JP2009535045A5 - - Google Patents
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- JP2009535045A5 JP2009535045A5 JP2009508205A JP2009508205A JP2009535045A5 JP 2009535045 A5 JP2009535045 A5 JP 2009535045A5 JP 2009508205 A JP2009508205 A JP 2009508205A JP 2009508205 A JP2009508205 A JP 2009508205A JP 2009535045 A5 JP2009535045 A5 JP 2009535045A5
- Authority
- JP
- Japan
- Prior art keywords
- sirna
- nucleotides
- alkyl
- modification
- strand
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 108020004459 Small interfering RNA Proteins 0.000 claims description 110
- 125000003729 nucleotide group Chemical group 0.000 claims description 22
- 239000002773 nucleotide Substances 0.000 claims description 20
- 210000002966 serum Anatomy 0.000 claims description 16
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 13
- 238000012986 modification Methods 0.000 claims description 10
- 230000004048 modification Effects 0.000 claims description 10
- 210000004211 gastric acid Anatomy 0.000 claims description 5
- 238000007912 intraperitoneal administration Methods 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 8
- 238000003556 assay Methods 0.000 claims 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 230000000295 complement effect Effects 0.000 claims 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000001802 infusion Methods 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000007913 intrathecal administration Methods 0.000 claims 1
- 239000002777 nucleoside Substances 0.000 claims 1
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims 1
- 125000002652 ribonucleotide group Chemical group 0.000 claims 1
- 239000007921 spray Substances 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 239000004055 small Interfering RNA Substances 0.000 description 73
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 10
- 238000011534 incubation Methods 0.000 description 8
- 238000004255 ion exchange chromatography Methods 0.000 description 8
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 7
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 230000000968 intestinal effect Effects 0.000 description 7
- 238000010172 mouse model Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 230000033115 angiogenesis Effects 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 230000030279 gene silencing Effects 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 238000012226 gene silencing method Methods 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 210000001853 liver microsome Anatomy 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 3
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 3
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 238000000119 electrospray ionisation mass spectrum Methods 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000032361 posttranscriptional gene silencing Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 238000010200 validation analysis Methods 0.000 description 2
- 102000018616 Apolipoproteins B Human genes 0.000 description 1
- 108010027006 Apolipoproteins B Proteins 0.000 description 1
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101000874159 Mus musculus Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial Proteins 0.000 description 1
