CN113271980A - 包含雄激素受体特异性序列的双链寡核苷酸构建体以及包含其的用于预防脱发和促进头发生长的组合物 - Google Patents
包含雄激素受体特异性序列的双链寡核苷酸构建体以及包含其的用于预防脱发和促进头发生长的组合物 Download PDFInfo
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Abstract
本发明涉及:一种双链寡核苷酸构建体,其具有如下形式的结构,其中亲水性物质和疏水性物质通过简单的共价键或接头介导的共价键在双链寡核苷酸的两个末端处缀合,以有效地将雄激素受体特异性寡核苷酸递送至细胞中;一种纳米颗粒,其可通过在水溶液中经由疏水性相互作用自组装所述双链寡核苷酸构建体来产生;以及一种用于预防脱发或促进头发生长的组合物,其包含所述双链寡核苷酸构建体。根据本发明的包含雄激素受体特异性寡核苷酸的所述双链寡核苷酸构建体以及包含其作为活性成分的用于预防脱发或促进头发生长的所述组合物可高效地抑制雄激素受体的表达而无副作用,因此可对预防脱发、尤其是雄激素性脱发、斑秃和休止期脱发症以及促进头发生长具有极好的效果。
Description
技术领域
本发明涉及一种包含雄激素受体特异性序列的双链寡核苷酸构建体和一种包含其的用于预防脱发和促进头发生长的组合物,并且更具体地涉及:一种双链寡核苷酸构建体,其被配置成使得亲水性物质和疏水性物质通过简单的共价键或接头介导的共价键与双链寡核苷酸的两个末端缀合,以有效地将雄激素受体特异性序列的核苷酸递送至细胞中;一种纳米颗粒,其能够通过在水溶液中经由疏水性相互作用自组装双链寡核苷酸构建体来产生;以及一种用于预防脱发和促进头发生长的组合物,其包含所述双链寡核苷酸构建体。
背景技术
头发在身体保护和外在美观的方面起着重要的作用,并且管理头发的目的是保护头皮、维持健康的头发状况、改善人们的外表等。脱发是头发根据生长周期而停止生长的自然损失,并且一般来说,严重的脱发被认为是主要在男性中发生的遗传现象。然而,近年来,环境因素的重要性已经显现,如由于工作压力、环境污染、暴露于有害环境和不正确的饮食习惯所致的脱发,并且脱发症被认为是一种疾病,其是指在应存在头发的区域没有头发的状况。脱发症被分成:瘢痕性脱发症,其中毛囊被破坏并被纤维组织替代,导致永久性脱发;以及非瘢痕性脱发症,其中组织不是纤维状的且保留了毛囊。非瘢痕性脱发症的例子包括休止期落发、遗传性雄激素性脱发症、斑秃和生长期落发。
随着时间的推移,头发经历所谓的“头发周期”,包括生长阶段、退化阶段、静止阶段和外生阶段。生长阶段的寿命通常为2至8年,一次占全部头发的约90%,并且在毛球与真皮乳头接触的下半部中,毛发生发基质细胞持续分裂,产生头发。在生长阶段之后是头发生长暂时停止的时期,称为退化阶段。此时转变到头发产生和发育停止的静止阶段,在此期间发根也发生变化,生发基质细胞和色素细胞的活动停止,并且不产生角蛋白,所以头发生长停止。在静止阶段,毛球收缩,并且头发仅在外生阶段掉落,已知在此期间蛋白酶参与其中。人们认为,雄激素、雌激素、甲状腺激素、类固醇、催乳素和生长激素可能作为控制头发生长的因素而参与其中,其中雄激素被称为最重要的调节剂。激素相关脱发的最常见的例子为分娩后暂时性脱发。在妊娠期间,雌激素增加并且头发周期中从生长阶段至静止阶段的进程受到抑制,然后在分娩之后,雌激素快速降低,并且进入静止阶段的进程加快,导致休止期落发。以这种方式,存在激素依赖性脱发症,但脱发的其他原因包括遗传因素、雄性激素、衰老、血液循环障碍、压力、超氧自由基等。在这里,应对措施可能根据这些原因而有所不同。对于由雄性激素所致的脱发,将DHT阻滞剂用作药剂,并且所述阻滞剂的基础机制是阻止睾酮通过5-α-还原酶转化为高活性二氢睾酮(DHT)。因为DHT与雄激素受体(AR)结合的能力是睾酮的至少5倍,毛囊的蛋白质合成被延迟,所以将通过阻止DHT的过度产生来阻断与雄激素受体结合的物质用作药剂(Dallob A.L.等人,1994.J.Clin.Endocrinol.Metab.79,703-709;Ellsworth,K和Harris G.,1995,Biochem.Biophys.Res.Commun.215,774-780;Kaufman KD.,2002.Mol and Cell Endocrinology.198,85-89)。
1942年,Hamilton揭露了脱发与雄性激素之间的关系。在雄激素性脱发症(AGA)中,发根细胞中存在的睾酮转化成强大的代谢物DHT,并且DHT(二氢睾酮)与毛囊中的雄激素受体(AR)结合,所以腺苷环化酶(其增强细胞内代谢)的活性被抑制,从而细胞中cAMP的浓度降低并且糖代谢下降,因此能量供应被抑制并且蛋白质合成被延迟,这缩短了毛囊的生长阶段,并且在重复此现象的过程期间,处于静止阶段的毛囊的比例增加,导致头发逐渐变得细且短。简而言之,已知发根细胞中存在的睾酮、作为与雄激素受体的过表达相关的激素组分的DHT受体以及5-α-还原酶的活性对于雄激素性脱发症的发生来说是重要的,并且还已知睾酮通过5-α-还原酶被过量产生为二氢睾酮(DHT),并且这种代谢物刺激头发周期抑制剂的产生,从而缩短生长阶段并且抑制毛囊产生头发的能力(Kaufman KD.,2002.Mol.and Cell.Endocrinology.198,89-85;Naito等人,2008.Br.J.Dermatol.159,300-305)。
已知DHT与雄激素受体(AR)结合的能力是睾酮的至少5倍,并且在雄激素特异性细胞和组织中,已知DHT比睾酮更多地参与雄激素活性。有两种亚型的5-α-还原酶负责这些代谢过程,且其作用根据组织而在一定程度上不同。1型5-α-还原酶存在于皮脂腺中,并且2型5-α-还原酶主要存在于泌尿生殖道和毛囊中。
非那雄胺和度他雄胺为靶向5-α-还原酶以抑制DHT的过量产生的药物,并且已知非那雄胺仅作用于2型5-α-还原酶并且度他雄胺作用于1型和2型5-α-还原酶,因此对前列腺相关疾病有很大影响。其中,经FDA批准作为秃发的治疗剂的药物为保发止(Propecia),其含有非那雄胺作为主要成分。迄今为止所开发的脱发预防药剂主要为单一化合物,如用于促进血液循环的米诺地尔以及作为雄性激素抑制剂的非那雄胺和度他雄胺,并且最近,FDA已批准了用于JAK抑制剂的药物(鲁索利替尼、托法替尼)。然而,寻找比上述物质更有效的物质的研究仍在继续。
所述雄激素受体为110KDa甾体受体,且其重要功能之一为转录与雄激素有关的基因。所述雄激素受体在雄性激素相关疾病中起重要作用,所述疾病如前列腺癌、前列腺增生、男性型脱发症、肌肉损失和多毛症。出于此原因,所述雄激素受体已被用作治疗男性特有的疾病(如前列腺癌和男性型秃发)的靶标。就统称为雄激素的雄性激素而言,睾酮在垂体腺、肾上腺和睾丸中产生,进入靶器官的细胞并且通过睾酮5-α-还原酶被还原成二氢睾酮(DHT),接着与所述受体结合并显示作为雄激素的作用。因此,如上所述,正在使用通过抑制5-α-还原酶将睾酮还原成DHT的作用来抑制DHT的产生的方法或者通过抑制DHT(由睾酮产生)与所述受体的结合来抑制雄激素的作用的方法寻求针对所述疾病的治疗剂的开发。
用于抑制基因表达的技术被认为在开发用于疾病治疗的治疗剂方面和靶标验证方面是重要的。特别地,自从发现了RNA干扰(下文称为‘RNAi’)的作用,已发现其作用于各种类型的哺乳动物细胞中的序列特异性mRNA(Silence of the transcripts:RNAinterference in medicine.J Mol Med(2005)83:764-773)。当将长链RNA双链递送至细胞时,递送的RNA双链通过称为dicer的内切核酸酶被加工并转化成21至23个双链(碱基对,bp)的小干扰RNA(下文称为‘siRNA’),并且siRNA与RNA诱导的沉默复合物(RISC)结合,并且因此引导(反义)链识别并降解靶mRNA,从而以序列特异性方式抑制靶基因的表达(NUCLEIC-ACID THERAPEUTICS:BASIC PRINCIPLES AND RECENT APPLICATIONS.NatureReviews Drug Discovery.2002.1,503-514)。
根据Bertrand研究人员,已报道与反义寡核苷酸(ASO)相比,针对同一靶基因的siRNA在体外和体内对mRNA的表达均具有优异的抑制作用,并且所述作用是长久的(Comparison of antisense oligonucleotides and siRNAs in cell culture and invivo.Biochem.Biophys.Res.Commun.2002.296:1000-1004)。此外,siRNA的作用机制为siRNA与靶mRNA互补地结合,以序列特异性方式调节靶基因的表达,并且与现有的基于抗体的药物或化学药物(小分子药物)相比,其具有可大大扩大适用靶标的范围的优点(Progress Towards in Vivo Use of siRNAs.MOLECULAR THERAPY.200613(4):664-670)。
虽然siRNA具有极好的效果和广泛的使用范围,但为了将siRNA开发为治疗剂,必须通过改善siRNA在体内的稳定性并增加细胞递送效率来将siRNA有效地递送至靶细胞(Harnessing in vivo siRNA delivery for drug discovery and therapeuticdevelopment.Drug Discov.Today.2006年1月;11(1-2):67-73)。
为了解决上述问题,正在对以下进行深入研究:对siRNA的一些核苷酸或骨架进行修饰以赋予其核酸酶抗性,以便改善其在体内的稳定性;以及载体如病毒载体、脂质体或纳米颗粒的使用。
使用病毒载体(如腺病毒或逆转录病毒)的递送系统具有高转染功效,但具有高免疫原性和致癌性。另一方面,含有纳米颗粒的非病毒递送系统的细胞递送效率低于病毒递送系统,但它是有利的,因为它在体内的高稳定性、靶标特异性递送的潜力、改善的递送效果(如所含有的RNAi寡核苷酸被摄取和内化至细胞或组织中)并且几乎无细胞毒性或免疫刺激,所以目前其被视为比病毒递送系统更强大的递送方法(Nonviral delivery ofsynthetic siRNAs in vivo.J Clin Invest.2007年12月3日;117(12):3623-3632)。
关于在非病毒递送系统中使用纳米载体的方法,使用各种聚合物(如脂质体、阳离子聚合物复合物等)形成纳米颗粒,并且将siRNA负载在这种纳米颗粒(即,纳米载体)上并且递送至细胞。在使用纳米载体的方法中,可主要使用聚合物纳米颗粒、聚合物胶束、阳离子脂质复合物(lipoplex)等,并且特别地,所述阳离子脂质复合物由阳离子脂质构成并且与细胞内体的阴离子脂质相互作用,导致使内体脱稳的效果,从而实现细胞内递送(Proc.Natl.Acad.Sci.15;93(21):11493-8,1996)。
为了改善siRNA的细胞内递送效率,已经使用siRNA缀合物开发了获得siRNA的稳定性和有效的细胞膜渗透性的技术,在所述缀合物中,作为生物相容性聚合物的亲水性物质(例如,聚乙二醇(PEG))通过简单的共价键或接头介导的共价键与siRNA缀合(韩国专利号883471)。然而,siRNA的化学修饰和聚乙二醇(PEG)的缀合(聚乙二醇化)仍具有缺点,如体内稳定性低和向靶器官递送的效率低。为了解决这些缺点,已经开发了双链寡核苷酸构建体,在所述构建体中亲水性物质和疏水性物质与寡核苷酸、特别是双链寡核苷酸(如siRNA)结合,并且所述构建体通过疏水性物质的疏水性相互作用形成自组装纳米颗粒,称为SAMiRNATM(自组装胶束抑制性RNA)(韩国专利号1224828)。与常规的递送技术相比,SAMiRNATM技术具有能够获得均匀的纳米颗粒同时大小非常小的优点。
关于SAMiRNATM技术的具体例子,将PEG(聚乙二醇)或HEG(六乙二醇)用作亲水性物质,并且PEG为合成聚合物且常用于增加药物(特别是蛋白质)的溶解度并控制药代动力学。PEG为多分散物质,并且一批聚合物由不同数目的单体的总和构成,且具有高斯分子量分布,并且物质的均匀性程度表示为多分散性指数(Mw/Mn)。特别地,当PEG具有低分子量(3-5kDa)时,其多分散性指数为约1.01,而高分子量(20kDa)的情况显示约1.2的高多分散性指数,因此分子量越高,物质的均匀性越低(F.M.Veronese.Peptide and proteinPEGylation:a review of problems and solutions.Biomaterials(2001)22:405-417)。因此,PEG与药物结合的情况是不利的,这是由于因为缀合物中反映出了PEG的多分散性特征,所以难以验证单一物质。因此,有通过改善PEG的合成和纯化过程来产生具有低多分散性指数的物质的趋势。特别地,在PEG与具有低分子量的物质结合的情况下,由于物质的多分散性特征而存在问题,如难以检查是否容易实现结合的不方便的要点(FrancescoM.Veronese和Gianfranco Pasut.PEGylation,successful approach to drugdelivery.DRUG DISCOVERY TODAY(2005)10(21):1451-1458)。
因此,近年来,作为现有的自组装纳米颗粒SAMiRNATM的改善形式,将组成SAMiRNATM的双链核苷酸构建体的亲水性物质封闭在基本单元中,所述基本单元包含1至15个具有一定分子量的均质单体和(必要时)接头,并且通过根据需要使用适当数目的嵌段,开发了递送载体技术的新形式,其大小小于现有SAMiRNATM并且具有显著改善的多分散性。
同时,据报道,到2024年,与脱发有关的全球市场将达到118亿美元(Grand ViewResearch,Inc)。七分之四的美国男性和五分之一的中国男性是秃头,并且在90%或更多的情况下,原因被认为是雄激素性脱发症。然而,迄今为止开发的大多数脱发预防药剂都靶向DHT和5-α-还原酶,并且尚未开发出靶向与雄激素直接有关的雄激素受体的药剂或头发生长产品。
因此,本发明人已作出大量努力来开发靶向与雄激素直接有关的雄激素受体的头发生长有关产品,并且确定了对雄激素受体具有特异性的某种序列可有效抑制雄激素受体的表达,并且包含其的双链寡核苷酸构建体和含有所述构建体的组合物在预防脱发或促进头发生长时非常有效,因此完成本发明。
发明内容
本发明的目的是提供:一种新型寡核苷酸序列,其对雄激素受体具有特异性并且能够以非常高的效率抑制其表达;以及一种双链寡核苷酸构建体,其用于将所述序列有效地递送至发根细胞。
本发明的另一个目标是提供一种纳米颗粒,所述纳米颗粒含有所述双链寡核苷酸构建体。
本发明的又另一个目的是提供一种用于预防脱发或促进头发生长的药物组合物,所述药物组合物含有所述新型寡核苷酸序列或所述双链寡核苷酸构建体作为活性成分。
本发明的又另一个目的是提供一种用于预防脱发或促进头发生长的化妆品组合物,所述化妆品组合物含有所述新型寡核苷酸序列或所述双链寡核苷酸构建体作为活性成分。
在实现上文和其他目的中,本发明提供了一种双链寡核苷酸构建体,所述双链寡核苷酸构建体具有下文结构式(1)的结构。
A-X-R-Y-B 结构式(1)
在结构式(1)中,A为亲水性物质,B为疏水性物质,X和Y中的每一个独立地表示简单的共价键或接头介导的共价键,并且R表示雄激素受体特异性寡核苷酸,所述雄激素受体特异性寡核苷酸包含含有选自SEQ ID NO:6、58、68、99、107、109、260、270、284、298、348、358、359和434的任一序列的有义链和含有与其互补的序列的反义链。
此外,本发明提供了一种纳米颗粒,所述纳米颗粒含有所述双链寡核苷酸构建体。
此外,本发明提供了一种用于预防脱发或促进头发生长的药物组合物,所述药物组合物含有所述双链寡核苷酸构建体或所述纳米颗粒作为活性成分。
此外,本发明提供了一种用于预防脱发或促进头发生长的化妆品组合物,所述化妆品组合物含有所述双链寡核苷酸构建体或所述纳米颗粒作为活性成分。
此外,本发明提供了一种治疗脱发的方法,所述方法包括向需要头发生长的受试者施用根据本发明的构建体、纳米颗粒或药物组合物,或向需要头发生长的区域上施加根据本发明的构建体、纳米颗粒或药物组合物。
此外,本发明提供了一种预防脱发或促进头发生长的方法,所述方法包括向需要预防脱发或头发生长的受试者或向相应区域上施用或施加根据本发明的构建体、纳米颗粒或化妆组合物。
此外,本发明提供了所述双链寡核苷酸构建体用于预防脱发或促进头发生长的用途。
此外,本发明提供了所述双链寡核苷酸构建体用于制造预防脱发或促进头发生长的药剂或化妆品的用途。
附图说明
图1显示了针对人雄激素受体特异性寡核苷酸候选序列设计的人雄激素受体mRNANM_000044.3(同种型1,10,661bp)和NM_001011645.2(同种型2,8112bp)的外显子图谱中的同种型共有区域;
图2显示了在针对人雄激素受体特异性寡核苷酸候选序列设计的同种型共有区域中使用2碱基滑动窗口算法选择由19个碱基构成的候选序列的过程;
图3显示了包含随机选择的雄激素受体特异性寡核苷酸的双链寡核苷酸的颗粒大小分布;
图4显示了544种类型的靶向雄激素受体的SAMiRNA的首次筛选结果;
图5显示了在图4中的筛选结果中针对14种具有最高雄激素受体表达抑制作用的序列选择包含雄激素受体特异性寡核苷酸的SAMiRNA的结果;
图6显示了对通过首次筛选所选择的包含雄激素受体特异性寡核苷酸的SAMiRNA进行二次筛选的结果;
图7显示了在对14种选择的序列和相关文献中已知的序列的SAMiRNA构建体进行处理之后,确认雄激素受体的蛋白质表达水平的结果;
图8显示了在对图7结果中的两种选择的序列和相关文献中的序列的SAMiRNA构建体进行处理之后,确认对蛋白质表达的抑制的结果;并且
图9显示了使用共聚焦激光扫描显微镜确认SAMiRNA纳米颗粒向发根细胞的递送效果的结果。
具体实施方式
除非另外定义,否则本文所用的所有技术和科学术语都具有与本发明所属领域的技术人员通常所理解的含义相同的含义。一般来讲,本文所用的命名和下文所述的测试方法均为本领域中熟知的且典型的。
在本发明中,为了选择能够靶向雄激素受体并抑制其表达的寡核苷酸,将2碱基滑动窗口算法应用于整个雄激素受体,从而确定候选序列列表。最终选择了与其他基因针对RNA序列具有15个或更少碱基的同一性的468种候选序列,并且使用总计544种寡核苷酸序列(包括已知相关文献(美国专利申请公开号US 2007-0141009)中披露的76种siRNA序列)测试了对雄激素受体的抑制程度,并且因此选择了14种特别有效的寡核苷酸。此外,所述寡核苷酸能够被制造成双链寡核苷酸构建体,因此增加细胞内递送效率,从而预防脱发并改善头发生长效果。
因此,本发明的一个方面涉及一种雄激素受体特异性双链寡核苷酸,所述雄激素受体特异性双链寡核苷酸包含含有选自SEQ ID NO:6、58、68、99、107、109、260、270、284、298、348、358、359和434的任一序列的有义链和含有与其互补的序列的反义链。
根据本发明的双链寡核苷酸是包括具有一般RNAi(RNA干扰)作用的所有物质的概念,并且如本发明所属领域中的普通技术人员所清楚的,所述雄激素受体特异性序列还包括雄激素受体特异性shRNA、ASO等。用于将siRNA递送至靶细胞中的常规方法仍是有问题的,这是由于siRNA穿过细胞膜被递送至细胞中且因此在它从细胞中的内体移动至细胞质时活性降低,并且还容易被体内存在的裂解酶降解。此外,其中将DNA(其为反义寡核苷酸)和用于降解靶mRNA的siRNA组合的DNA-RNA杂交体在体内比常规双链寡RNA稳定,并且其DNA部分具有能够与靶蛋白结合的适配体碱基序列,因此被有效地递送至靶细胞中,并且此外,所述DNA-RNA杂交体具有抑制RNA表达为蛋白质的siRNA碱基序列,所以其与靶细胞中的靶mRNA结合且抑制基因表达。此类DNA-RNA杂交体颗粒仅由生物物质构成,无毒且对体内存在的核酸酶DNA酶和RNA酶具有极大抗性,且因此可被视为RNAi的新技术。
此外,只要在包含选自SEQ ID NO:1至SEQ ID NO:468的任一序列的有义链或与其互补的反义链中维持对所述雄激素受体的特异性,本发明所属领域中的普通技术人员清楚的是,包含所述有义链(其包含其中至少一个碱基被取代、缺失或插入的序列)和所述反义链的雄激素受体特异性siRNA也被并入本发明的范围。
SEQ ID NO:1至468是人雄激素受体特异性序列,并且是与所述雄激素受体mRNA的其他位点具有15个或更少碱基序列的同源性的RNA有义链序列(表2)。此外,SEQ ID NO:469至544表示从现有专利(US 2007-0141009)已知的人雄激素受体特异性siRNA序列(表3)。
根据本发明,作为将细胞内活性与现有专利中披露的雄激素受体特异性寡核苷酸序列比较的结果,有可能发现效率优异并且与其他人mRNA的同源性较低的RNA序列。根据本发明的寡核苷酸优选地是包含选自SEQ ID NO:6、58、68、99、107、109、260、270、284、298、348、358、359和434的任一序列作为有义链的雄激素受体特异性寡核苷酸,并且更优选地是包含序列SEQ ID NO:68或109作为有义链的雄激素受体特异性寡核苷酸。
根据本发明的寡核苷酸的有义链和反义链优选地由19至31个核苷酸构成,并且含有选自SEQ ID NO:1至SEQ ID NO:468的任一序列的有义链以及与其互补的反义链被包含在内。
