Treatment of age-related macular degeneration using RNA complexes that target MyD88 or TLR3
US20200123261A1 (en) * 2016-04-01 2020-04-23 Avidity Biosciences, Inc. Nucleic acid-polypeptide compositions and uses thereof
US10808247B2 (en) 2015-07-06 2020-10-20 Phio Pharmaceuticals Corp. Methods for treating neurological disorders using a synergistic small molecule and nucleic acids therapeutic approach
US10829761B2 (en) 2016-04-11 2020-11-10 Olix Pharmaceuticals, Inc. Treatment of idiopathic pulmonary fibrosis using RNA complexes that target connective tissue growth factor
US10900039B2 (en) 2014-09-05 2021-01-26 Phio Pharmaceuticals Corp. Methods for treating aging and skin disorders using nucleic acids targeting Tyr or MMP1
US10934550B2 (en) 2013-12-02 2021-03-02 Phio Pharmaceuticals Corp. Immunotherapy of cancer
US10947541B2 (en) 2016-02-02 2021-03-16 Olix Pharmaceuticals, Inc. Treatment of atopic dermatitis and asthma using RNA complexes that target IL4Rα, TRPA1, or F2RL1
US11001845B2 (en) 2015-07-06 2021-05-11 Phio Pharmaceuticals Corp. Nucleic acid molecules targeting superoxide dismutase 1 (SOD1)
US11021707B2 (en) 2015-10-19 2021-06-01 Phio Pharmaceuticals Corp. Reduced size self-delivering nucleic acid compounds targeting long non-coding RNA
US11040057B2 (en) 2016-06-29 2021-06-22 Olix Pharmaceuticals, Inc. Pharmaceutical compositions and methods for potentiating gene silencing
US11045488B2 (en) 2014-12-26 2021-06-29 Nitto Denko Corporation RNA interference agents for GST-π gene modulation
US11279934B2 (en) 2014-04-28 2022-03-22 Phio Pharmaceuticals Corp. Methods for treating cancer using nucleic acids targeting MDM2 or MYCN
WO2022175749A1 (en) 2021-02-18 2022-08-25 Oneglobe Holdings Limited Compositions for conjugating oligonucleotides and carbohydrates
WO2022256351A1 (en) 2021-05-29 2022-12-08 1Globe Health Institute Llc Asymmetric short duplex dna as a novel gene silencing technology and use thereof
US11591600B2 (en) 2017-02-10 2023-02-28 OliX Pharmaceuticals. Inc. Long double-stranded RNA for RNA interference
WO2024040531A1 (en) 2022-08-25 2024-02-29 1Globe Health Institute, Nanjing Novel compositions for conjugating oligonucleotides and carbohydrates
WO2025049599A1 (en) 2023-08-29 2025-03-06 President And Fellows Of Harvard College Methods for treating muscle-related disorders by modulating prolyl hydroxylase 3
US12544344B2 (en) 2017-04-19 2026-02-10 Phio Pharmaceuticals Corp. Topical delivery of nucleic acid compounds

Families Citing this family (102)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101631454A (zh) 2006-12-08 2010-01-20 衣阿华州立大学研究基金公司 参与硝酸盐吸收和代谢的植物基因
US8097712B2 (en) 2007-11-07 2012-01-17 Beelogics Inc. Compositions for conferring tolerance to viral disease in social insects, and the use thereof
WO2010141933A1 (en) * 2009-06-05 2010-12-09 Dicerna Pharmaceuticals, Inc. Specific inhibition of gene expression by nucleic acid containing a dicer substrate
WO2011034811A1 (en) 2009-09-17 2011-03-24 Sigma-Aldrich Co. Short rna mimetics
US8962584B2 (en) 2009-10-14 2015-02-24 Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. Compositions for controlling Varroa mites in bees
