CN114854738A - 用于治疗与TGFβ1表达相关的疾病的siRNA - Google Patents
用于治疗与TGFβ1表达相关的疾病的siRNA Download PDFInfo
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Abstract
本发明属于生物领域，具体涉及一种用于治疗与TGFβ1表达相关的疾病的siRNA。首先公开了一种抑制TGFβ1基因表达的siRNA，所述siRNA包括一条正义链和一条反义链，所述正义链包括与所述反义链互补配对的互补性区域，所述反义链包括与所述正义链互补配对的互补性区域，其中所述正义链选自与SEQID NO:1‑SEQ ID NO:129中任意一条的核苷酸序列区别不多于5个核苷酸的核苷酸序列，所述反义链选自与SEQ ID NO:130‑SEQ ID NO:258中任意一条的核苷酸序列区别不多于5个核苷酸的核苷酸序列。本发明发现了新的靶向于TGFβ1基因的siRNA，可以有效的抑制TGFβ1的表达，高效特异的命中靶标。包含该siRNA的药物组合物可用于治疗增生性瘢痕、纤维化或肿瘤等疾病。
Description
技术领域
本发明属于生物领域，具体涉及一种用于治疗与TGFβ1表达相关的疾病的 siRNA。
技术背景
增生性瘢痕的病理基础是以成纤维细胞为主的细胞成分的过度增殖和以胶原为主的细胞外基质的过度沉积。其特点是损伤后炎症反应延长，导致局部成纤维细胞的血管化、细胞增生和过量胶原沉积。致病因素主要包括：代谢异常、细胞因子、低氧和自由基、基因水平变化。目前国内外治疗瘢痕多采用局部药物封闭，皮肤移植，手术切除植皮，晶体磨疤术，气囊扩张术，抗体注射,放射治疗，压迫疗法，激素疗法，硅酮类等疗法。
肿瘤的治疗方法是很多的，肿瘤分良性肿瘤和恶性肿瘤，良性肿瘤的主要治疗方法是手术治疗，经过手术治疗良性肿瘤是可以彻底治愈的，良性肿瘤也不容易复发转移。恶性肿瘤就是我们平常说的癌症。治疗的主要方法是手术治疗化疗，放疗免疫治疗，靶向药物治疗，生物治疗干细胞移植治疗，pd1治疗等等。配合中医中药治疗，中西医结合治疗效果也是比较好的。
纤维化(fibrosis)是一个医学概念，纤维化可发生于多种器官，主要病理改变为器官组织内纤维结缔组织增多，实质细胞减少，持续进展可致器官结构破坏和功能减退，乃至衰竭，严重威胁人类健康和生命。
然而现有的治疗增生性瘢痕、肿瘤或纤维化的技术在临床上都不是很成熟，疗效有待观察。而且有的所需时间长，痛苦大，容易反复，出现不良后果等，许多都不尽如人意。
发明内容
本发明发现了一种新的方法，该方法以TGFΒ1为靶点，设计小干扰核苷酸(siRNA)双链，并从中选择最有效的siRNA，将这些选定的siRNA进行修饰，或与载体(如分支肽、LNP、Galnac等)制备成纳米颗粒制剂，皮下注射治疗增生性瘢痕、肿瘤或纤维化。
具体的，本发明的技术方案如下：
本发明第一个方面公开了一种抑制TGFβ1基因表达的siRNA，所述siRNA 包括一条正义链和一条反义链，所述反义链包括与所述正义链互补配对的互补性区域，所述正义链包括与所述反义链互补配对的互补性区域，所述正义链选自与SEQ ID NO:1-SEQ ID NO:129中任意一条的核苷酸序列区别不多于5个核苷酸的核苷酸序列，所述反义链选自与SEQID NO:130-SEQ ID NO:258中任意一条的核苷酸序列区别不多于5个核苷酸的核苷酸序列。
本发明第二个方面公开了一种TGFβ1基因沉默试剂盒，所述试剂盒包括上述的siRNA。
本发明第三个方面公开了一种抑制TGFβ1表达的siRNA在制备治疗增生性瘢痕、纤维化或肿瘤的药物组合物中的应用。
本发明第四个方面公开了一种药物组合物，所述药物组合物包含有效量的上述的siRNA。
优选的，所述药物组合物为纳米颗粒制剂。
更优选的，所述纳米颗粒制剂包括siRNA与药物组合物载体。
本发明第五个方面公开了上述的药物组合物在制备用于治疗和/或改善与 TGFβ1表达相关的疾病的药物中的应用。
优选的，所述疾病为增生性瘢痕、纤维化或肿瘤。
本发明第六个方面公开了一产品，所述产品包括上述的药物组合物。优选的，所述产品为注射剂。
与现有技术相比，本发明至少具有以下区别技术特征：
本发明发现了新的靶向于TGFβ1基因的siRNA，可以有效的抑制TGFβ1的表达，高效特异的命中靶标。包含该siRNA的药物组合物可用于治疗增生性瘢痕、纤维化或肿瘤等疾病。
具体实施方式
下面通过详细的实施例对本申请进行进一步的阐述，应该理解，下述实施例仅是为了用于说明本申请，并不对发明内容进行限定。
实施例中所用仪器、设备、试剂均可通过各种渠道获得，例如购买得到，或可以制备而得。
实施例1
本实施例公开了siRNA体外活性检测实验方法，包括以下步骤：
细胞系选用NSFB或A549，对于NSFB细胞铺板细胞数：25000cells/孔，转染前24h铺板，转染siRNA终浓度0.1nM和10nM，所述siRNA的序列如表1 所示。转染试剂RNAiMAX，转染时间48h。48h后提取RNA、反转录(500ng)、稀释10倍后qPCR检测TGFβ1表达水平。细胞系选用A549，对于A549细胞铺板细胞数：50000cells/孔，转染前24h铺板，转染终浓度0.1nM和10nM，转染试剂RNAiMAX，转染时间24h。24h后提取RNA、反转录(500ng)、稀释10 倍后qPCR检测TGFβ1表达水平，qPCR检测时以人PPIB为内参基因，引物序列如下表2所示。
表1
表2
上述实施例为本发明较佳的实施方式，但本发明的实施方式并不受上述实施例的限制，其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化，均应为等效的置换方式，都包含在本发明的保护范围之内。
序列表
<110> 纳肽得（青岛）生物医药有限公司
<120> 用于治疗与TGF β1表达相关的疾病的siRNA
<160> 262
<170> SIPOSequenceListing 1.0
<210> 1
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 1
uauucaagac cacccaccu 19
<210> 2
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 2
ccaucuaggu uauuuccgug g 21
<210> 3
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 3
cuagguuauu uccgugggau a 21
<210> 4
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 4
ggcugcggcu gcugccgcud tdt 23
<210> 5
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 5
ggacuaucca ccugcaagac u 21
<210> 6
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 6
cuauccaccu gcaagacuau c 21
<210> 7
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 7
ccugcaagac uaucgacaug g 21
<210> 8
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 8
gcaagacuau cgacauggag c 21
<210> 9
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 9
aucgacaugg agcuggugad tdt 23
<210> 140
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 140
cgacauggag cuggugaagc g 21
<210> 11
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 11
ucgacaugga gcuggugaad tdt 23
<210> 12
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 12
auggagcugg ugaagcggaa g 21
<210> 13
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 13
uggagcuggu gaagcggaag c 21
<210> 14
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 14
ggagcuggug aagcggaagc g 21
<210> 15
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 15
cuggugaagc ggaagcgcau c 21
<210> 16
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 16
uggugaagcg gaagcgcauc g 21
<210> 17
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 17
ggugaagcgg aagcgcaucg a 21
<210> 18
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 18
aggaggucac ccgcgugcua a 21