因为根据本发明的雄激素受体特异性寡核苷酸具有被设计成与编码所述相应基因的mRNA互补地结合的碱基序列,所以其特征在于,其能够有效抑制所述相应基因的表达。此外,其可包含突出端,所述突出端是在所述寡核苷酸的3'末端处包含一个、两个或更多个未配对核苷酸的结构。
此外,为了改善所述寡核苷酸在体内的稳定性,可以包含各种修饰,以赋予核酸酶抗性并减少非特异性免疫应答。在构成所述寡核苷酸的第一或第二寡核苷酸的修饰中,可组合使用至少一个选自以下的修饰:至少一个核苷酸中的糖结构的2'碳位置处的-OH基团被-CH3(甲基)、-OCH3(甲氧基)、-NH2、-F(氟)、-O-2-甲氧基乙基-O-丙基、-O-2-甲硫基乙基、-O-3-氨基丙基、-O-3-二甲基氨基丙基、-O-N-甲基乙酰胺基或-O-二甲基酰胺基氧基乙基取代的修饰;核苷酸中的糖结构中的氧被硫取代的修饰;以及核苷酸键至硫代磷酸酯、硼化磷酸酯或甲基膦酸酯键的修饰,并且还可以使用至PNA(肽核酸)、LNA(锁核酸)或UNA(非锁核酸)的修饰(Ann.Rev.Med.55,61-652004;US 5,660,985;US 5,958,691;US 6,531,584;US 5,808,023;US 6,326,358;US 6,175,001;Bioorg.Med.Chem.Lett.14:1139-1143,2003;RNA,9:1034-1048,2003;Nucleic Acid Res.31:589-595,2003;Nucleic AcidsResearch,38(17)5761-5773,2010;Nucleic Acids Research,39(5)1823-1832,2011)。
根据本发明的雄激素受体特异性寡核苷酸不仅抑制所述相应基因的表达,而且还显著抑制相应蛋白质的表达。
在一个替代性实施方案中,本发明提供了一种缀合物,在所述缀合物中亲水性物质和疏水性物质与双链寡核苷酸的两个末端缀合,以改善所述雄激素受体特异性双链寡核苷酸的体内稳定性和有效递送。
如上所述,亲水性物质和疏水性物质与双链寡核苷酸结合的双链寡核苷酸缀合物可以通过所述疏水性物质的疏水性相互作用形成自组装纳米颗粒(韩国专利号1224828)。此类纳米颗粒具有非常优异的体内递送效率和体内稳定性以及极好的颗粒大小均匀性的优点,所以质量控制容易并且制造药物的过程简单。
因此,本发明的另一个方面涉及一种双链寡核苷酸构建体,其具有以下结构式(1)的结构。
A-X-R-Y-B 结构式(1)
在结构式(1)中,A为亲水性物质,B为疏水性物质,X和Y中的每一个独立地表示简单的共价键或接头介导的共价键,并且R表示雄激素受体特异性寡核苷酸,所述雄激素受体特异性寡核苷酸包含含有选自SEQ ID NO:6、58、68、99、107、109、260、270、284、298、348、358、359和434的任一序列的有义链和含有与其互补的序列的反义链。
更优选地,根据本发明的包含雄激素受体特异性寡核苷酸的双链寡核苷酸构建体具有以下结构式(2)的结构。
在结构式(2)中,A、B、X和Y如结构式(1)中所定义,S表示所述雄激素受体特异性寡核苷酸的有义链,并且AS表示所述雄激素受体特异性寡核苷酸的反义链。
更优选地,包含所述雄激素受体特异性寡核苷酸的双链寡核苷酸构建体具有以下结构式(3)或(4)的结构。
在结构式(3)和结构式(4)中,A、B、S、AS、X和Y如结构式(1)中所定义,并且5'和3'表示所述雄激素受体特异性寡核苷酸的有义链的5'末端和3'末端。
以结构式(1)至结构式(4)的包含所述雄激素受体特异性寡核苷酸的双链寡核苷酸构建体可被配置成使得一个至三个磷酸酯基团与所述反义链的5'末端结合,并且可以使用shRNA代替RNA,如本发明所属领域中的普通技术人员所清楚的。
结构式(1)至结构式(4)中的亲水性物质优选地是分子量为200至10,000的聚合物物质,并且更优选地是分子量为1,000至2,000的聚合物物质。所述亲水性聚合物物质的例子优选地包括但不必限于非离子亲水性聚合物化合物,如聚乙二醇、聚乙烯吡咯烷酮、聚噁唑啉等。
特别地,结构式(1)至结构式(4)中的亲水性物质A可以以亲水性物质嵌段的形式使用,如以下结构式(5)或结构式(6)所表示。通过根据需要使用适当数目(结构式(5)或结构式(6)中的n)的此类亲水性物质嵌段,可以极大地缓和使用一般合成聚合物物质时可能发生的多分散性所致的问题。
(A'm-J)n 结构式(5)
(J-A'm)n 结构式(6)
在结构式(5)和结构式(6)中,A'为亲水性物质单体,J为用于将m个亲水性物质单体彼此连接或将m个亲水性物质单体和siRNA彼此连接的接头,m为1至15的整数,n为1至10的整数,并且由(A'm-J)或(J-A'm)表示的重复单元对应于亲水性物质嵌段的基本单元。
当使用如以结构式(5)或结构式(6)的亲水性物质嵌段时,根据本发明的包含所述雄激素受体特异性寡核苷酸的双链寡核苷酸构建体可具有以下结构式(7)或结构式(8)的结构。
(A'm-J)n-X-R-Y-B 结构式(7)
(J-A'm)n-X-R-Y-B 结构式(8)
在结构式(7)和结构式(8)中,X、R、Y和B如结构式(1)中所定义,并且A'、J、m和n如结构式(5)和结构式(6)中所定义。
在结构式(5)和结构式(6)中,在非离子亲水性聚合物的单体中,亲水性物质单体A'可无限制地使用,只要其满足本发明的目的即可,并且优选地是选自以下表1中所示的化合物(1)至化合物(3)的单体,并且更优选地是化合物(1)的单体。在化合物(1)中,G优选地选自CH2、O、S和NH。
特别地,在亲水性物质单体中,由化合物(1)表示的单体是有利的,因为可以向其中引入各种官能团,并且还因为其具有良好的体内亲和性和极好的生物相容性(如诱导较低的免疫应答),增加根据结构式(7)或结构式(8)的构建体中所含的寡核苷酸的体内稳定性并且增加其递送效率,所以其非常适合于制造根据本发明的构建体。
[表1]
本发明的亲水性物质单体的结构
对于结构式(5)至结构式(8)中的亲水性物质特别优选的是总分子量在1,000至2,000的范围内。因此,例如,当在结构式(7)和结构式(8)中使用根据化合物(1)的六乙二醇(即,G为O且m为6的物质)时,六乙二醇间隔基的分子量为344,所以重复数目n优选地是3至5。特别地,本发明的特征在于亲水性基团的重复单元(表示为结构式(5)和结构式(6)中的(A'm-J)或(J-A'm)n),即亲水性物质嵌段,可按需要使用适当数目(由n表示)。每个亲水性物质嵌段中包含的亲水性物质单体A和接头J在亲水性物质嵌段中可以独立地相同或不同。特别地,当使用三个亲水性物质嵌段(n=3)时,第一嵌段可包含根据化合物(1)的亲水性物质单体,第二嵌段可包含根据化合物(2)的亲水性物质单体,并且第三嵌段可包含根据化合物(3)的亲水性物质单体。以这种方式,不同的亲水性物质单体可用于所有亲水性物质嵌段,或者选自根据化合物(1)至化合物(3)的亲水性物质单体的任一亲水性物质单体可等同地用于所有亲水性物质嵌段。同样,介导亲水性物质单体的结合的接头也可针对每个亲水性物质嵌段使用相同接头或针对每个亲水性物质嵌段使用不同接头。此外,亲水性物质单体的数目m在亲水性物质嵌段中可以是相同或不同的。特别地,在第一亲水性物质嵌段中可连接三个亲水性物质单体(m=3),在第二亲水性物质嵌段中可连接五个亲水性物质单体(m=5),并且在第三亲水性物质嵌段中可连接四个亲水性物质单体(m=4)。以这种方式,在所有亲水性物质嵌段中可使用不同数目的亲水性物质单体,或者可使用相同数目的亲水性物质单体。
此外,在本发明中,所述接头J优选地选自PO3 -、SO3和CO2,但不限于此。可以使用任何接头,只要其满足根据所使用的亲水性物质的单体的本发明的目的即可,如本领域的普通技术人员清楚的。
结构式(1)至结构式(4)、结构式(7)和结构式(8)中的疏水性物质B在通过疏水性相互作用形成由根据结构式(1)至结构式(4)、结构式(7)和结构式(8)的寡核苷酸构建体构成的纳米颗粒方面起作用。所述疏水性物质的分子量优选地是250至1,000,并且其例子可包括但不限于类固醇衍生物、甘油酯衍生物、甘油醚、聚丙二醇、C12-C50不饱和或饱和烃、二酰基磷脂酰胆碱、脂肪酸、磷脂和脂多胺等,并且可使用任何疏水性物质,只要其满足本发明的目的即可,如本领域的普通技术人员清楚的。
类固醇衍生物可选自:胆固醇、胆甾烷醇、胆酸、胆甾醇基甲酸酯、胆甾烷基甲酸酯和胆甾醇胺,并且甘油酯衍生物可选自甘油单酯、甘油二酯和甘油三酯。在此,甘油酯的脂肪酸优选地是C12-C50不饱和或饱和脂肪酸。
特别地,在所述疏水性物质中,饱和或不饱和烃或胆固醇是优选的,这是由于其具有能够在根据本发明的寡核苷酸构建体的合成步骤中容易地结合的优点,并且C24烃、特别是含有二硫键的形式是最优选的。
所述疏水性物质结合至亲水性物质的远端,并且可结合至所述寡核苷酸的有义链或反义链上的任何位置。
根据本发明的结构式(1)至结构式(4)、结构式(7)和结构式(8)中的亲水性物质或疏水性物质和雄激素受体特异性核苷酸经由简单的共价键或接头介导的共价键(X或Y)结合在一起。介导所述共价键的接头在所述亲水性物质或疏水性物质和所述雄激素受体特异性寡核苷酸的末端共价接合,并且没有特别的限制,只要其必要时在特定环境中提供可裂解键即可。因此,所述接头可以是在制造根据本发明的双链寡核苷酸构建体的过程期间接合以激活所述雄激素受体特异性寡核苷酸和/或所述亲水性物质(或疏水性物质)的任何化合物。所述共价键可以是不可裂解键或可裂解键。在此,所述不可裂解键可以是酰胺键或磷酸酯键,并且所述可裂解键可以是二硫键、酸可裂解键、酯键、酸酐键、生物可降解键或酶可裂解键,但本发明不限于此。
此外,结构式(1)至结构式(4)、结构式(7)和结构式(8)中由R(或S和AS)表示的雄激素受体特异性寡核苷酸可无限制地使用,只要其是能够与所述雄激素受体的mRNA特异性结合的序列即可。在本发明中,所述雄激素受体特异性寡核苷酸优选地由包含选自SEQ IDNO:6、58、68、99、107、109、260、270、284、298、348、358、359和434的任一序列的有义链和包含与其互补的序列的反义链构成。
特别地,根据本发明的结构式(1)至结构式(4)、结构式(7)和结构式(8)中所含的siRNA优选地是由包含选自SEQ ID NO:6、58、68、99、107、109、260、270、284、298、348、358、359和434的任一序列的有义链和包含与其互补的序列的反义链构成的雄激素受体特异性寡核苷酸。
在根据本发明的包含雄激素受体特异性寡核苷酸的双链寡核苷酸构建体中,可在与所述寡核苷酸结合的末端部分相对的亲水性物质末端部分处另外引入胺基团或多组氨酸基团。
这用于促进根据本发明的包含雄激素受体特异性寡核苷酸的双链寡核苷酸构建体的载体的细胞内引入及其从内体的逃逸。为了促进所述载体(如量子点、树枝状大分子、脂质体等)的细胞内引入及其从内体的逃逸,已报道了胺基团和多组氨酸基团的使用及其效果。
特别地,在所述载体末端或外部修饰的伯胺基团通过静电相互作用与带负电荷的基因形成缀合物,同时在体内pH下质子化,并且在其引入细胞内之后,可以保护所述载体免于溶酶体的降解,因为由于内部叔胺在内体的低pH下具有缓冲作用而促进了从内体的逃逸(Gene transfer and expression inhibition using polymer-based hybridmaterials.Polymer Sci.Technol.,第23卷,第3期,第254-259页)。此外,组氨酸作为非必需氨基酸在残基(-R)处具有咪唑啉(pKa3 6.04),从而有效增加内体和溶酶体的缓冲能力,因此已知的是,组氨酸修饰可用于增加包括脂质体在内的非病毒基因载体中的内体逃逸效率(Novel histidine-conjugated galactosylated cationic liposomes for efficienthepatocyte selective gene transfer in human hepatoma HepG2 cells.J.ControlledRelease 118,第262-270页)。
胺基团或多组氨酸基团可经由至少一个接头与亲水性物质或亲水性物质嵌段连接。
当将胺基团或多组氨酸基团引入根据本发明的结构式(1)的双链寡核苷酸构建体的亲水性物质中时,可以表示为结构式(9)的结构。
P-J1-J2-A-X-R-Y-B结构式(9)
在结构式(9)中,A、B、R、X和Y如结构式(1)中所定义。
P表示胺基团或多组氨酸基团,J1和J2为接头,J1和J2可独立地选自简单的共价键、PO3 -、SO3、CO2、C2-12烷基、烯基和炔基,但不限于此,并且根据所使用的亲水性物质的类型,可使用J1和J2的任何接头,只要其满足本发明的目的即可,如本领域的普通技术人员清楚的。
当引入胺基团时,J2优选地是简单的共价键或PO3 -,并且J1优选地是C6烷基,但本发明不限于此。
另外,当引入多组氨酸基团时,在结构式(9)中,J2优选地是简单的共价键或PO3 -,并且J1优选地是以下化合物(4),但本发明不限于此。
此外,当根据结构式(9)的双链寡核苷酸构建体的亲水性物质是根据结构式(5)或结构式(6)的亲水性物质嵌段时,并且还当将胺基团或多组氨酸基团被引入其中时,可表示为结构式(10)或结构式(11)的结构。
P-J1-J2-(A'm-J)n-X-R-Y-B 结构式(10)
P-J1-J2-(J-A'm)n-X-R-Y-B 结构式(11)
在结构式(10)和结构式(11)中,X、R、Y、B、A'、J、m和n如结构式(5)或结构式(6)中所定义,并且P、J1和J2如结构式(9)中所定义。
特别地,在结构式(10)和结构式(11)中,所述亲水性物质优选地以结合至所述雄激素受体特异性寡核苷酸有义链的3'末端的形式提供。在此,结构式(9)至结构式(11)可具有以下结构式(12)至结构式(14)的形式。
在结构式(12)至结构式(14)中,X、R、Y、B、A、A'、J、m、n、P、J1和J2如结构式(9)至结构式(11)中所定义,并且5'和3'表示所述雄激素受体特异性寡核苷酸的有义链的5'末端和3'末端。
作为可在本发明中引入的胺基团,可使用伯胺基团至叔胺基团,并且使用伯胺基团是特别优选的。所引入的胺基团可以以胺盐的形式提供,并且例如,伯胺基团的盐可以以NH3 +的形式提供。
另外,可在本发明中引入的多组氨酸基团优选地包含3至10个组氨酸,特别优选5至8个组氨酸,并且最优选6个组氨酸。此外,除组氨酸之外,还可包含至少一个半胱氨酸。
同时,当根据本发明的包含雄激素受体特异性寡核苷酸的双链寡核苷酸构建体和由其形成的纳米颗粒与靶向部分一起提供时,其向靶细胞中的递送被有效地促进,并且因此其可以甚至以相对低的剂量递送至靶细胞以展现出高靶基因表达调节功能,并能够阻止非特异性雄激素受体特异性寡核苷酸向其他器官和细胞的递送。
因此,本发明提供了一种双链寡核苷酸构建体,其被配置成使得配体L、特别是具有与通过受体介导的内吞作用(RME)促进靶细胞内化的受体特异性结合的特性的配体另外地与根据结构式(1)至结构式(4)、结构式(7)和结构式(8)的构建体结合。例如,其中所述配体与根据结构式(1)的双链寡核苷酸构建体结合的形式具有以下结构式(15)的结构。
(Li-Z)-A-X-R-Y-B 结构式(15)
在结构式(15)中,A、B、X和Y如结构式(1)中所定义,L为具有与通过受体介导的内吞作用(RME)促进靶细胞内化的受体特异性结合的特性的配体,并且i为1至5的整数,优选1至3的整数。
结构式(15)中的配体优选地选自:具有能够以靶细胞特异性方式促进细胞内化的RME特性的靶受体特异性抗体、适配体和肽;以及化学物质,包括叶酸(术语叶酸(folate)和叶酸(folic acid)通常可彼此互换使用,其中如本文中所使用的“叶酸”(“folate”)意指在人体内处于自然状态或激活状态的叶酸(folate))、己糖胺(hexoamine)(如N-乙酰基半乳糖胺(NAG))、糖或碳水化合物(如葡萄糖或甘露糖)等,但不限于此。
此外,结构式(15)中的亲水性物质A可以以根据结构式(5)和结构式(6)的亲水性物质嵌段的形式使用。
本发明的另一个方面涉及一种纳米颗粒,其包含含有所述雄激素受体特异性寡核苷酸的双链寡核苷酸构建体。
如上所述,包含所述雄激素受体特异性寡核苷酸的双链寡核苷酸构建体是两亲性的,因为其中包含疏水性物质和亲水性物质两者,并且所述亲水性部分具有通过与体内存在的水分子的相互作用(如氢键等)而具有亲和力且因此向外定向,并且所述疏水性物质通过它们之间的疏水性相互作用而向内定向,因此形成热力学稳定的纳米颗粒。特别地,所述疏水性物质位于所述纳米颗粒的中心,并且所述亲水性物质位于所述雄激素受体特异性寡核苷酸的外部方向,从而得到具有保护所述雄激素受体特异性寡核苷酸的形式的纳米颗粒。因此所形成的纳米颗粒改善所述雄激素受体特异性寡核苷酸的细胞内递送且增加寡核苷酸功效。
根据本发明的纳米颗粒可仅用包含具有相同序列的寡核苷酸的双链寡核苷酸构建体形成,或者也可由包含具有不同序列的寡核苷酸的双链寡核苷酸构建体构成。在本发明中,具有不同序列的寡核苷酸可以是对作为不同靶基因的雄激素受体具有特异性的寡核苷酸,并且可以并入不同序列但具有相同靶基因特异性的情况。
另外,除所述雄激素受体特异性寡核苷酸之外,包含对其他脱发相关基因具有特异性的siRNA的双链寡核苷酸构建体也可包括在根据本发明的纳米颗粒的范围内。
本发明的另一个方面涉及一种用于预防脱发、特别是雄激素性脱发症,或促进头发生长的药物组合物,所述药物组合物含有雄激素受体特异性双链寡核苷酸、包含其的双链寡核苷酸构建体和/或包含所述双链寡核苷酸构建体的纳米颗粒作为活性成分。
所述药物组合物可用于选自膏剂、糊剂、凝胶、冻胶、血清、气溶胶喷雾剂、非气溶胶喷雾剂、泡沫、霜剂、洗剂、溶液和混悬液配制品的配制品,但不限于此。
根据本发明的组合物通过抑制睾酮的代谢物DHT与雄激素受体的结合来展现出预防脱发或与诱导头发生长的作用。
除根据本发明的双链寡核苷酸或其构建体之外,根据本发明的组合物中还可包含对除雄激素受体之外的脱发疾病相关基因具有特异性的双链寡核苷酸或包含其的双链寡核苷酸构建体。
根据本发明的组合物可应用于与参与所述雄激素受体的上游或下游信号传导的基因相关的脱发、特别是雄激素性脱发症,但不限于此。
本发明的组合物可被制造成除上述活性成分之外,还包含至少一种药学上可接受的载体。所述药学上可接受的载体必须与本发明的活性成分相容,并且可包括盐水、无菌水、林格氏溶液、缓冲盐水、右旋糖溶液、麦芽糖糊精溶液、甘油和乙醇,其可单独使用或以其两种或更多种的组合的形式使用。另外,可按需要添加其他典型添加剂,如抗氧化剂、缓冲液、抑菌剂等。另外,可进一步添加稀释剂、分散剂、表面活性剂、粘合剂和润滑剂,以制造可注射配制品,如水溶液、混悬液、乳液等。特别地,优选提供以冻干形式的配制品。为了制造冻干配制品,可使用本发明所属领域中通常已知的方法,并且可添加用于冻干的稳定剂。此外,优选根据每种疾病或组分使用本领域中的适当方法或使用Remington'sPharmaceutical Science(Mack Publishing Company,Easton PA)中所披露的方法来制造配制品。
本发明的组合物中所包含的活性成分等的量和施用方法可由本领域的普通技术专家基于个体脱发的症状和严重性来确定。此外,本发明的组合物可以以各种形式配制,如粉末、片剂、注射剂、膏剂等,且可提供在单位剂量或多剂量容器(如密封安瓿和瓶)中。
本发明的另一个方面提供了一种用于预防脱发、特别是雄激素性脱发症,或促进头发生长的化妆品组合物,所述化妆品组合物含有雄激素受体特异性双链寡核苷酸、包含其的双链寡核苷酸构建体和/或包含所述双链寡核苷酸构建体的纳米颗粒作为活性成分。
所述组合物可用于选自以下的配制品:生发液、头发调理剂、头发精华、头发洗剂、头发营养洗剂、洗发香波、护发素、头发处理剂、发膏、营养发膏、保湿发膏、按摩发膏、发蜡、发用气溶胶、发膜、营养发膜、洗发皂、头发清洁泡沫、发油、干发剂、头发保护剂、染发剂、卷发剂、头发脱色剂、发胶、发釉、头发敷料、粘发剂、头发保湿剂、发用摩丝和喷发配制品,但不限于此。
本发明的另一个方面提供了一种治疗脱发的方法,其包括向需要头发生长的受试者施用根据本发明的构建体、纳米颗粒或药物组合物,或向需要头发生长的区域上施加根据本发明的构建体、纳米颗粒或药物组合物。
此外,本发明涉及一种预防脱发或促进头发生长的方法,其包括向需要预防脱发或头发生长的受试者或向相应区域上施用或施加根据本发明的构建体、纳米颗粒或化妆品组合物。
此外,本发明涉及所述双链寡核苷酸构建体用于预防脱发或促进头发生长的用途。
此外,本发明涉及所述双链寡核苷酸构建体用于制造预防脱发或促进头发生长的药剂或化妆品的用途。
本发明中的脱发包括雄激素性脱发症、斑秃和休止期落发。
通过以下实施例可以更好地理解本发明。这些实施例仅用于说明本发明,且不应解释为限制本发明的范围,如对于本领域的普通技术人员而言清楚的。
实施例1.靶向雄激素受体的寡核苷酸筛选的算法和候选序列选择
基于siRNA的高通量药物筛选方法能够通过将1碱基或2碱基滑动窗口算法应用于总mRNA来生成所有可能的候选序列,并且还能够通过同源性过滤去除不必要的候选序列,从而确认所有最终选择的寡核苷酸的基因表达的抑制程度。
首先,以基于人雄激素受体mRNA NM_000044.3(同种型1,10,661bp)和NM_001011645.2(同种型2,8112bp)的外显子图谱提取同种型共有区域的方式进行针对雄激素受体的寡核苷酸候选序列的设计过程,并且将2碱基滑动窗口算法应用于提取的同种型共有区域,从而选择3,956种由19个碱基构成的候选序列。