KR101237036B1 (ko) * 2009-11-04 2013-02-25 성균관대학교산학협력단 안티센스 가닥에 의한 오프-타겟 효과를 최소화한 신규한 ｓｉＲＮＡ 구조 및 그 용도
WO2011072390A1 (en) * 2009-12-16 2011-06-23 The University Of Western Ontario Compositions and methods related to mirna in diabetic conditions
ES2641642T3 (es) 2010-03-08 2017-11-10 Monsanto Technology Llc Moléculas de polinucleótido para regulación génica en plantas
HRP20182039T1 (hr) 2010-04-23 2019-02-08 Cold Spring Harbor Laboratory NOVE STRUKTURNO DIZAJNIRANE MOLEKULE shRNA
GB201006841D0 (en) * 2010-04-26 2010-06-09 Thomsen Lars Method, device and system for targetted cell lysis
WO2012140234A1 (en) 2011-04-13 2012-10-18 Vib Vzw Modulation of mirna in diseases with aberrant angiogenesis
WO2012149646A1 (en) * 2011-05-05 2012-11-08 Sunnybrook Research Institute Mirna inhibitors and their uses
US9150858B2 (en) 2011-08-04 2015-10-06 Yeda Research And Development Co. Ltd. Micro-RNAs and compositions comprising same for the treatment and diagnosis of serotonin-, adrenalin-, noradrenalin-, glutamate-, and corticotropin-releasing hormone- associated medical conditions
US10806146B2 (en) 2011-09-13 2020-10-20 Monsanto Technology Llc Methods and compositions for weed control
WO2013040057A1 (en) 2011-09-13 2013-03-21 Monsanto Technology Llc Methods and compositions for weed control
US10760086B2 (en) 2011-09-13 2020-09-01 Monsanto Technology Llc Methods and compositions for weed control
US10829828B2 (en) 2011-09-13 2020-11-10 Monsanto Technology Llc Methods and compositions for weed control
CA2851280C (en) 2011-10-11 2021-05-18 The Brigham And Women's Hospital, Inc. Micrornas in neurodegenerative disorders
JP6137484B2 (ja) * 2011-11-02 2017-05-31 公立大学法人大阪市立大学 遺伝子発現抑制用二本鎖核酸分子
WO2013138280A1 (en) * 2012-03-12 2013-09-19 Eaker Shannon IMPROVED ENGRAFTMENT POTENTIAL OF EMBRYONIC STEM CELLS AND PLURIPOTENT STEM CELLS USING MICRO RNAs
MX360866B (es) 2012-05-24 2018-11-09 A B Seeds Ltd Composiciones y métodos para silenciar la expresión genética.
CN109810977A (zh) 2012-05-26 2019-05-28 株式会社博纳克 具有递送功能的基因表达调控用单链核酸分子
ES2534210T3 (es) * 2012-08-29 2015-04-20 Chanel Parfums Beauté Inhibidores de micro-ARN para uso para prevenir y/o atenuar el envejecimiento cutáneo
US9096853B2 (en) * 2012-09-24 2015-08-04 U.S. Department Of Veterans Affairs Modified siRNA molecules incorporating 5-fluoro-2′-deoxyuridine residues to enhance cytotoxicity
EP2908853B1 (en) 2012-10-21 2018-12-05 University Of Rochester Thy1 (cd90) as a therapy to control adipose tissue accumulation
US10612019B2 (en) 2013-03-13 2020-04-07 Monsanto Technology Llc Methods and compositions for weed control
BR112015023051A2 (pt) 2013-03-13 2017-11-14 Monsanto Technology Llc método para controle de ervas daninhas, composição herbicida, cassete de expressão microbiano e método de produção de polinucleotídeo
US10568328B2 (en) 2013-03-15 2020-02-25 Monsanto Technology Llc Methods and compositions for weed control
EP2983790A2 (en) 2013-04-09 2016-02-17 Boston Biomedical, Inc. Methods for treating cancer