<210> 19
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 19
gguggaaacc cacaacgaaa u 21
<210> 20
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 20
gaaacccaca acgaaaucua u 21
<210> 21
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 21
cccacaacga aaucuaugac a 21
<210> 22
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 22
cacaacgaaa ucuaugacaa g 21
<210> 23
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 23
acaacgaaau cuaugacaag u 21
<210> 24
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 24
gaaaucuaug acaaguucaa g 21
<210> 25
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 25
aaaucuauga caaguucaag c 21
<210> 26
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 26
gacaaguuca agcagaguac a 21
<210> 27
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 27
gcagaguaca cacagcauau a 21
<210> 28
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 28
cacacagcau auauauguuc u 21
<210> 29
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 29
cacagcauau auauguucuu c 21
<210> 29
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 29
cacagcauau auauguucuu c 21
<210> 30
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 30
gcauauauau guucuucaac a 21
<210> 31
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 31
agagcuccga gaagcgguac c 21
<210> 32
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 32
ccgagaagcg guaccugaac c 21
<210> 33
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 33
aaguggagca gcacguggag c 21
<210> 34
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 34
aguggagcag cacguggagc u 21
<210> 35
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 35
cguggagcug uaccagaaau a 21
<210> 36
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 36
guggagcugu accagaaaua c 21
<210> 37
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 37
gagcuguacc agaaauacag c 21
<210> 38
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 38
cuguaccaga aauacagcaa c 21
<210> 39
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 39
ccagaaauac agcaacaauu c 21
<210> 40
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 40
cagaaauaca gcaacaauuc c 21
<210> 41
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 41
ugaugucacc ggaguugugc g 21
<210> 42
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 42
ucaccggagu ugugcggcag u 21
<210> 43
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 43
accggaguug ugcggcagug g 21
<210> 44
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 44
cggaguugug cggcagugg 19
<210> 45
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 45
cacugcaagu ggacaucaac g 21
<210> 46
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 46
ccaccauuca uggcaugaac c 21
<210> 47
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 47
cgcuggagag ggcccagca 19
<210> 48
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 48
ggcaccgccg agcccugga 19
<210> 49
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 49
gccgagcccu ggacaccaac u 21
<210> 50
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 50
cuggacacca acuauugcuu c 21
<210> 51
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 51
gacaccaacu auugcuucag c 21
<210> 52
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 52
gcuucagcuc cacggagaag a 21
<210> 53
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 53
ucagcuccac ggagaagaac u 21
<210> 54
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 54
agcuccacgg agaagaacug c 21
<210> 55
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 55
gcuccacgga gaagaacugc u 21
<210> 56
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 56
ccacggagaa gaacugcugc g 21
<210> 57
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 57
cggagaagaa cugcugcgug c 21
<210> 58
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 58
ggagaagaac ugcugcgugc g 21
<210> 59
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 59
gagaagaacu gcugcgugcg g 21
<210> 60
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 60
agaacugcug cgugcggcag c 21
<210> 61
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 61
gcugcgugcg gcagcuguac a 21
<210> 62
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 62
ggcagcugua cauugacuuc c 21
<210> 63