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 210000001650 focal adhesion Anatomy 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 238000013413 tumor xenograft mouse model Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0608838.9A GB0608838D0 (en) | 2006-05-04 | 2006-05-04 | Organic compounds |
| PCT/EP2007/003867 WO2007128477A2 (en) | 2006-05-04 | 2007-05-02 | SHORT INTERFERING RIBONUCLEIC ACID (siRNA) FOR ORAL ADMINISTRATION |
Related Child Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012200083A Division JP2013005812A (ja) | 2006-05-04 | 2012-09-12 | 経口投与用の低分子干渉リボ核酸（ｓｉＲＮＡ） |
| JP2012200081A Division JP2013005811A (ja) | 2006-05-04 | 2012-09-12 | 経口投与用の低分子干渉リボ核酸（ｓｉＲＮＡ） |
| JP2013035574A Division JP2013128488A (ja) | 2006-05-04 | 2013-02-26 | 経口投与用の低分子干渉リボ核酸（ｓｉＲＮＡ） |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009535045A JP2009535045A (ja) | 2009-10-01 |
| JP2009535045A5 true JP2009535045A5 (https=) | 2012-01-05 |
Family
ID=36603932
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009508205A Pending JP2009535045A (ja) | 2006-05-04 | 2007-05-02 | 経口投与用の低分子干渉リボ核酸（ｓｉＲＮＡ） |
| JP2012200083A Pending JP2013005812A (ja) | 2006-05-04 | 2012-09-12 | 経口投与用の低分子干渉リボ核酸（ｓｉＲＮＡ） |
| JP2012200081A Pending JP2013005811A (ja) | 2006-05-04 | 2012-09-12 | 経口投与用の低分子干渉リボ核酸（ｓｉＲＮＡ） |
| JP2013035574A Pending JP2013128488A (ja) | 2006-05-04 | 2013-02-26 | 経口投与用の低分子干渉リボ核酸（ｓｉＲＮＡ） |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012200083A Pending JP2013005812A (ja) | 2006-05-04 | 2012-09-12 | 経口投与用の低分子干渉リボ核酸（ｓｉＲＮＡ） |
| JP2012200081A Pending JP2013005811A (ja) | 2006-05-04 | 2012-09-12 | 経口投与用の低分子干渉リボ核酸（ｓｉＲＮＡ） |
| JP2013035574A Pending JP2013128488A (ja) | 2006-05-04 | 2013-02-26 | 経口投与用の低分子干渉リボ核酸（ｓｉＲＮＡ） |
Country Status (14)
| Country | Link |
|---|---|
| US (6) | US8084600B2 (https=) |
| EP (7) | EP2765196A1 (https=) |
| JP (4) | JP2009535045A (https=) |
| KR (4) | KR101378199B1 (https=) |
| CN (2) | CN101437944B (https=) |
| AU (1) | AU2007247458B2 (https=) |
| BR (1) | BRPI0711555A2 (https=) |
| CA (4) | CA2846756A1 (https=) |
| ES (2) | ES2595079T3 (https=) |
| GB (1) | GB0608838D0 (https=) |
| IN (3) | IN2014DN10849A (https=) |
| MX (1) | MX2008014007A (https=) |
| RU (2) | RU2008147665A (https=) |
| WO (1) | WO2007128477A2 (https=) |
Families Citing this family (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1845993B (zh) | 2003-08-28 | 2010-06-23 | 诺瓦提斯公司 | 具有平端和3＇修饰的干扰rna双链体 |
| GB0608838D0 (en) | 2006-05-04 | 2006-06-14 | Novartis Ag | Organic compounds |
| AR067997A1 (es) * | 2007-08-24 | 2009-10-28 | Novartis Ag | Compuestos organicos |
| RU2572826C2 (ru) | 2008-12-02 | 2016-01-20 | Чиралджен, Лтд. | Способ синтеза модифицированных по атому фосфора нуклеиновых кислот |
| US8309530B2 (en) | 2009-02-04 | 2012-11-13 | Washington State University | Compositions and methods for modulating ghrelin-mediated conditions |
| WO2010111891A1 (zh) | 2009-04-03 | 2010-10-07 | 北京大学 | 修饰的寡聚核酸分子及其制备方法和应用 |
| CA2767253A1 (en) | 2009-07-06 | 2011-01-13 | Ontorii, Inc. | Novel nucleic acid prodrugs and methods of use thereof |
| EP3000885B1 (en) | 2009-12-18 | 2018-07-25 | Arrowhead Pharmaceuticals, Inc. | Organic compositions to treat hsf1-related diseases |
| WO2011076807A2 (en) | 2009-12-23 | 2011-06-30 | Novartis Ag | Lipids, lipid compositions, and methods of using them |
| WO2011084193A1 (en) | 2010-01-07 | 2011-07-14 | Quark Pharmaceuticals, Inc. | Oligonucleotide compounds comprising non-nucleotide overhangs |