EP3030663B1 (en) 2013-07-19 2019-09-04 Monsanto Technology LLC Compositions and methods for controlling leptinotarsa
AU2014341879B2 (en) 2013-11-04 2020-07-23 Greenlight Biosciences, Inc. Compositions and methods for controlling arthropod parasite and pest infestations
UA119253C2 (uk) 2013-12-10 2019-05-27 Біолоджикс, Інк. Спосіб боротьби із вірусом у кліща varroa та у бджіл
CN105899663B (zh) 2013-12-26 2019-07-26 学校法人东京医科大学 用于基因表达控制的人工模拟miRNA及其用途
SG10201913570XA (en) 2013-12-27 2020-03-30 Bonac Corp Artificial match-type mirna for controlling gene expression and use therefor
WO2015108982A2 (en) 2014-01-15 2015-07-23 Monsanto Technology Llc Methods and compositions for weed control using epsps polynucleotides
WO2015118537A2 (en) 2014-02-05 2015-08-13 Yeda Research And Development Co. Ltd. Micro-rnas and compositions comprising same for the treatment and diagnosis of serotonin-, adrenalin-, noradrenalin-, glutamate-, and corticotropin-releasing hormone- associated medical conditions
TW201620525A (zh) * 2014-03-14 2016-06-16 波士頓生醫公司 使ｋ－ｒａｓ靜默之非對稱干擾ｒｎａ組成物及其使用方法
WO2015153339A2 (en) 2014-04-01 2015-10-08 Monsanto Technology Llc Compositions and methods for controlling insect pests
EP3145550B1 (en) * 2014-05-19 2019-03-27 BioNTech AG Particles comprising protamine and rna in combination with endosome destabilizing agents
CN106795515B (zh) * 2014-06-23 2021-06-08 孟山都技术公司 用于经由rna干扰调控基因表达的组合物和方法
US11807857B2 (en) 2014-06-25 2023-11-07 Monsanto Technology Llc Methods and compositions for delivering nucleic acids to plant cells and regulating gene expression
CN106604993A (zh) 2014-07-29 2017-04-26 孟山都技术公司 用于控制昆虫害虫的组合物和方法
CN119876138A (zh) 2014-11-14 2025-04-25 沃雅戈治疗公司 调节性多核苷酸
CA3193811A1 (en) 2014-11-14 2016-05-19 Voyager Therapeutics, Inc. Compositions and methods of treating amyotrophic lateral sclerosis (als)
JP6637652B2 (ja) * 2014-11-21 2020-01-29 株式会社バイオシンクタンク 抗腫瘍剤の選択方法およびその抗腫瘍剤が含有するｓｉＲＮＡ
SG11201705223XA (en) * 2014-12-27 2017-07-28 Bonac Corp NATURALLY OCCURING miRNA FOR CONTROLLING GENE EXPRESSION, AND USE OF SAME
CN108064288B (zh) 2015-01-22 2021-11-26 孟山都技术公司 用于控制叶甲属的组合物和方法
CN104673796A (zh) * 2015-02-09 2015-06-03 暨南大学 靶向hsv-1病毒ul18基因的小干扰rna及应用
WO2016149370A1 (en) * 2015-03-16 2016-09-22 MiRagen Therapeutics, Inc. Mirna mimetics and their use in treating sensory conditions
JP6602847B2 (ja) 2015-03-27 2019-11-06 株式会社ボナック デリバリー機能と遺伝子発現制御能を有する一本鎖核酸分子
EP3277811B1 (en) 2015-04-03 2020-12-23 University of Massachusetts Fully stabilized asymmetric sirna
EP3302053B1 (en) 2015-06-02 2021-03-17 Monsanto Technology LLC Compositions and methods for delivery of a polynucleotide into a plant
MX2017015618A (es) 2015-06-03 2018-08-15 Boston Biomedical Inc Composiciones que comprenden un inhibidor de la autorrenovación y diferenciación de células madre cancerosas y un agente inmunoterapéutico para su uso en el tratamiento del cáncer.
WO2016196782A1 (en) 2015-06-03 2016-12-08 Monsanto Technology Llc Methods and compositions for introducing nucleic acids into plants
MX368314B (es) 2015-06-05 2019-09-27 Miragen Therapeutics Inc Inhibidores del mir-155 para tratar linfoma cutáneo de células t (ctcl).