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 63
gcuggaagug gauccacgag c 21
<210> 64
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 64
ccuacauuug gagccuggac a 21
<210> 65
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 65
ccuacauuug gagccuggad tdt 23
<210> 66
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 66
cccuguacaa ccagcauaac c 21
<210> 67
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 67
gcgugccgca ggcgcuggag c 21
<210> 68
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 68
uguacuacgu gggccgcaag c 21
<210> 69
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 69
acgugggccg caagcccaag g 21
<210> 70
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 70
gccgcaagcc caagguggag c 21
<210> 71
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 71
cccaaggugg agcagcuguc c 21
<210> 72
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 72
aagguggagc agcuguccaa c 21
<210> 73
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 73
agguggagca gcuguccaac a 21
<210> 74
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 74
agguggagca gcuguccaac a 21
<210> 75
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 75
gguggagcag cuguccaaca u 21
<210> 76
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 76
guggagcagc uguccaacau g 21
<210> 77
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 77
uggagcagcu guccaacaug a 21
<210> 78
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 78
ggagcagcug uccaacauga u 21
<210> 79
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 79
gagcagcugu ccaacaugau c 21
<210> 80
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 80
agcagcuguc caacaugauc g 21
<210> 81
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 81
gcagcugucc aacaugaucg u 21
<210> 82
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 82
agcuguccaa caugaucgug c 21
<210> 83
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 83
gcuguccaac augaucgugc g 21
<210> 84
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 84
ccaacaugau cgugcgcucd tdt 23
<210> 85
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 85
ugaucgugcg cuccugcaag u 21
<210> 86
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 86
gaucgugcgc uccugcaagu g 21
<210> 87
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 87
ugaucgugcg cuccugcaad tdt 23
<210> 88
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 88
gaucgugcgc uccugcaagd tdt 23
<210> 89
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 89
cuccugcaag ugcagcugad tdt 23
<210> 91
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 91
ggcuguauuu aaggacaccd tdt 23
<210> 92
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 92
ccugucugca cuauuccuuu g 21
<210> 93
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 93
gaacacuacu guaguuagau c 21
<210> 94
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 94
cacuacugua guuagaucua u 21
<210> 95
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 95
acuacuguag uuagaucuau u 21
<210> 96
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 96
cuacuguagu uagaucuauu u 21
<210> 97
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 97
cuguaguuag aucuauuuau u 21
<210> 98
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 98
guaguuagau cuauuuauug a 21
<210> 99
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 99
gcacuguuga agugccuuac a 21
<210> 100
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 100
cuguugaagu gccuuacauu a 21
<210> 101
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 101
guugaagugc cuuacauuaa u 21
<210> 102
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 102
ccuuacauua augaacucau u 21
<210> 103
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 103
cauucaguca ccauagcaac a 21
<210> 104
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 104
cagucaccau agcaacacuc u 21
<210> 105
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 105
caccauagca acacucugag a 21
<210> 106
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 106
cauagcaaca cucugagaug c 21
<210> 107
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 107
gaugcaggga cucugauaac a 21
<210> 108
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 108
ggacucugau aacacccauu u 21
<210> 109