在选择的寡核苷酸候选序列列表中,当人总参考序列RNA的BLAST e值为100或更小时,最终选择与其他基因针对RNA序列具有15个或更少碱基的同一性的468种候选序列。在此,使用总计544种寡核苷酸序列(包括先前已知的相关文献(美国专利申请公布号US2007-0141009)中提及的76种siRNA序列)进行关于雄激素受体表达的抑制程度的实验。
[表2]
通过2碱基滑动窗口筛选所选择的雄激素受体特异性寡核苷酸候选序列
[表3]
相关文献(US 2007-0141009A)中所述的雄激素受体特异性siRNA序列
实施例2.双链寡核苷酸构建体的合成
本发明中制造的双链寡核苷酸构建体(SAMiRNA)具有由以下结构式表示的结构。
合成过程包括在核苷所附接的固体支持物(CPG)上重复包括去封闭、偶联、加帽和氧化的循环,从而获得具有所需序列的RNA单链。将RNA合成仪(384合成仪,BIONEER,韩国)用于双链寡RNA的一系列合成过程。
双链寡核苷酸构建体的有义链是通过以下方式来制造:在作为支持物的聚乙二醇(PEG)-CPG上使用β-氰基乙基亚磷酰胺连接构成DNA骨架的磷酸二酯键,以合成具有含有结合至3'末端的聚乙二醇的有义链和亲水性物质的双链寡核苷酸构建体,然后将含有二硫键的C24结合至5'末端。对于待与有义链一起退火的反义链,具有与有义链互补的序列的反义链是通过以下方式来制造:使用β-氰基乙基亚磷酰胺连接构成RNA骨架的磷酸二酯键,然后使用用于将磷酸酯基团连接至5'末端的化学磷酸化试剂(CPR)制造具有结合至5'末端的磷酸酯基团的反义链。
合成完成之后,在60℃的水浴中使用28%(v/v)氨,将合成的寡核苷酸单链和寡核苷酸-聚合物构建体与CPG分离,接着进行脱保护以去除保护性残基。在70℃的烘箱中,用体积比为10:3:4的N-甲基吡咯烷酮、三乙胺和三乙胺三氢氟酸盐处理脱保护的寡核苷酸单链和寡核苷酸-聚合物构建体,从而去除2'。通过高效液相色谱法(HPLC)从反应混合物中分离出寡核苷酸单链、寡核苷酸-聚合物构建体和配体结合的寡核苷酸-聚合物构建体,并且使用MALDI-TOF质谱仪(SHIMADZU,Japan)测量其分子量,并且确认所得产物是否与待合成的碱基序列和寡核苷酸-聚合物构建体匹配。然后,为了制造每个双链寡核苷酸构建体,将有义链和反义链以相同量混合并放置于pH为7.0或更大的1X退火缓冲液(30mM HEPES、100mM乙酸钾和2mM乙酸镁)中,使其在90℃的恒温水浴中反应3分钟,然后使其在37℃下再次反应,从而制造所需的SAMiRNA、monoSAMiRNA(n=1)、monoSAMiRNA(n=2)、monoSAMiRNA(n=3)和monoSAMiRNA(n=4)。通过电泳确认由此制造的双链寡核苷酸构建体的退火。
实施例3.通过靶向雄激素受体筛选诱导RNAi的SAMiRNA纳米颗粒
3.1SAMiRNA纳米颗粒的制造和颗粒大小分析
基于使用Zetasizer Nano ZS(Malvern,英国)针对实施例2中合成的544种类型的靶向雄激素受体序列的SAMiRNA进行的颗粒大小分析所得的SAMiRNA的大小和多分散性指数的测量结果,随机选择的SAMiRNA的纳米颗粒的大小和多分散性指数示于以下表4中,并且其代表性图示于图3中。
[表4]
雄激素受体特异性SAMiRNA的纳米颗粒大小和多分散性指数
SEQ ID NO: | 代码名称 | 大小 | PDI |
545 | SAMi-对照 | 28±1.0 | 0.28±0.04 |
10 | SAMi-AR#10 | 27.8±0.7 | 0.18±0.07 |
3.2SAMiRNA纳米颗粒的细胞内处理方法
使用人源性前列腺癌细胞系LNCaP来发现抑制雄激素受体的表达的SAMiRNA,并且在37℃和5%CO2下使用含有10%胎牛血清(HyClone,美国)和1%青霉素-链霉素(HyClone,美国)的RPMI培养基(HyClone,美国)培养LNCaP细胞系。使用与上文相同的培养基,将LNCaP细胞系以4×104个细胞/孔分配在12孔板(Costar,美国)上,并且在第二天,用1X DPBS稀释SAMiRNA并以50nM用于处理细胞。在所述处理条件下处理SAMiRNA,每12小时一次,总计4次,且在37℃和5%CO2下培养。
3.3通过分析抑制雄激素受体mRNA表达的功效进行SAMiRNA筛选
使用具有寡聚(dT)20的RocketScriptTM Cycle RT Premix将从如实施例3.2中的SAMiRNA处理的细胞提取出的RNA合成为cDNA,然后使用Taqman探针型多重qPCR方法分析与SAMiRNA对照样品相比,雄激素受体基因的相对表达水平。
因此,如图4所示,从544种靶向雄激素受体的SAMiRNA(图5)中的展示抑制雄激素受体mRNA的表达60%或更多的序列中选择出9种在相关专利(US 2007-0141009A)中提及的序列和14种表2中的序列,并且对14种序列抑制雄激素受体mRNA表达的能力的再评估示于图6中。最终选择了两种最有效抑制雄激素受体基因表达的SAMiRNA,并且相应SAMiRNA的序列信息示于以下表5中。
[表5]
有效抑制雄激素受体表达的SAMiRNA序列
SEQ ID NO: | 代码名称 | 位置 | 有义链序列 |
68 | SAMi-AR#68 | 3495-3513 | GAGTTTGGATGGCTCCAAA |
109 | SAMi-AR#109 | 3991-4009 | ATGTACAGTCTGTCATGAA |
3.4选择的SAMiRNA抑制雄激素受体蛋白质表达的功效评价
进行蛋白质印记(WB)测定以确认包括实施例3.3中选择的第68和109号序列在内的共同选择的14种SAMiRNA是否有效抑制雄激素受体蛋白质表达。将LNCaP细胞系以1.2×105个细胞/孔分配到6孔板(Costar,美国)中,并在37℃和5%CO2下培养。第二天,使用lipofectamine(Invitrogen,美国)以50nM的浓度进行转染。培养48小时后,取出培养基并使用含有蛋白酶抑制剂混合物(Sigma Aldrich,美国)的细胞裂解缓冲液(Cell SignalingTechnology,美国)分离出蛋白质。在使用BCA测定试剂盒(Thermo,美国)定量蛋白质的量后,将20μg蛋白质与Laemmli 5x样品缓冲液一起在95℃下煮沸10分钟。将变性的蛋白质在SDS-聚丙烯酰胺凝胶上电泳,然后转移至PVDF膜上。将膜浸入封闭溶液(5%在TBS中的脱脂奶粉和0.05%Tween 20)并且在室温下处理1小时,接着在4℃冰箱中与一抗AR抗体(1:2000,Santa Cruz,美国)和GAPDH抗体(1:5000,Cell Signaling Technology,美国)反应过夜,用TBST洗涤三次,然后在室温下与辣根过氧化物酶缀合的二抗(Cell SignalingTechnology)反应1小时,然后使用Pico化学发光底物(Thermo,美国)作为化学发光试剂检测蛋白质条带。
如图7所示确认14种类型的SAMiRNA抑制雄激素受体蛋白质表达的能力,并且第68和109号序列在蛋白质表达方面的抑制能力也非常优异。
3.5在作为人源性发根细胞的毛囊真皮乳头细胞(HFDPC)中抑制雄激素受体蛋白质表达的功效评价
为了确认实施例3.4中最终选择的SEQ ID NO:68和109是否真的在人发根细胞中抑制雄激素受体蛋白质表达,使用人源性发根细胞(即毛囊真皮乳头细胞(HFDPC))测量了蛋白质表达的抑制程度(图8)。发现两种序列均能够抑制雄激素受体蛋白表达。
实施例4.SAMiRNA纳米颗粒的真皮内递送效果的确认
为了确认用最终选择的SEQ ID NO:68和109制造的SAMiRNA-AR#68和SAMiRNA-AR#109是否真的递送至人发根,测量了人发中基因转移的效果。
在实验当天通过揪发尖来收集头发,剪至离根部约1cm的长度,并在培养箱中使用200μl M199培养基(10%FBS+1%青霉素)在96孔板中培养1小时。然后,为了观察基因转移,在培养箱中使用200μl含有2μM和10μM用荧光物质(FAM染料)标记的SAMiRNA的M199培养基培养24小时。物质处理24小时后,使用DPBS洗涤三次,且最终,在含有3.7%甲醛和2%FBS的PBS中将发根固定20分钟。
将已固定的发根种植在含有OCT化合物的基底模具中并放置在预冷冻的不锈钢板上以将OCT化合物完全冷冻。将冷冻的组织在-70℃下储存并在-20℃下静置约30分钟以有利于组织切片,然后用组织切片机进行切割。将切片的组织放置在10μm厚的载玻片上并干燥1小时,并且在干燥后进行封固过程。在此,使用含有DAPI的封固介质。基于使用共聚焦激光扫描显微镜(LSM5 LIVE CONFIGURATION VARIOTWO VRGB)观察荧光的结果,确认了SAMiRNA被递送至头发组织的发根细胞(图9)。
尽管已如上所述详细公开了本发明的具体实施方案,但对于本领域中的技术人员清楚的是,描述仅为优选的示例性实施方案且不应解释为限制本发明的范围。因此,本发明的实质范围将由所附权利要求书及其等同物定义。
工业实用性
根据本发明,包含雄激素受体特异性寡核苷酸的双链寡核苷酸构建体和包含其作为活性成分的用于预防脱发或促进头发生长的组合物可高效地抑制雄激素受体的表达而无副作用,且可因此对预防脱发(特别是雄激素性脱发症、斑秃和休止期落发)和促进头发生长展现出极好的效果。
序列表文本文件
附有电子文件。
序列表
<110> 柏业公司
<120> 包含雄激素受体特异性序列的双链寡核苷酸构建体以及包含其的用于预防脱发和促进头发生长的组合物
<130> PF-B2620
<140> PCT/KR2019/015723
<141> 2019-11-18
<150> 10-2018-0149562
<151> 2018-11-28
<160> 545
<170> PatentIn version 3.5
<210> 1
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 1
acugccaggg accauguuu 19
<210> 2
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 2
ugccagggac cauguuuug 19
<210> 3
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 3
ccagggacca uguuuugcc 19
<210> 4
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 4
agggaccaug uuuugccca 19
<210> 5
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 5
uuuugcccau ugacuauua 19
<210> 6
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 6
uugcccauug acuauuacu 19
<210> 7
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 7
auugacuauu acuuuccac 19
<210> 8
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 8
ugacuauuac uuuccaccc 19
<210> 9
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 9
acuauuacuu uccacccca 19
<210> 10
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 10
uauuacuuuc caccccaga 19
<210> 11
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 11
agaagaccug ccugaucug 19
<210> 12
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 12
cuucuucaaa agagccgcu 19
<210> 13
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 13
cacuauugau aaauuccga 19
<210> 14
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 14
cuauugauaa auuccgaag 19
<210> 15
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 15
auuguccauc uugucgucu 19
<210> 16
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 16
gucgucuucg gaaauguua 19
<210> 17
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 17
uucggaaaug uuaugaagc 19
<210> 18
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 18
aauguuauga agcagggau 19
<210> 19
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 19
cugacagugu cacacauug 19
<210> 20
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 20
gaaggcuaug aaugucagc 19
<210> 21
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 21
uagugugugc uggacacga 19
<210> 22
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 22
gugugugcug gacacgaca 19
<210> 23
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 23
aacaaccagc ccgacuccu 19
<210> 24
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 24
gcccgacucc uuugcagcc 19
<210> 25
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 25
ugcucucuag ccucaauga 19
<210> 26
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 26
gagagacagc uuguacacg 19
<210> 27
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 27
gcuuguacac guggucaag 19
<210> 28
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 28
uuguacacgu ggucaagug 19
<210> 29
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 29
guacacgugg ucaaguggg 19
<210> 30
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 30
acacgugguc aagugggcc 19
<210> 31
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 31
acguggucaa gugggccaa 19
<210> 32
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 32
ggucaagugg gccaaggcc 19
<210> 33
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 33
ccuggcuucc gcaacuuac 19
<210> 34
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 34
uggcuuccgc aacuuacac 19
<210> 35
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 35
gcuuccgcaa cuuacacgu 19
<210> 36
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 36
uuccgcaacu uacacgugg 19
<210> 37
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 37
ccgcaacuua cacguggac 19
<210> 38
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 38
gcaacuuaca cguggacga 19
<210> 39
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 39
cacguggacg accagaugg 19
<210> 40
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 40
gacgaccaga uggcuguca 19
<210> 41
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 41
ucauucagua cuccuggau 19
<210> 42
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 42
gcucauggug uuugccaug 19
<210> 43
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 43
ccaugggcug gcgauccuu 19
<210> 44
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 44
uggcgauccu ucaccaaug 19
<210> 45
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 45
augucaacuc caggaugcu 19
<210> 46
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 46
acuccaggau gcucuacuu 19
<210> 47
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 47
caggaugcuc uacuucgcc 19
<210> 48
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 48
ggaugcucua cuucgcccc 19
<210> 49
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 49
augcucuacu ucgccccug 19
<210> 50
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 50
gcucuacuuc gccccugau 19
<210> 51
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 51
ucuacuucgc cccugaucu 19
<210> 52
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 52
uacuucgccc cugaucugg 19
<210> 53
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 53
cuucgccccu gaucugguu 19
<210> 54
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 54
ucgccccuga ucugguuuu 19
<210> 55
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 55
gccccugauc ugguuuuca 19
<210> 56