US10633653B2 (en) 2015-08-14 2020-04-28 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
GB201516685D0 (en) * 2015-09-21 2015-11-04 Varghese Oommen P And Oommen Oommen P Nucleic acid molecules with enhanced activity
WO2017132669A1 (en) 2016-01-31 2017-08-03 University Of Massachusetts Branched oligonucleotides
US20190192687A1 (en) * 2016-02-12 2019-06-27 The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Service Rna/dna hybrid nanoparticles modified with single stranded rna toeholds and uses thereof
CA3024448C (en) 2016-05-18 2025-09-09 Voyager Therapeutics, Inc. MODULATING POLYNUCLEOTIDES
CA3024449A1 (en) 2016-05-18 2017-11-23 Voyager Therapeutics, Inc. Compositions and methods of treating huntington's disease
JP2019519573A (ja) 2016-06-28 2019-07-11 ボストン バイオメディカル， インコーポレイテッド がんを処置するための方法
CN107630015B (zh) * 2016-07-19 2021-03-09 上海市东方医院 一种稳定的dna-rna双链结构
CA3033368A1 (en) 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
US10874688B2 (en) * 2016-10-31 2020-12-29 Gifu University Double-stranded nucleic acid molecule and use thereof
JP7106563B2 (ja) 2016-11-29 2022-07-26 スミトモ ファーマ オンコロジー， インコーポレイテッド ナフトフラン誘導体、その調製、および使用方法
AU2018216509B2 (en) * 2017-01-31 2024-02-29 Curigin Co.,Ltd. Nucleic acid simultaneously inhibiting expression of mTOR gene and STAT3 gene
WO2018160887A1 (en) * 2017-03-01 2018-09-07 Boston Biomedical, Inc. Pdl1-specific and beta-catenin-specific asymmetric interfering rna compositions, uses or preparation thereof
EP3618839A4 (en) 2017-05-05 2021-06-09 Voyager Therapeutics, Inc. COMPOSITIONS AND METHODS OF TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS (ALS)
JP2020518259A (ja) 2017-05-05 2020-06-25 ボイジャー セラピューティクス インコーポレイテッドＶｏｙａｇｅｒ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． ハンチントン病治療組成物および方法
CA3062656A1 (en) 2017-05-17 2018-11-22 Boston Biomedical, Inc. Methods for treating cancer
JP7406793B2 (ja) * 2017-06-23 2023-12-28 ユニバーシティー オブ マサチューセッツ ２テイル自己デリバリー型ｓｉＲＮＡおよび関連方法
WO2019004420A1 (ja) * 2017-06-30 2019-01-03 国立大学法人東京医科歯科大学 ヘテロ二本鎖型ａｎｔｉｍｉＲ
WO2019014656A1 (en) 2017-07-14 2019-01-17 Han Si Ping METALLIC OLIGONUCLEOTIDE JONCTIONS FOR THE ADMINISTRATION OF THERAPEUTIC AGENTS
EP3665281A4 (en) 2017-08-10 2021-05-05 City of Hope CONDITIONAL SIRNA AND ITS USE IN THE TREATMENT OF CARDIAC HYERTROPHY
WO2019079242A1 (en) 2017-10-16 2019-04-25 Voyager Therapeutics, Inc. TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS (ALS)
TW202413649A (zh) 2017-10-16 2024-04-01 美商航海家醫療公司 肌萎縮性脊髓側索硬化症(als)之治療
WO2019103581A1 (ko) * 2017-11-27 2019-05-31 (주)프로스테믹스 이중 가닥의 올리고뉴클레오티드 및 그 제조 방법
JP7506601B2 (ja) 2017-12-06 2024-06-26 アビディティー バイオサイエンシーズ，インク． 筋萎縮症と筋緊張性ジストロフィーを処置するための組成物および方法
US12083143B2 (en) 2018-04-06 2024-09-10 University Of Massachusetts MLK-regulated microRNAs in angiogenesis and tumor development
US20220110964A1 (en) * 2018-08-03 2022-04-14 Lemonex Inc. Pharmaceutical composition for preventing or treating atopic diseases
WO2020033899A1 (en) 2018-08-10 2020-02-13 University Of Massachusetts Modified oligonucleotides targeting snps
JP7627042B2 (ja) 2018-08-23 2025-02-05 ユニバーシティー オブ マサチューセッツ Ｏ－メチルリッチ完全安定化オリゴヌクレオチド
EP3877519B1 (en) 2018-11-09 2026-03-11 Ginkgo Bioworks, Inc. Biosynthesis of mogrosides
KR102321425B1 (ko) * 2019-01-18 2021-11-04 올릭스 주식회사 NRL(Neural retina leucine zipper)의 발현을 억제하는 비대칭 siRNA
CN113614232A (zh) 2019-01-18 2021-11-05 马萨诸塞大学 动态药代动力学修饰锚
WO2020226960A1 (en) * 2019-05-03 2020-11-12 Dicerna Pharmaceuticals, Inc. Double-stranded nucleic acid inhibitor molecules with shortened sense strands
MX2022001710A (es) 2019-08-09 2022-05-10 Univ Massachusetts Oligonucleótidos modificados químicamente dirigidos a los snp.