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 109
cugauaacac ccauuuuaaa g 21
<210> 110
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 110
cuuuaguggg ggauagugaa g 21
<210> 111
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 111
gggauaguga agaagacaau a 21
<210> 112
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 112
ggauagugaa gaagacaaua a 21
<210> 113
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 113
ggaggaggga cgagcuggud tdt 23
<210> 114
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 114
gauagugaag aagacaauaa a 21
<210> 115
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 115
gaagaagaca auaaaagaua g 21
<210> 116
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 116
gaagacaaua aaagauagua g 21
<210> 117
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 117
gacaauaaaa gauaguaguu c 21
<210> 118
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 118
gaugggagga uuacuugaau c 21
<210> 119
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 119
gauuacuuga auccaggcau u 21
<210> 120
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 120
cuugaaucca ggcauuugag a 21
<210> 121
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 121
guaacauagu gagacccuau c 21
<210> 122
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 122
gugagacccu aucucuacaa a 21
<210> 123
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 123
ccuaucucua caaaacacuu u 21
<210> 124
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 124
cuaucucuac aaaacacuuu u 21
<210> 125
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 125
cucuacaaaa cacuuuuaaa a 21
<210> 126
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 126
cuacaaaaca cuuuuaaaaa a 21
<210> 127
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 127
caaaacacuu uuaaaaaaug u 21
<210> 128
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 128
cacuuuuaaa aaauguacac c 21
<210> 129
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 129
cagcuacucu ggaggcuaag g 21
<210> 130
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 130
aggugggugg ucuugaauag g 21
<210> 131
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 131
acggaaauaa ccuagauggg c 21
<210> 132
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 132
ucccacggaa auaaccuaga u 21
<210> 133
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 133
agcggcagca gccgcagccd tdt 23
<210> 134
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 134
ucuugcaggu ggauaguccc g 21
<210> 135
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 135
uagucuugca gguggauagu c 21
<210> 136
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 136
augucgauag ucuugcaggu g 21
<210> 137
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 137
uccaugucga uagucuugca g 21
<210> 138
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 138
ucaccagcuc caugucgaud tdt 23
<210> 139
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 139
cuucaccagc uccaugucga u 21
<210> 140
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 140
uucaccagcu ccaugucgad tdt 23
<210> 141
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 141
uccgcuucac cagcuccaug u 21
<210> 142
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 142
uuccgcuuca ccagcuccau g 21
<210> 143
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 143
cuuccgcuuc accagcucca u 21
<210> 144
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 144
ugcgcuuccg cuucaccagc u 21
<210> 145
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 145
augcgcuucc gcuucaccag c 21
<210> 146
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 146
gaugcgcuuc cgcuucacca g 21
<210> 147
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 147
agcacgcggg ugaccuccuu g 21
<210> 148
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 148
uucguugugg guuuccacca u 21
<210> 149
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 149
agauuucguu guggguuucc a 21
<210> 150
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 150
ucauagauuu cguugugggu u 21
<210> 151
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 151
ugucauagau uucguugugg g 21
<210> 152
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 152
uugucauaga uuucguugug g 21
<210> 153
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 153