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 56
cccugaucug guuuucaau 19
<210> 57
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 57
ucaaugagua ccgcaugca 19
<210> 58
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 58
aaugaguacc gcaugcaca 19
<210> 59
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 59
uaccgcaugc acaaguccc 19
<210> 60
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 60
ccgcaugcac aagucccgg 19
<210> 61
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 61
gcaugcacaa gucccggau 19
<210> 62
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 62
cccggaugua cagccagug 19
<210> 63
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 63
cagccagugu guccgaaug 19
<210> 64
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 64
gccagugugu ccgaaugag 19
<210> 65
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 65
cagugugucc gaaugaggc 19
<210> 66
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 66
guguccgaau gaggcaccu 19
<210> 67
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 67
gaggcaccuc ucucaagag 19
<210> 68
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 68
gaguuuggau ggcuccaaa 19
<210> 69
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 69
cuccaaauca ccccccagg 19
<210> 70
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 70
ccaaaucacc ccccaggaa 19
<210> 71
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 71
auuccugugc augaaagca 19
<210> 72
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 72
ccaguggaug ggcugaaaa 19
<210> 73
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 73
aguggauggg cugaaaaau 19
<210> 74
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 74
augaacuucg aaugaacua 19
<210> 75
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 75
gaacuucgaa ugaacuaca 19
<210> 76
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 76
acuucgaaug aacuacauc 19
<210> 77
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 77
uucgaaugaa cuacaucaa 19
<210> 78
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 78
cgaaugaacu acaucaagg 19
<210> 79
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 79
aucaaggaac ucgaucgua 19
<210> 80
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 80
caaggaacuc gaucguauc 19
<210> 81
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 81
aggaacucga ucguaucau 19
<210> 82
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 82
gaacucgauc guaucauug 19
<210> 83
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 83
acucgaucgu aucauugca 19
<210> 84
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 84
ucgaucguau cauugcaug 19
<210> 85
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 85
gaucguauca uugcaugca 19
<210> 86
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 86
uccugcucaa gacgcuucu 19
<210> 87
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 87
cugcucaaga cgcuucuac 19
<210> 88
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 88
acuccgugca gccuauugc 19
<210> 89
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 89
uccgugcagc cuauugcga 19
<210> 90
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 90
cgugcagccu auugcgaga 19
<210> 91
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 91
ugcagccuau ugcgagaga 19
<210> 92
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 92
cagccuauug cgagagagc 19
<210> 93
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 93
gccuauugcg agagagcug 19
<210> 94
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 94
uuuugaccug cuaaucaag 19
<210> 95
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 95
cuaaucaagu cacacaugg 19
<210> 96
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 96
aagucacaca uggugagcg 19
<210> 97
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 97
gcguggacuu uccggaaau 19
<210> 98
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 98
uuuccggaaa ugauggcag 19
<210> 99
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 99
gaaagucaag cccaucuau 19
<210> 100
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 100
aagucaagcc caucuauuu 19
<210> 101
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 101
cuguuauaac ucugcacua 19
<210> 102
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 102
guuauaacuc ugcacuacu 19
<210> 103
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 103
uauaacucug cacuacucc 19
<210> 104
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 104
ucugcacuac uccucugca 19
<210> 105
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 105
uuggggaauu uccucuauu 19
<210> 106
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 106
ggggaauuuc cucuauuga 19
<210> 107
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 107
auugauguac agucuguca 19
<210> 108
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 108
ugauguacag ucugucaug 19
<210> 109
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 109
auguacaguc ugucaugaa 19
<210> 110
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 110
guacagucug ucaugaaca 19
<210> 111
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 111
auucuauuug cugggcuuu 19
<210> 112
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 112
uucccucccu aucuaaccc 19
<210> 113
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 113
cccucccuau cuaacccuc 19
<210> 114
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 114
cucccuaucu aacccuccc 19
<210> 115
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 115
cccuaucuaa cccucccau 19
<210> 116
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 116
cuaucuaacc cucccaugg 19
<210> 117
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 117
cucccauggc accuucaga 19
<210> 118
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 118
cccauggcac cuucagacu 19
<210> 119
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 119
ccauuguggc uccuaucug 19
<210> 120
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 120
auuguggcuc cuaucugug 19
<210> 121
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 121
gcuccuaucu guguuuuga 19
<210> 122
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 122
cauauggccc agugucaag 19
<210> 123
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 123
uauggcccag ugucaaguu 19
<210> 124
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 124
uguuuacagc acuacucug 19
<210> 125
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 125
gccacacaaa cguuuacuu 19
<210> 126
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 126
uacuuaucuu augccacgg 19
<210> 127
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 127
cuuaucuuau gccacggga 19
<210> 128
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 128
augccacggg aaguuuaga 19
<210> 129
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 129
aaguuuagag agcuaagau 19
<210> 130
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 130
guuuagagag cuaagauua 19
<210> 131
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 131
uuagagagcu aagauuauc 19
<210> 132
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 132
agagagcuaa gauuaucug 19
<210> 133
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 133
gaggccaaua gugacgaga 19
<210> 134
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 134
gugacgagaa ggugaaaau 19
<210> 135
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 135
gacgagaagg ugaaaauug 19
<210> 136
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 136
ccauggggag uuacugauu 19
<210> 137
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 137
uccacgggag acuuuauuu 19
<210> 138
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 138
cacgggagac uuuauuuuc 19
<210> 139
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 139
ggcuauugcc auuagaggg 19
<210> 140
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 140
cuauugccau uagagggca 19
<210> 141
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 141
aaggagggca auggagcau 19
<210> 142
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 142
ggagggcaau ggagcauca 19
<210> 143
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 143
agggcaaugg agcaucagu 19
<210> 144
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 144
ggcaauggag caucaguac 19
<210> 145
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 145
aguaccugcc cacagccuu 19
<210> 146
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 146
gucccugggg gcuagacug 19
<210> 147
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 147
gggggcuaga cugcucaac 19
<210> 148
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 148
agcaauucau uauacugaa 19
<210> 149
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 149
gugcuuguug uugaaaauu 19
<210> 150
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 150
cugcauguua augccucac 19
<210> 151
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 151
ccuccaacuu cagauugac 19
<210> 152
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 152
uccaacuuca gauugacuu 19
<210> 153
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 153
uaagaccuuu gaacugaau 19
<210> 154
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 154
agaccuuuga acugaaugu 19
<210> 155
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 155
cuuggcgacu uccacagaa 19
<210> 156
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 156
uggcgacuuc cacagaaaa 19
<210> 157
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 157