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
US11555190B2 (en) 2020-03-19 2023-01-17 Avidity Biosciences, Inc. Compositions and methods of treating Facioscapulohumeral muscular dystrophy
WO2021216548A1 (en) * 2020-04-21 2021-10-28 University Of Massachusetts Methods and compositions for treatment of age-related macular degeneration
WO2021242883A1 (en) 2020-05-26 2021-12-02 University Of Massachusetts Synthetic oligonucleotides having regions of block and cluster modifications
IL308337A (en) 2021-05-13 2024-01-01 Us Health Preparations and methods for the treatment of sickle cell disease
CN118369428A (zh) 2021-05-29 2024-07-19 强新科技国际研究院 作为新型基因沉默技术的短双链体dna及其应用
AU2022299169A1 (en) 2021-06-23 2024-02-08 Beth Israel Deaconess Medical Center, Inc. Optimized anti-flt1 oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders
CN118202046A (zh) * 2021-07-22 2024-06-14 中天(上海)生物科技有限公司 具有降低的脱靶效应的经修饰的小干扰rna分子
MX2024003266A (es) 2021-09-16 2024-04-03 Avidity Biosciences Inc Composiciones y metodos de tratamiento de la distrofia muscular facioescapulohumeral.
WO2023081500A2 (en) * 2021-11-08 2023-05-11 Dicerna Pharmaceuticals, Inc. RNAi OLIGONUCLEOTIDE CONJUGATES
WO2023207615A1 (zh) * 2022-04-26 2023-11-02 南京明德新药研发有限公司 一类含由天然核苷酸组成突出端的双链RNAi化合物
EP4630008A1 (en) * 2022-12-08 2025-10-15 1Globe Health Institute LLC Short duplex rna with interspersed deoxyribonucleotides as a gene silencing technology and use thereof
WO2025184876A1 (zh) * 2024-03-07 2025-09-12 竣莅医药科技（无锡）有限公司 一种rna干扰触发分子与对应核酸干扰药物制剂及其用途
CN118460650B (zh) * 2024-07-10 2025-02-14 凯莱英医药集团（天津）股份有限公司 一种Nedosiran的制备方法

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040259247A1 (en) 2000-12-01 2004-12-23 Thomas Tuschl Rna interference mediating small rna molecules
US20060211642A1 (en) * 2001-05-18 2006-09-21 Sirna Therapeutics, Inc. RNA inteference mediated inhibition of hepatitis C virus (HVC) gene expression using short interfering nucleic acid (siNA)
US20070042983A1 (en) * 2001-05-18 2007-02-22 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
US6962944B2 (en) 2001-07-31 2005-11-08 Arqule, Inc. Pharmaceutical compositions containing beta-lapachone, or derivatives or analogs thereof, and methods of using same
US7074824B2 (en) * 2001-07-31 2006-07-11 Arqule, Inc. Pharmaceutical compositions containing beta-lapachone, or derivatives or analogs thereof, and methods of using same
EP2305812A3 (en) * 2002-11-14 2012-06-06 Dharmacon, Inc. Fuctional and hyperfunctional sirna
US20040248299A1 (en) * 2002-12-27 2004-12-09 Sumedha Jayasena RNA interference
US20050266552A1 (en) * 2003-12-05 2005-12-01 Doench John G Reagents and methods for identification of RNAi pathway genes and chemical modulators of RNAi
WO2005079533A2 (en) * 2004-02-17 2005-09-01 University Of Massachusetts Methods and compositions for mediating gene silencing
WO2005086896A2 (en) * 2004-03-10 2005-09-22 Ulrich Thomann Delivery vectors for short interfering rna, micro-rna and antisense rna
AU2005222965B8 (en) * 2004-03-15 2010-07-01 City Of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded RNA
US20060142228A1 (en) * 2004-12-23 2006-06-29 Ambion, Inc. Methods and compositions concerning siRNA's as mediators of RNA interference
JP2010537640A (ja) 2007-08-27 2010-12-09 ボストン バイオメディカル， インコーポレイテッド マイクロｒｎａ模倣剤または阻害剤としての非対称性ｒｎａ二重鎖の組成物
KR100949791B1 (ko) * 2007-12-18 2010-03-30 이동기 오프-타겟 효과를 최소화하고 ＲＮＡｉ 기구를 포화시키지않는 신규한 ｓｉＲＮＡ 구조 및 그 용도