| JP2013519869A (ja) | 2010-02-10 | 2013-05-30 | ノバルティス アーゲー | 筋肉成長のための方法および化合物 |
| CA3098080A1 (en) | 2010-04-23 | 2011-10-27 | Arrowhead Research Corporation | Organic compositions to treat beta-enac-related diseases |
| ES2372237B1 (es) * | 2010-04-27 | 2013-01-24 | Consejo Superior De Investigaciones Científicas (Csic) | Oligonucleótidos modificados como reguladores de la expresión génica. |
| JP5868324B2 (ja) | 2010-09-24 | 2016-02-24 | 株式会社Wave Life Sciences Japan | 不斉補助基 |
| DK2631291T3 (da) | 2010-10-22 | 2019-06-11 | Olix Pharmaceuticals Inc | Nukleinsyremolekyler, der inducerer rna-interferens, og anvendelser deraf |
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| CN102719434A (zh) * | 2011-03-31 | 2012-10-10 | 百奥迈科生物技术有限公司 | 抑制rna干扰脱靶效应的特异性修饰 |
| AU2012284265B2 (en) | 2011-07-19 | 2017-08-17 | Wave Life Sciences Ltd. | Methods for the synthesis of functionalized nucleic acids |
| CN103930547A (zh) | 2011-09-02 | 2014-07-16 | 诺华股份有限公司 | 用于治疗hsf1相关疾病的有机组合物 |
| WO2013058306A1 (ja) * | 2011-10-19 | 2013-04-25 | 独立行政法人理化学研究所 | 機能性核酸の特異的修飾による活性化 |
| WO2013074814A2 (en) * | 2011-11-15 | 2013-05-23 | University Of Utah Research Fourdation | Morpholinos, morpholino upregulating, and associated methods |
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| US9506069B2 (en) | 2012-04-19 | 2016-11-29 | University Of Utah Research Foundation | Morpholino-mediated increase in soluble Flt-1 expression results in decreased ocular and tumor neovascularization |
| EP3272868A1 (en) | 2012-05-02 | 2018-01-24 | Arrowhead Pharmaceuticals, Inc. | Organic compositions to treat kras-related diseases |
| CN108148838A (zh) | 2012-05-22 | 2018-06-12 | 奥利克斯医药有限公司 | 具有细胞内穿透能力的诱导rna干扰的核酸分子及用途 |
| JP6453212B2 (ja) | 2012-07-13 | 2019-01-16 | ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． | キラル制御 |
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| SG11201500239VA (en) | 2012-07-13 | 2015-03-30 | Wave Life Sciences Japan | Asymmetric auxiliary group |
| CN105143450A (zh) | 2013-01-08 | 2015-12-09 | 贝尼泰克生物制药有限公司 | 年龄相关性黄斑变性治疗 |
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| WO2014144799A2 (en) * | 2013-03-15 | 2014-09-18 | New York University | siRNA TARGETING HSR1 |
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| JP6694811B2 (ja) | 2013-10-04 | 2020-05-20 | ノバルティス アーゲー | ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ |
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| EP2865756A1 (en) | 2013-10-22 | 2015-04-29 | Sylentis, S.A.U. | siRNA and their use in methods and compositions for inhibiting the expression of the FLAP gene. |
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| US9936114B2 (en) * | 2013-10-25 | 2018-04-03 | Elwha Llc | Mobile device for requesting the capture of an image |
| AU2014364520B2 (en) | 2013-12-20 | 2020-01-02 | The General Hospital Corporation | Methods and assays relating to circulating tumor cells |
| WO2015108047A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
| WO2015108048A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| JPWO2015108046A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗アレルギー作用を有するキラル核酸アジュバンド及び抗アレルギー剤 |
| ES2917473T3 (es) | 2014-01-16 | 2022-07-08 | Wave Life Sciences Ltd | Diseño quiral |
| JP2014141531A (ja) * | 2014-05-10 | 2014-08-07 | Isao Kajisa | 完成版がん根絶経口薬 |