ugaacuuguc auagauuucg u 21
<210> 154
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 154
uugaacuugu cauagauuuc g 21
<210> 155
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 155
uacucugcuu gaacuuguca u 21
<210> 156
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 156
uaugcugugu guacucugcu u 21
<210> 157
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 157
aacauauaua ugcugugugu a 21
<210> 158
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 158
agaacauaua uaugcugugu g 21
<210> 159
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 159
uugaagaaca uauauaugcu g 21
<210> 160
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 160
uaccgcuucu cggagcucug a 21
<210> 161
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 161
uucagguacc gcuucucgga g 21
<210> 162
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 162
uccacgugcu gcuccacuuu u 21
<210> 163
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 163
cuccacgugc ugcuccacuu u 21
<210> 164
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 164
uuucugguac agcuccacgu g 21
<210> 165
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 165
auuucuggua cagcuccacg u 21
<210> 166
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 166
uguauuucug guacagcucc a 21
<210> 167
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 167
ugcuguauuu cugguacagc u 21
<210> 168
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 168
auuguugcug uauuucuggu a 21
<210> 169
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 169
aauuguugcu guauuucugg u 21
<210> 170
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 170
cacaacuccg gugacaucaa a 21
<210> 171
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 171
ugccgcacaa cuccggugac a 21
<210> 172
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 172
acugccgcac aacuccggug a 21
<210> 173
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 173
ccacugccgc acaacuccgg u 21
<210> 174
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 174
uugaugucca cuugcagugu g 21
<210> 175
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 175
uucaugccau gaaugguggc c 21
<210> 176
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 176
ugcugggccc ucuccagcgg g 21
<210> 177
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 177
uccagggcuc ggcggugccg g 21
<210> 178
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 178
uuggugucca gggcucggcg g 21
<210> 179
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 179
agcaauaguu gguguccagg g 21
<210> 180
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 180
ugaagcaaua guuggugucc a 21
<210> 181
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 181
uucuccgugg agcugaagca a 21
<210> 182
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 182
uucuucuccg uggagcugaa g 21
<210> 183
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 183
aguucuucuc cguggagcug a 21
<210> 184
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 184
caguucuucu ccguggagcu g 21
<210> 185
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 185
cagcaguucu ucuccgugga g 21
<210> 186
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 186
acgcagcagu ucuucuccgu g 21
<210> 187
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 187
cacgcagcag uucuucuccg u 21
<210> 188
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 188
gcacgcagca guucuucucc g 21
<210> 189
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 189
ugccgcacgc agcaguucuu c 21
<210> 190
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 190
uacagcugcc gcacgcagca g 21
<210> 191
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 191
aagucaaugu acagcugccg c 21
<210> 192
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 192
ucguggaucc acuuccagcc g 21
<210> 193
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 193
uccaggcucc aaauguaggg g 21
<210> 194
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 194
uccaggcucc aaauguaggd tdt 23
<210> 195
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 195
uuaugcuggu uguacagggc c 21
<210> 196
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 196
uccagcgccu gcggcacgca g 21
<210> 197
<211> 20
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 197
ugcggcccac guaguacacg 20