ugaccacuga gaagaagga 19
<210> 158
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 158
caggucugcu uucucaugu 19
<210> 159
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 159
cucaugugug agucaggga 19
<210> 160
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 160
gacacugacu gaauaguua 19
<210> 161
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 161
aaacucucac ugccacuac 19
<210> 162
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 162
ucucacugcc acuaccuuu 19
<210> 163
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 163
acuccgugaa gccacaagc 19
<210> 164
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 164
ugaagccaca agcaccuua 19
<210> 165
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 165
cacaagcacc uuauguccu 19
<210> 166
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 166
uucuuuuggg cauguucac 19
<210> 167
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 167
cuuuugggca uguucacag 19
<210> 168
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 168
ccaccaagaa gguuagcag 19
<210> 169
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 169
aagguuagca ggccaacag 19
<210> 170
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 170
gguuagcagg ccaacagcu 19
<210> 171
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 171
ucugacaucu aucuguaga 19
<210> 172
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 172
acaucuaucu guagaugcc 19
<210> 173
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 173
aucuaucugu agaugccag 19
<210> 174
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 174
uaccaacucu cagaucgcu 19
<210> 175
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 175
ccaacucuca gaucgcugg 19
<210> 176
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 176
gaucgcugga gcccuuaga 19
<210> 177
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 177
ccuuagacaa acuggaaag 19
<210> 178
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 178
cagagaugau acccuccca 19
<210> 179
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 179
ugauacccuc ccagcaagu 19
<210> 180
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 180
aaaggggcua cccagauca 19
<210> 181
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 181
gcuacccaga ucaggguug 19
<210> 182
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 182
cucaauuacc aggguggga 19
<210> 183
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 183
cuugucaccc agcauaucc 19
<210> 184
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 184
agccuaaagc cagauggac 19
<210> 185
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 185
ucugacauug cccauacuc 19
<210> 186
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 186
gagggaggcc aaaccauug 19
<210> 187
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 187
gggaggccaa accauugag 19
<210> 188
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 188
gaggccaaac cauugagac 19
<210> 189
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 189
uucuacagaa ccauggcuu 19
<210> 190
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 190
aaccauggcu ucuuucgga 19
<210> 191
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 191
cuucuuucgg aaaggucug 19
<210> 192
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 192
uuucggaaag gucugguug 19
<210> 193
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 193
uccaauacuu ugccaccca 19
<210> 194
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 194
augaacucag ggugugccc 19
<210> 195
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 195
agggugugcc cugggacac 19
<210> 196
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 196
cacugguuuu auauagucu 19
<210> 197
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 197
auagucuuuu ggcacaccu 19
<210> 198
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 198
agucuuuugg cacaccugu 19
<210> 199
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 199
uguucuguug acuucguuc 19
<210> 200
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 200
accuacuuuc ucaucuugg 19
<210> 201
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 201
ccuuacuuag cucuuaauc 19
<210> 202
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 202
agcucuuaau cucaucugu 19
<210> 203
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 203
uaaucucauc uguugaacu 19
<210> 204
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 204
aucucaucug uugaacuca 19
<210> 205
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 205
ucaagcugcc cauuuuaau 19
<210> 206
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 206
uuguugagag gauaguuuc 19
<210> 207
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 207
gugacaugau augauccac 19
<210> 208
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 208
ugauauuaau agccaaacg 19
<210> 209
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 209
auauuaauag ccaaacgaa 19
<210> 210
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 210
auuaauagcc aaacgaacu 19
<210> 211
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 211
uaauagccaa acgaacuuc 19
<210> 212
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 212
auagccaaac gaacuucaa 19
<210> 213
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 213
agccaaacga acuucaaaa 19
<210> 214
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 214
ccaaacgaac uucaaaaca 19
<210> 215
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 215
aaacgaacuu caaaacagc 19
<210> 216
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 216
agaggggaac cuaagauga 19
<210> 217
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 217
aggggaaccu aagaugagu 19
<210> 218
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 218
gggaaccuaa gaugaguaa 19
<210> 219
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 219
gaaccuaaga ugaguaaua 19
<210> 220
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 220
aguaauaugc caauccaag 19
<210> 221
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 221
uaauaugcca auccaagac 19
<210> 222
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 222
auaugccaau ccaagacug 19
<210> 223
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 223
acuaaagcug acagguucc 19
<210> 224
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 224
uuuggggugg gauagacau 19
<210> 225
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 225
auuauuacac aaucuggcu 19
<210> 226
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 226
uauuacacaa ucuggcuca 19
<210> 227
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 227
ucauguacag gaucacuuu 19
<210> 228
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 228
guuacacuag guuacauuu 19
<210> 229
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 229
uuaauagguc cuuuacauc 19
<210> 230
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 230
gugauacaca gauugaauu 19
<210> 231
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 231
auaucucucc uuguaaaua 19
<210> 232
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 232
auacuagaag cucuccuuu 19
<210> 233
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 233
acuagaagcu cuccuuuac 19
<210> 234
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 234
uggguuuccc aauugugac 19
<210> 235
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 235
agcaguguaa uuaaaagca 19
<210> 236
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 236
gcaacaacug gauuacucc 19
<210> 237
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 237
aacaacugga uuacuccaa 19
<210> 238
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 238
cuagggaaaa auagccuac 19
<210> 239
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 239
agggaaaaau agccuacac 19
<210> 240
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 240
agccuacaca agccuuuag 19
<210> 241
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 241
ccuacacaag ccuuuaggc 19
<210> 242
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 242
uacacaagcc uuuaggccu 19
<210> 243
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 243
cacaagccuu uaggccuac 19
<210> 244
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 244
caagccuuua ggccuacuc 19
<210> 245
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 245
ggguuugagu gaacaaagg 19
<210> 246
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 246
uuuggccauu gauguucua 19
<210> 247
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 247
uggccauuga uguucuagc 19
<210> 248
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 248
uugcaugcgc ucugcucua 19
<210> 249
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 249
gcaugcgcuc ugcucuaca 19
<210> 250
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 250
augcgcucug cucuacaaa 19
<210> 251
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 251
ugcucuacaa acagaguug 19
<210> 252
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 252
cucuacaaac agaguuggu 19
<210> 253
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 253
uaugguuggu auacuguac 19
<210> 254
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 254
gccacucaga cccacuuag 19
<210> 255
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 255
cacucagacc cacuuagcu 19
<210> 256
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 256
cacuuagcug gugagcuag 19
<210> 257
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 257
cuuagcuggu gagcuagaa 19