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| WO2016022648A1 (en) * | 2014-08-07 | 2016-02-11 | Industrial Technology Research Institute | Small interfering rna and pharmaceutical composition and method for inhibiting galectin-12 expression and/or enhancing lipolysis containing the same |
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| EP3302525A2 (en) | 2015-06-05 | 2018-04-11 | Novartis AG | Methods and compositions for diagnosing, treating, and monitoring treatment of shank3 deficiency associated disorders |
| JP7402479B2 (ja) | 2015-07-14 | 2023-12-21 | トランサルガエ イスラエル リミテッド | 干渉ｒｎａ分子を送達する飼料としてのトランスジェニック微細藻類およびその使用 |
| KR102708889B1 (ko) | 2015-09-08 | 2024-09-25 | 실렌티스 에스.에이.유. | siRNA, 및 NRARP 유전자의 발현을 억제하기 위한 방법 및 조성물에서의 이의 용도 |
| EP4454637A3 (en) | 2015-11-16 | 2025-01-08 | Olix Pharmaceuticals, Inc. | Treatment of age-related macular degeneration using rna complexes that target myd88 or tlr3 |
| KR102825946B1 (ko) | 2016-02-02 | 2025-06-27 | 올릭스 주식회사 | IL4Rα, TRPA1, 또는 F2RL1을 표적화하는 RNA 복합체를 사용한 아토피 피부염 및 천식의 치료 |
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| WO2017178883A2 (en) | 2016-04-11 | 2017-10-19 | Olix Pharmaceuticals, Inc. | Treatment of idiopathic pulmonary fibrosis using rna complexes that target connective tissue growth factor |
| KR101916652B1 (ko) | 2016-06-29 | 2018-11-08 | 올릭스 주식회사 | 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도 |
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| US20180245065A1 (en) | 2016-11-01 | 2018-08-30 | Novartis Ag | Methods and compositions for enhancing gene editing |
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| WO2019014656A1 (en) | 2017-07-14 | 2019-01-17 | Han Si Ping | METALLIC OLIGONUCLEOTIDE JONCTIONS FOR THE ADMINISTRATION OF THERAPEUTIC AGENTS |
| US11530413B2 (en) | 2017-07-21 | 2022-12-20 | Novartis Ag | Compositions and methods to treat cancer |
| EP3665281A4 (en) | 2017-08-10 | 2021-05-05 | City of Hope | CONDITIONAL SIRNA AND ITS USE IN THE TREATMENT OF CARDIAC HYERTROPHY |
| US10597657B2 (en) | 2017-09-11 | 2020-03-24 | Arrowhead Pharmaceuticals, Inc. | RNAi agents and compositions for inhibiting expression of apolipoprotein C-III (APOC3) |
| EP3788138A1 (en) | 2018-05-02 | 2021-03-10 | Novartis AG | Regulators of human pluripotent stem cells and uses thereof |
| SG11202105577TA (en) | 2019-01-09 | 2021-06-29 | Arrowhead Pharmaceuticals Inc | Rnai agents for inhibiting expression of hif-2 alpha (epas1), compositions thereof, and methods of use |
| AR131406A1 (es) | 2022-12-20 | 2025-03-19 | Novartis Ag | Método de ligación de ácidos nucleicos |
| AR131405A1 (es) | 2022-12-20 | 2025-03-19 | Novartis Ag | Ligasas modificadas y usos de las mismas |
| EP4560019A1 (en) | 2023-11-22 | 2025-05-28 | Sylentis S.A.U. | Sirna and compositions for prophylactic and therapeutic treatment of ocular retinal conditions |
| EP4560020A1 (en) | 2023-11-22 | 2025-05-28 | Sylentis S.A.U. | Sirna and compositions for prophylactic and therapeutic treatment of ocular retinal conditions |
| WO2025262452A1 (en) | 2024-06-18 | 2025-12-26 | Novartis Ag | Nucleic acid ligation method |
| WO2026013628A1 (en) * | 2024-07-12 | 2026-01-15 | Novartis Ag | Double stranded rnai agents, compositions and methods of use |
| CN119040329B (zh) * | 2024-10-29 | 2025-03-18 | 南京大学 | 一种靶向胶质母细胞瘤的siRNA及其应用 |
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