<210> 198
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 198
uugggcuugc ggcccacgua g 21
<210> 199
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 199
uccaccuugg gcuugcggcc c 21
<210> 200
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 200
acagcugcuc caccuugggc u 21
<210> 201
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 201
uggacagcug cuccaccuug g 21
<210> 202
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 202
uuggacagcu gcuccaccuu g 21
<210> 203
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 203
uuggacagcu gcuccaccuu g 21
<210> 204
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 204
guuggacagc ugcuccaccu u 21
<210> 205
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 205
uguuggacag cugcuccacc u 21
<210> 206
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 206
auguuggaca gcugcuccac c 21
<210> 207
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 207
cauguuggac agcugcucca c 21
<210> 208
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 208
ucauguugga cagcugcucc a 21
<210> 209
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 209
aucauguugg acagcugcuc c 21
<210> 210
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 210
gaucauguug gacagcugcu c 21
<210> 211
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 211
acgaucaugu uggacagcug c 21
<210> 212
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 212
cacgaucaug uuggacagcu g 21
<210> 213
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 213
gagcgcacga ucauguuggd tdt 23
<210> 214
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 214
uugcaggagc gcacgaucau g 21
<210> 215
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 215
cuugcaggag cgcacgauca u 21
<210> 216
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 216
uugcaggagc gcacgaucad tdt 23
<210> 217
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 217
cuugcaggag cgcacgaucd tdt 23
<210> 218
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 218
ucagcugcac uugcaggagd tdt 23
<210> 219
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 219
guguccuuaa auacagcccd tdt 23
<210> 220
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 220
gguguccuua aauacagccd tdt 23
<210> 221
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 221
aaggaauagu gcagacaggc a 21
<210> 222
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 222
ucuaacuaca guaguguucc c 21
<210> 223
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 223
agaucuaacu acaguagugu u 21
<210> 224
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 224
uagaucuaac uacaguagug u 21
<210> 225
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 225
auagaucuaa cuacaguagu g 21
<210> 226
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 226
uaaauagauc uaacuacagu a 21
<210> 227
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 227
aauaaauaga ucuaacuaca g 21
<210> 228
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 228
uaaggcacuu caacagugcc c 21
<210> 229
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 229
auguaaggca cuucaacagu g 21
<210> 230
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 230
uaauguaagg cacuucaaca g 21
<210> 231
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 231
ugaguucauu aauguaaggc a 21
<210> 232
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 232
uugcuauggu gacugaauga g 21
<210> 233
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 233
aguguugcua uggugacuga a 21
<210> 234
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 234
ucagaguguu gcuaugguga c 21
<210> 235
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 235
aucucagagu guugcuaugg u 21
<210> 236
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 236
uuaucagagu cccugcaucu c 21
<210> 237
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 237
auggguguua ucagaguccc u 21
<210> 238
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 238
uuaaaauggg uguuaucaga g 21
<210> 239
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 239
ucacuauccc ccacuaaagc a 21
<210> 240
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 240
uugucuucuu cacuaucccc c 21
<210> 241
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 241
auugucuucu ucacuauccc c 21
<210> 242
<211> 23