<210> 258
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 258
aaguuggcag ugcucgaug 19
<210> 259
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 259
guuggcagug cucgaugug 19
<210> 260
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 260
ugcucgaugu ggacgaaga 19
<210> 261
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 261
cucgaugugg acgaagagu 19
<210> 262
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 262
ggacgaagag ugaggaaga 19
<210> 263
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 263
ucaaagaaaa gagucgugu 19
<210> 264
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 264
gcaguuucag cucucguuc 19
<210> 265
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 265
uuucagcucu cguucauug 19
<210> 266
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 266
agcucucguu cauugggca 19
<210> 267
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 267
cucucguuca uugggcagc 19
<210> 268
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 268
cucguucauu gggcagcuc 19
<210> 269
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 269
cguucauugg gcagcucgc 19
<210> 270
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 270
acaugggagu uguuggauu 19
<210> 271
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 271
uuuucuaugc cauaggcaa 19
<210> 272
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 272
uucuaugcca uaggcaaua 19
<210> 273
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 273
uacucugaga aagggauau 19
<210> 274
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 274
uugaaggacu gucauauau 19
<210> 275
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 275
uuuauguaug uucacuggc 19
<210> 276
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 276
uauguauguu cacuggcac 19
<210> 277
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 277
ggcacuaaaa aauauagag 19
<210> 278
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 278
aaaaaauaua gagagcuuc 19
<210> 279
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 279
gguugaaaaa uaaugugcu 19
<210> 280
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 280
ugaugcuaga gucccucuc 19
<210> 281
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 281
augcuagagu cccucucug 19
<210> 282
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 282
gucccucucu guccauacu 19
<210> 283
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 283
uagcaaguuu uauuugacu 19
<210> 284
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 284
agcuaacauu gagcuucaa 19
<210> 285
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 285
guuuguuuca uuaggcaca 19
<210> 286
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 286
uuguuucauu aggcacagc 19
<210> 287
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 287
cauuaggcac agcacagau 19
<210> 288
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 288
cagggcauaa aggcccagg 19
<210> 289
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 289
accaaagcug cauuucagg 19
<210> 290
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 290
ucaggagacu cucuccaga 19
<210> 291
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 291
cuccagacag cccaguaac 19
<210> 292
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 292
acagcccagu aacuacccg 19
<210> 293
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 293
agcccaguaa cuacccgag 19
<210> 294
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 294
cccaguaacu acccgagca 19
<210> 295
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 295
caguaacuac ccgagcaug 19
<210> 296
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 296
guaacuaccc gagcauggc 19
<210> 297
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 297
agaggcugac ugucuacga 19
<210> 298
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 298
aggcugacug ucuacgaau 19
<210> 299
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 299
gcugacuguc uacgaauua 19
<210> 300
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 300
ugacugucua cgaauuauc 19
<210> 301
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 301
acugucuacg aauuaucuu 19
<210> 302
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 302
uacgaauuau cuugugcca 19
<210> 303
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 303
cgaauuaucu ugugccagu 19
<210> 304
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 304
gguuuucaug uuugaccca 19
<210> 305
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 305
uuuucauguu ugacccacu 19
<210> 306
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 306
uucuaccccu gaugccuuu 19
<210> 307
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 307
uguaggcaga ucuguucuc 19
<210> 308
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 308
uaggcagauc uguucucac 19
<210> 309
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 309
gauuacauug uaccugcua 19
<210> 310
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 310
uuacauugua ccugcuaag 19
<210> 311
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 311
auuguaccug cuaagauac 19
<210> 312
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 312
aauucauaag ggcaggggg 19
<210> 313
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 313
gggggggagc aagcauuag 19
<210> 314
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 314
gggggagcaa gcauuagug 19
<210> 315
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 315
gggagcaagc auuagugcc 19
<210> 316
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 316
cucuuugaua agcugucca 19
<210> 317
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 317
uugauaagcu guccaaaga 19
<210> 318
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 318
acagacuaaa ggacucugc 19
<210> 319
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 319
cuggugacug acuuauaag 19
<210> 320
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 320
ggugacugac uuauaagag 19
<210> 321
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 321
acugacuuau aagagcuuu 19
<210> 322
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 322
auggguccuu cacuaagug 19
<210> 323
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 323
uuauaagcag aacuggcuu 19
<210> 324
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 324
uuuucucuag uaguugcug 19
<210> 325
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 325
cucuaguagu ugcugagca 19
<210> 326
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 326
gcaaauuguu gaagcucca 19
<210> 327
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 327
uguugaagcu ccaucauug 19
<210> 328
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 328
uugaagcucc aucauugca 19
<210> 329
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 329
gaagcuccau cauugcaug 19
<210> 330
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 330
agcuccauca uugcauggu 19
<210> 331
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 331
cuccaucauu gcaugguug 19
<210> 332
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 332
ccaucauugc augguugga 19
<210> 333
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 333
aucauugcau gguuggaaa 19
<210> 334
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 334
agccacugug uuugcuagu 19
<210> 335
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 335
ugcuagugcc cauguuagc 19
<210> 336
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 336
cuagugccca uguuagcuu 19
<210> 337
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 337
gcugauaagg gagcauuua 19
<210> 338
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 338
ugauaaggga gcauuuaaa 19
<210> 339
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 339
gggagcauuu aaaguacua 19
<210> 340
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 340
ggcacaaaaa guuaucugc 19
<210> 341
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 341
guuaucugca guugaaggc 19
<210> 342
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 342
guguguguuc ugauagcuu 19
<210> 343
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 343
ugagagagga ugcaguuuu 19
<210> 344
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 344
acaccuggau ugaucaguu 19
<210> 345
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 345
accuggauug aucaguuaa 19
<210> 346
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 346
cuggauugau caguuaacu 19
<210> 347
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 347
ggauugauca guuaacuaa 19
<210> 348
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 348
ugaucaguua acuaaaagu 19
<210> 349
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 349
aucaguuaac uaaaaguuu 19
<210> 350
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 350
caguuaacua aaaguuuuc 19
<210> 351
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 351
ccccuauugg guuugaccc 19
<210> 352
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 352
ccuauugggu uugacccac 19
<210> 353
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 353
ggguuugacc cacaggucc 19
<210> 354
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 354
agggauaaaa agaguagag 19
<210> 355
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 355
uagaggacau gauacauug 19
<210> 356
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 356
gaggacauga uacauugua 19
<210> 357
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 357
gauacauugu acuuuacua 19
<210> 358