TW201620525A (zh) 2014-03-14 2016-06-16 波士頓生醫公司 使ｋ－ｒａｓ靜默之非對稱干擾ｒｎａ組成物及其使用方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
None
See also references of EP2193140A4

Cited By (79)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10266821B2 (en) 2007-08-27 2019-04-23 1Globe Health Institute Llc Compositions of asymmetric interfering RNA and uses thereof
JP2011505868A (ja) * 2007-12-18 2011-03-03 ドンギ イ オフターゲット効果を極力抑えるとともに、ＲＮＡｉ機構を飽和させない新規なｓｉＲＮＡ構造及びその用途
EP2222848A4 (en) * 2007-12-18 2011-06-22 Lee Dong Ki NEW SIRNA STRUCTURE FOR MINIMIZING OFF-TARGET EFFECTS AND RELAXATION OF SATURATION OF RNAI MACHINERY AND USE THEREOF
US10774330B2 (en) 2008-09-22 2020-09-15 Phio Pharmaceuticals Corp. Reduced size self-delivering RNAI compounds
US10876119B2 (en) 2008-09-22 2020-12-29 Phio Pharmaceuticals Corp. Reduced size self-delivering RNAI compounds
US11396654B2 (en) 2008-09-22 2022-07-26 Phio Pharmaceuticals Corp. Neutral nanotransporters
US9938530B2 (en) 2008-09-22 2018-04-10 Rxi Pharmaceuticals Corporation RNA interference in skin indications
US10041073B2 (en) 2008-09-22 2018-08-07 Rxi Pharmaceuticals Corporation Reduced size self-delivering RNAi compounds
US10138485B2 (en) 2008-09-22 2018-11-27 Rxi Pharmaceuticals Corporation Neutral nanotransporters
US10815485B2 (en) 2008-09-22 2020-10-27 Phio Pharmaceuticals Corp. RNA interference in skin indications
WO2010039536A2 (en) 2008-09-23 2010-04-08 President And Fellows Of Harvard College Sirt4 and uses thereof
EP2352744A4 (en) * 2008-10-15 2013-04-10 Somagenics Inc SHORT HAIR NADEL RNA FOR GENE EXPRESSION INHIBITION
US8779115B2 (en) 2008-10-15 2014-07-15 Somagenics Inc. Short hairpin RNAs for inhibition of gene expression
US10167471B2 (en) 2009-01-05 2019-01-01 Rxi Pharmaceuticals Corporation Inhibition of PCSK9 through RNAI
US10479992B2 (en) 2009-02-04 2019-11-19 Phio Pharmaceuticals Corp. RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
US9745574B2 (en) 2009-02-04 2017-08-29 Rxi Pharmaceuticals Corporation RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
US11667915B2 (en) 2009-02-04 2023-06-06 Phio Pharmaceuticals Corp. RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
CN103555722B (zh) * 2009-04-03 2016-08-31 戴瑟纳制药公司 利用不对称双链rna特异性抑制kras的方法和组合物
CN103555722A (zh) * 2009-04-03 2014-02-05 戴瑟纳制药公司 利用不对称双链rna特异性抑制kras的方法和组合物
US8871730B2 (en) 2009-07-13 2014-10-28 Somagenics Inc. Chemical modification of short small hairpin RNAs for inhibition of gene expression
US10870850B2 (en) 2009-07-13 2020-12-22 Somagenics, Inc. Chemical modification of short small hairpin RNAs for inhibition of gene expression
US9816091B2 (en) 2009-07-13 2017-11-14 Somagenics, Inc. Chemical modification of short small hairpin RNAs for inhibition of gene expression
WO2011041584A2 (en) 2009-09-30 2011-04-07 President And Fellows Of Harvard College Methods for modulation of autophagy through the modulation of autophagy-enhancing gene products
WO2011041582A2 (en) 2009-09-30 2011-04-07 President And Fellows Of Harvard College Methods for modulation of autophagy through the modulation of autophagy-inhibiting gene products
US10392619B2 (en) 2009-10-12 2019-08-27 Larry J. Smith Methods and compositions for modulating gene expression using oligonucleotide based drugs administered in vivo or in vitro
US11359201B2 (en) 2009-10-12 2022-06-14 Larry J. Smith Methods and compositions for modulating gene expression using oligonucleotide based drugs administered in vivo or in vitro