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 242
accagcucgu cccuccuccd tdt 23
<210> 243
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 243
uauugucuuc uucacuaucc c 21
<210> 244
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 244
aucuuuuauu gucuucuuca c 21
<210> 245
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 245
acuaucuuuu auugucuucu u 21
<210> 246
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 246
acuacuaucu uuuauugucu u 21
<210> 247
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 247
uucaaguaau ccucccaucu c 21
<210> 248
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 248
ugccuggauu caaguaaucc u 21
<210> 249
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 249
ucaaaugccu ggauucaagu a 21
<210> 250
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 250
uagggucuca cuauguuacc c 21
<210> 251
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 251
uguagagaua gggucucacu a 21
<210> 252
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 252
aguguuuugu agagauaggg u 21
<210> 253
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 253
aaguguuuug uagagauagg g 21
<210> 254
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 254
uuaaaagugu uuuguagaga u 21
<210> 255
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 255
auuuuuuaaa aguguuuugu a 21
<210> 256
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 256
auuuuuuaaa aguguuuugu a 21
<210> 257
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 257
uguacauuuu uuaaaagugu u 21
<210> 258
<211> 21
<212> RNA
<213> 人工序列(Artificial Sequence)
<400> 258
uuagccucca gaguagcugg g 21
<210> 259
<211> 21
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 259
ggtgatcttt ggtctcttcg g 21
<210> 260
<211> 21
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 260
tagatgctct ttcctcctgt g 21
<210> 261
<211> 20
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 261
gagcctgagg ccgactacta 20
<210> 262
<211> 20
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 262
cggagctctg atgtgttgaa 20
Claims (10)
1.一种用于抑制TGFβ1基因表达的siRNA，其特征在于，所述siRNA包括一条正义链和一条反义链，所述反义链包括与所述正义链互补配对的互补性区域，所述正义链包括与所述反义链互补配对的互补性区域，所述正义链选自与SEQ ID NO:1-SEQ ID NO:129中任意一条的核苷酸序列区别不多于5个核苷酸的核苷酸序列，所述反义链选自与SEQ ID NO:130-SEQ ID NO:258中任意一条的核苷酸序列区别不多于5个核苷酸的核苷酸序列。
2.一种TGFβ1基因沉默试剂盒，其特征在于，所述试剂盒包括权利要求1所述的siRNA。
3.一种抑制TGFβ1基因表达的siRNA在制备治疗增生性瘢痕、纤维化或肿瘤的药物组合物中的应用。
4.一种药物组合物，其特征在于，所述药物组合物包含有效量的权利要求1所述的siRNA。
5.根据权利要求4所述的药物组合物，其特征在于，所述药物组合物包含药学上可接受的赋形剂。
6.根据权利要求5所述的药物组合物，其特征在于，所述药物组合物为纳米颗粒制剂。
7.根据权利要求6所述的药物组合物，其特征在于，所述纳米颗粒制剂包括siRNA与药物组合物载体。
8.根据权利要求5-7任一项所述的药物组合物在制备用于治疗和/或改善与TGFβ1表达相关的疾病的药物中的应用。
9.根据权利要求8所述的应用，其特征在于，所述疾病为增生性瘢痕、纤维化或肿瘤。
10.一种产品，所述产品包括权利要求5-7任一项所述的药物组合物。
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Citations (5)
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|---|---|---|---|---|
| CN1989244A (zh) * | 2004-02-09 | 2007-06-27 | 瑞吉恩股份有限公司 | 用于治疗cns病症的tgf－r信号传递抑制剂 |
| CN101489572A (zh) * | 2006-07-12 | 2009-07-22 | 亚利桑那州董事会代表的亚利桑那州大学 | 治疗和抑制纤维化疾病和瘢痕疙瘩的方法 |
| US20100319074A1 (en) * | 2007-11-06 | 2010-12-16 | Sir Naomics, Inc. | Multi-targeted rnai therapeutics for scarless wound healing of skin |
| US20160168565A1 (en) * | 2013-08-05 | 2016-06-16 | Centre National de la Recherche Scienctifique-CNRS | Molecular targets for the prevention and/or treatment of fibrosis, hypertrophic scars or keloids |
| CN110042099A (zh) * | 2010-03-24 | 2019-07-23 | 菲奥医药公司 | 皮肤与纤维化症候中的rna干扰 |
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2021
- 2021-02-04 CN CN202110155703.1A patent/CN114854738A/zh active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1989244A (zh) * | 2004-02-09 | 2007-06-27 | 瑞吉恩股份有限公司 | 用于治疗cns病症的tgf－r信号传递抑制剂 |
| CN101489572A (zh) * | 2006-07-12 | 2009-07-22 | 亚利桑那州董事会代表的亚利桑那州大学 | 治疗和抑制纤维化疾病和瘢痕疙瘩的方法 |
| US20100319074A1 (en) * | 2007-11-06 | 2010-12-16 | Sir Naomics, Inc. | Multi-targeted rnai therapeutics for scarless wound healing of skin |
| CN110042099A (zh) * | 2010-03-24 | 2019-07-23 | 菲奥医药公司 | 皮肤与纤维化症候中的rna干扰 |
| US20160168565A1 (en) * | 2013-08-05 | 2016-06-16 | Centre National de la Recherche Scienctifique-CNRS | Molecular targets for the prevention and/or treatment of fibrosis, hypertrophic scars or keloids |
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