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 358
uuuacuaguu caagacaga 19
<210> 359
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 359
cuaguucaag acagaugaa 19
<210> 360
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 360
ccuacccaag ugauugacc 19
<210> 361
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 361
auugaccagu ggcccccua 19
<210> 362
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 362
ugaccagugg cccccuaau 19
<210> 363
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 363
guggcccccu aaugggacc 19
<210> 364
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 364
cccuaauggg accugagcu 19
<210> 365
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 365
cuaaugggac cugagcugu 19
<210> 366
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 366
gggcaguuuc cugcauugg 19
<210> 367
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 367
gcauuggaac cuggagcaa 19
<210> 368
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 368
gaaccuggag caagcgcuc 19
<210> 369
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 369
ggagcaagcg cucuaucuu 19
<210> 370
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 370
agcaagcgcu cuaucuuuc 19
<210> 371
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 371
caagcgcucu aucuuucac 19
<210> 372
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 372
agcgcucuau cuuucacac 19
<210> 373
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 373
uucacacaaa uucccucac 19
<210> 374
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 374
cacacaaauu cccucaccu 19
<210> 375
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 375
ugaggugcuc uuguuacug 19
<210> 376
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 376
aggugcucuu guuacuggg 19
<210> 377
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 377
gugcucuugu uacugggug 19
<210> 378
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 378
gcucuuguua cuggguguc 19
<210> 379
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 379
uuguuacugg gugucugug 19
<210> 380
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 380
cugugugcug uaauucugg 19
<210> 381
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 381
gugugcugua auucugguu 19
<210> 382
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 382
uucucuguua aaacuuguc 19
<210> 383
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 383
aaacuuguca gaguacuag 19
<210> 384
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 384
acuugucaga guacuagaa 19
<210> 385
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 385
uugucagagu acuagaagu 19
<210> 386
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 386
guacuagaag uuguaucuc 19
<210> 387
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 387
uuguaucucu guaggugca 19
<210> 388
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 388
ugauuaagag auugacacu 19
<210> 389
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 389
auuaagagau ugacacuuc 19
<210> 390
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 390
uaagagauug acacuucug 19
<210> 391
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 391
acacuucugu ugccuagga 19
<210> 392
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 392
acuucuguug ccuaggacc 19
<210> 393
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 393
uucuguugcc uaggaccuc 19
<210> 394
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 394
cuguugccua ggaccuccc 19
<210> 395
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 395
aggugaaggc agaaaaauc 19
<210> 396
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 396
auuaguuacu ccucuucag 19
<210> 397
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 397
uaguuacucc ucuucagac 19
<210> 398
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 398
auuuggccag aaaguaggu 19
<210> 399
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 399
aguagguaau augcauuga 19
<210> 400
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 400
uagguaauau gcauugauu 19
<210> 401
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 401
gguaauaugc auugauugg 19
<210> 402
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 402
auaugcauug auuggcuuc 19
<210> 403
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 403
augcauugau uggcuucug 19
<210> 404
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 404
uucaguauag caaggugcu 19
<210> 405
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 405
caguauagca aggugcuag 19
<210> 406
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 406
guauagcaag gugcuaggu 19
<210> 407
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 407
caaggugcua gguuuuuuc 19
<210> 408
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 408
cuuagaaugg guggcccuu 19
<210> 409
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 409
ucccacauaa gcuacuuaa 19
<210> 410
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 410
ccacauaagc uacuuaaca 19
<210> 411
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 411
cuuaacaaga uugucaugg 19
<210> 412
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 412
gagcugcaga uuccauugc 19
<210> 413
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 413
auugcccacc aaagacuag 19
<210> 414
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 414
guaugggaac cuguacucu 19
<210> 415
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 415
uuugcauuau cucacaacc 19
<210> 416
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 416
ugcauuaucu cacaaccuu 19
<210> 417
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 417
cauuaucuca caaccuuag 19
<210> 418
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 418
cacaaccuua gcccuuggu 19
<210> 419
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 419
caaccuuagc ccuuggugc 19
<210> 420
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 420
cuuagcccuu ggugcuaac 19
<210> 421
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 421
uagcccuugg ugcuaacug 19
<210> 422
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 422
uuggugcuaa cuguccuac 19
<210> 423
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 423
cuaacugucc uacagugaa 19
<210> 424
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 424
aacuguccua cagugaagu 19
<210> 425
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 425
gugaagugcc ugggggguu 19
<210> 426
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 426
gaagugccug ggggguugu 19
<210> 427
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 427
ccuggggggu uguccuauc 19
<210> 428
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 428
ugggggguug uccuauccc 19
<210> 429
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 429
ggggguuguc cuaucccau 19
<210> 430
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 430
ggguuguccu aucccauaa 19
<210> 431
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 431
guuguccuau cccauaagc 19
<210> 432
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 432
uguccuaucc cauaagcca 19
<210> 433
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 433
uccuauccca uaagccacu 19
<210> 434
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 434
gaaugaccca cgcaaaaaa 19
<210> 435
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 435
aaaguccccu cacaaccca 19
<210> 436
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 436
aguccccuca caacccagu 19
<210> 437
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 437
uccccucaca acccaguga 19
<210> 438
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 438
caacccagug acaccuuuc 19
<210> 439
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 439
acccagugac accuuucug 19
<210> 440
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 440
uccucuagac uggaacauu 19
<210> 441
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 441
cucuagacug gaacauuga 19
<210> 442
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 442
gggagugccu cagacauga 19
<210> 443
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 443
gagugccuca gacaugaca 19
<210> 444
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 444
gugccucaga caugacauu 19
<210> 445
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 445
agacuaugua aacagagau 19
<210> 446
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 446
uuuagauggg gcucauuuc 19
<210> 447
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 447
ucauuucuca cgguggcac 19
<210> 448
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 448
auuucucacg guggcacuu 19
<210> 449
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 449
ccagcuccaa gcgcuagug 19
<210> 450
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 450
agcuccaagc gcuaguguu 19
<210> 451
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 451
ccaagcgcua guguucugu 19
<210> 452
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 452
aagcgcuagu guucuguuc 19
<210> 453
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 453
ggaaucuuuu guugcucua 19
<210> 454
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 454
aaauggcaga aacuuguuu 19
<210> 455
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 455
aaugucaucc auuguguaa 19
<210> 456
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 456
aaauauuggc uuacugguc 19
<210> 457
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 457
auauuggcuu acuggucug 19
<210> 458
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 458