EP2513334A4 (en) * 2009-12-18 2014-01-08 Dicerna Pharmaceuticals Inc DICER SUBSTRATES AND PROCESS FOR SPECIFIC GENE EXPRESSION INHIBITION
JP2013514089A (ja) * 2009-12-18 2013-04-25 ダイセルナ ファーマシューティカルズ， インコーポレイテッド 遺伝子発現の特異的阻害のためのダイサー基質剤及び方法
US10913948B2 (en) 2010-03-24 2021-02-09 Phio Pharmaceuticals Corp. RNA interference in dermal and fibrotic indications
US9080171B2 (en) 2010-03-24 2015-07-14 RXi Parmaceuticals Corporation Reduced size self-delivering RNAi compounds
US10184124B2 (en) 2010-03-24 2019-01-22 Phio Pharmaceuticals Corp. RNA interference in ocular indications
US11584933B2 (en) 2010-03-24 2023-02-21 Phio Pharmaceuticals Corp. RNA interference in ocular indications
US10240149B2 (en) 2010-03-24 2019-03-26 Phio Pharmaceuticals Corp. Reduced size self-delivering RNAi compounds
US9963702B2 (en) 2010-03-24 2018-05-08 Rxi Pharmaceuticals Corporation RNA interference in dermal and fibrotic indications
US11118178B2 (en) 2010-03-24 2021-09-14 Phio Pharmaceuticals Corp. Reduced size self-delivering RNAI compounds
US10662430B2 (en) 2010-03-24 2020-05-26 Phio Pharmaceuticals Corp. RNA interference in ocular indications
US10829760B2 (en) 2010-10-22 2020-11-10 Olix Pharmaceuticals, Inc. Nucleic acid molecules inducing RNA interference, and uses thereof
US9637742B2 (en) 2010-10-22 2017-05-02 Sungkyunkwan University Foundation For Corporate Collaboration Nucleic acid molecules inducing RNA interference, and uses thereof
US10214744B2 (en) 2010-10-22 2019-02-26 Sungkyunkwan University Foundation For Corporate Collaboration Nucleic acid molecules inducing RNA interference, and uses thereof
CN101979558A (zh) * 2010-10-28 2011-02-23 百奥迈科生物技术有限公司 一种靶向乙型肝炎病毒基因的siRNA分子及其应用
US10125362B2 (en) 2012-05-22 2018-11-13 Olix Pharmaceuticals, Inc. RNA-interference-inducing nucleic acid molecule able to penetrate into cells, and use therefor
US10883105B2 (en) 2012-05-22 2021-01-05 Olix Pharmaceuticals, Inc. RNA-interference-inducing nucleic acid molecule able to penetrate into cells, and use therefor
WO2014089121A3 (en) * 2012-12-03 2014-07-31 Thomas Ichim Retrograde delivery of cells and nucleic acids for treatment of cardiovascular diseases
US11001840B2 (en) 2013-02-05 2021-05-11 1Globe Health Institute Llc Biodegradable and clinically-compatible nanoparticles as drug delivery carriers
EP3845248A1 (en) 2013-02-05 2021-07-07 1Globe Health Institute LLC Biodegradable and clinically-compatible nanoparticles as drug delivery carriers
EP2953646A4 (en) * 2013-02-05 2017-02-15 1Globe Health Institute LLC Biodegradable and clinically-compatible nanop articles as drug delivery carriers
US10934550B2 (en) 2013-12-02 2021-03-02 Phio Pharmaceuticals Corp. Immunotherapy of cancer
US11279934B2 (en) 2014-04-28 2022-03-22 Phio Pharmaceuticals Corp. Methods for treating cancer using nucleic acids targeting MDM2 or MYCN
WO2015182913A1 (ko) * 2014-05-27 2015-12-03 주식회사 제노포커스 유전자 침묵에 의한 목적 단백질의 과발현 방법
US10900039B2 (en) 2014-09-05 2021-01-26 Phio Pharmaceuticals Corp. Methods for treating aging and skin disorders using nucleic acids targeting Tyr or MMP1
US11926828B2 (en) 2014-09-05 2024-03-12 Phio Pharmaceuticals Corp. Methods for treating aging and skin disorders using nucleic acids targeting TYR or MMP1
US10405749B2 (en) 2014-12-26 2019-09-10 Nitto Denko Corporation RNA agents for P21 gene modulation
USRE49431E1 (en) 2014-12-26 2023-02-28 Nitto Denko Corporation RNA interference agents for GST-PI gene modulation
CN108064155A (zh) * 2014-12-26 2018-05-22 日东电工株式会社 用于p21基因调节的rna剂
CN108064155B (zh) * 2014-12-26 2021-06-08 日东电工株式会社 用于p21基因调节的rna剂
EP3236975A4 (en) * 2014-12-26 2018-09-12 Nitto Denko Corporation Rna agents for p21 gene modulation
US11045488B2 (en) 2014-12-26 2021-06-29 Nitto Denko Corporation RNA interference agents for GST-π gene modulation
US10808247B2 (en) 2015-07-06 2020-10-20 Phio Pharmaceuticals Corp. Methods for treating neurological disorders using a synergistic small molecule and nucleic acids therapeutic approach
US11001845B2 (en) 2015-07-06 2021-05-11 Phio Pharmaceuticals Corp. Nucleic acid molecules targeting superoxide dismutase 1 (SOD1)
US11021707B2 (en) 2015-10-19 2021-06-01 Phio Pharmaceuticals Corp. Reduced size self-delivering nucleic acid compounds targeting long non-coding RNA
US10590423B2 (en) 2015-11-16 2020-03-17 Olix Pharmaceuticals, Inc. Treatment of age-related macular degeneration using RNA complexes that target MyD88 or TLR3
WO2017100127A1 (en) 2015-12-06 2017-06-15 Boston Biomedical, Inc. ASYMMETRIC INTERFERING RNAs, AND COMPOSITIONS, USE, OR PREPARATION THEREOF
US10358647B2 (en) 2015-12-13 2019-07-23 Nitto Denko Corporation siRNA structures for high activity and reduced off target
US11926831B2 (en) 2015-12-13 2024-03-12 Nitto Denko Corporation SiRNA structures for high activity and reduced off target
US11390871B2 (en) 2015-12-13 2022-07-19 Nitto Denko Corporation SiRNA structures for high activity and reduced off target
US10519449B2 (en) 2016-02-02 2019-12-31 Olix Pharmaceuticals, Inc. Treatment of angiogenesis-associated diseases using RNA complexes that target ANGPT2 and PDGFB
US10947541B2 (en) 2016-02-02 2021-03-16 Olix Pharmaceuticals, Inc. Treatment of atopic dermatitis and asthma using RNA complexes that target IL4Rα, TRPA1, or F2RL1
US20200123261A1 (en) * 2016-04-01 2020-04-23 Avidity Biosciences, Inc. Nucleic acid-polypeptide compositions and uses thereof
US10829761B2 (en) 2016-04-11 2020-11-10 Olix Pharmaceuticals, Inc. Treatment of idiopathic pulmonary fibrosis using RNA complexes that target connective tissue growth factor
US11040057B2 (en) 2016-06-29 2021-06-22 Olix Pharmaceuticals, Inc. Pharmaceutical compositions and methods for potentiating gene silencing
WO2018098352A2 (en) 2016-11-22 2018-05-31 Jun Oishi Targeting kras induced immune checkpoint expression
US11591600B2 (en) 2017-02-10 2023-02-28 OliX Pharmaceuticals. Inc. Long double-stranded RNA for RNA interference
US12544344B2 (en) 2017-04-19 2026-02-10 Phio Pharmaceuticals Corp. Topical delivery of nucleic acid compounds
WO2019074071A1 (ja) 2017-10-11 2019-04-18 日東電工株式会社 核酸分子発現の調節
US11298371B2 (en) 2017-10-11 2022-04-12 Nitto Denko Corporation Regulation of nucleic acid molecule expression
WO2022175749A1 (en) 2021-02-18 2022-08-25 Oneglobe Holdings Limited Compositions for conjugating oligonucleotides and carbohydrates
WO2022256351A1 (en) 2021-05-29 2022-12-08 1Globe Health Institute Llc Asymmetric short duplex dna as a novel gene silencing technology and use thereof
WO2024040531A1 (en) 2022-08-25 2024-02-29 1Globe Health Institute, Nanjing Novel compositions for conjugating oligonucleotides and carbohydrates
WO2025049599A1 (en) 2023-08-29 2025-03-06 President And Fellows Of Harvard College Methods for treating muscle-related disorders by modulating prolyl hydroxylase 3

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