ccacaucccc uguuauggc 19
<210> 459
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 459
acauccccug uuauggcug 19
<210> 460
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 460
ccccuguuau ggcugcagg 19
<210> 461
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 461
ccuguuaugg cugcaggau 19
<210> 462
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 462
uguuauggcu gcaggaucg 19
<210> 463
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 463
cugcaggauc gaguuauug 19
<210> 464
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 464
gcaggaucga guuauuguu 19
<210> 465
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 465
aggaucgagu uauuguuaa 19
<210> 466
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 466
gaucgaguua uuguuaaca 19
<210> 467
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 467
auguccucuu aucauuguu 19
<210> 468
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 468
guccucuuau cauuguugu 19
<210> 469
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 469
gugcaguuag ggcugggaa 19
<210> 470
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 470
gggucuaccc ucggccgcc 19
<210> 471
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 471
ucuguuccag agcgugcgc 19
<210> 472
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 472
gugauccaga acccgggcc 19
<210> 473
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 473
cagcaaccuu cacagccgc 19
<210> 474
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 474
ggggcugccg cagcagcug 19
<210> 475
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 475
agacauccug agcgaggcc 19
<210> 476
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 476
cuccuucagc aacagcagc 19
<210> 477
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 477
ggcagcagca gcgggagag 19
<210> 478
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 478
ggacaauuac uuagggggc 19
<210> 479
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 479
uuacuuaggg ggcacuucg 19
<210> 480
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 480
ggcagugucg guguccaug 19
<210> 481
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 481
cagcuucggg gggauugca 19
<210> 482
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 482
ugcaaagguu cucugcuag 19
<210> 483
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 483
agguucucug cuagacgac 19
<210> 484
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 484
gagcacugaa gauacugcu 19
<210> 485
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 485
gauacugcug aguauuccc 19
<210> 486
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 486
gggagguuac accaaaggg 19
<210> 487
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 487
ggcgagagcc uaggcugcu 19
<210> 488
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 488
guccggagca cuggacgag 19
<210> 489
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 489
cuuuccacug gcucuggcc 19
<210> 490
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 490
gcuggagaac ccgcuggac 19
<210> 491
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 491
cccgcuggac uacggcagc 19
<210> 492
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 492
gaaggccagu uguauggac 19
<210> 493
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 493
ggccaguugu auggaccgu 19
<210> 494
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 494
aagcgaaaug ggccccugg 19
<210> 495
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 495
gcgaaauggg ccccuggau 19
<210> 496
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 496
augggccccu ggauggaua 19
<210> 497
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 497
gcuucugggu gucacuaug 19
<210> 498
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 498
ggucuucuuc aaaagagcc 19
<210> 499
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 499
aagagccgcu gaagggaaa 19
<210> 500
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 500
gagccgcuga agggaaaca 19
<210> 501
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 501
gggaaacaga aguaccugu 19
<210> 502
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 502
acagaaguac cugugcgcc 19
<210> 503
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 503
guaccugugc gccagcaga 19
<210> 504
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 504
auuccgaagg aaaaauugu 19
<210> 505
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 505
ggaaaaauug uccaucuug 19
<210> 506
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 506
aaauugucca ucuugucgu 19
<210> 507
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 507
auuguccauc uugucgucu 19
<210> 508
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 508
gcagggauga cucugggag 19
<210> 509
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 509
gcugaagaaa cuugguaau 19
<210> 510
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 510
gaaacuuggu aaucugaaa 19
<210> 511
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 511
acuugguaau cugaaacua 19
<210> 512
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 512
ggagaggcuu ccagcacca 19
<210> 513
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 513
ggcuaugaau gucagccca 19
<210> 514
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 514
ugucagccca ucuuucuga 19
<210> 515
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 515
caaccagccc gacuccuuu 19
<210> 516
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 516
ccagcccgac uccuuugca 19
<210> 517
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 517
ugaacuggga gagagacag 19
<210> 518
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 518
cugggagaga gacagcuug 19
<210> 519
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 519
ggccuugccu ggcuuccgc 19
<210> 520
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 520
cuuacacgug gacgaccag 19
<210> 521
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 521
ugaguaccgc augcacaag 19
<210> 522
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 522
ugaggcaccu cucucaaga 19
<210> 523
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 523
gaguuuggau ggcuccaaa 19
<210> 524
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 524
uuccugugca ugaaagcac 19
<210> 525
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 525
agcacugcua cucuucagc 19
<210> 526
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 526
aaaucaaaaa uucuuugau 19
<210> 527
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 527
aucaaaaauu cuuugauga 19
<210> 528
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 528
aaauucuuug augaacuuc 19
<210> 529
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 529
auucuuugau gaacuucga 19
<210> 530
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 530
cuucgaauga acuacauca 19
<210> 531
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 531
ugaacuacau caaggaacu 19
<210> 532
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 532
cuacaucaag gaacucgau 19
<210> 533
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 533
aagaaaaaau cccacaucc 19
<210> 534
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 534
gaaaaaaucc cacauccug 19
<210> 535
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 535
aaaaucccac auccugcuc 19
<210> 536
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 536
aaucccacau ccugcucaa 19
<210> 537
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 537
ucccacaucc ugcucaaga 19
<210> 538
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 538
gcuccuggac uccgugcag 19
<210> 539
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 539
ucaagucaca cauggugag 19
<210> 540
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 540
gucacacaug gugagcgug 19
<210> 541
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 541
gugcccaaga uccuuucug 19
<210> 542
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 542
gauccuuucu gggaaaguc 19
<210> 543
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 543
agucaagccc aucuauuuc 19
<210> 544
<211> 19
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 544
gcccaucuau uuccacacc 19
<210> 545
<211> 12
<212> RNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 靶向雄激素受体的SiRNA有义链(SiRNA sense strand for targetingAdrogen Receptor)
<400> 545
aaaaaaaaaa aa 12
Claims (29)
1.一种双链寡核苷酸构建体,所述双链寡核苷酸构建体具有以下结构式(1)的结构:
A-X-R-Y-B 结构式(1)
在结构式(1)中,其中A为亲水性物质,B为疏水性物质,X和Y中的每一个独立地表示简单的共价键或接头介导的共价键,并且R表示雄激素受体特异性寡核苷酸,所述雄激素受体特异性寡核苷酸包含含有选自SEQ ID NO:6、58、68、99、107、109、260、270、284、298、348、358、359和434的任一序列的有义链和含有与其互补的序列的反义链。
4.根据权利要求1所述的双链寡核苷酸构建体,其中所述亲水性物质的分子量为200至10,000。
5.根据权利要求4所述的双链寡核苷酸构建体,其中所述亲水性物质选自聚乙二醇(PEG)、聚乙烯吡咯烷酮和聚噁唑啉中的任一种。
7.根据权利要求1所述的双链寡核苷酸构建体,其中所述疏水性物质的分子量为250至1,000。
8.根据权利要求7所述的双链寡核苷酸构建体,其中所述疏水性物质选自类固醇衍生物、甘油酯衍生物、甘油醚、聚丙二醇、C12-C50不饱和或饱和烃、二酰基磷脂酰胆碱、脂肪酸、磷脂和脂多胺。
9.根据权利要求8所述的双链寡核苷酸构建体,其中所述类固醇衍生物选自胆固醇、胆甾烷醇、胆酸、胆甾醇基甲酸酯、胆甾烷基甲酸酯和胆甾醇胺。
10.根据权利要求8所述的双链寡核苷酸构建体,其中所述甘油酯衍生物选自甘油单酯、甘油二酯和甘油三酯。
11.根据权利要求1所述的双链寡核苷酸构建体,其中由X和Y表示的所述共价键为不可裂解键或可裂解键。
12.根据权利要求11所述的双链寡核苷酸构建体,其中所述不可裂解键为酰胺键或磷酸酯键。
13.根据权利要求11所述的双链寡核苷酸构建体,其中所述可裂解键为二硫键、酸可裂解键、酯键、酸酐键、生物可降解键或酶可裂解键。
14.根据权利要求1所述的双链寡核苷酸构建体,其中具有与通过受体介导的内吞作用(RME)促进靶细胞内化的受体特异性结合的特性的配体另外地与所述亲水性物质结合。
15.根据权利要求14所述的双链寡核苷酸构建体,其中所述配体选自靶受体特异性抗体、适配体、肽、叶酸、N-乙酰基半乳糖胺(NAG)、葡萄糖和甘露糖。
16.根据权利要求1所述的双链寡核苷酸构建体,其中在与所述寡核苷酸结合的末端部分相对的所述亲水性物质末端部分处另外引入胺基团或多组氨酸基团。
17.根据权利要求16所述的双链寡核苷酸构建体,其中所述胺基团或所述多组氨酸基团通过至少一个接头与所述亲水性物质或亲水性嵌段连接。
18.根据权利要求16所述的双链寡核苷酸构建体,其中所述胺基团是选自伯胺基团至叔胺基团的任一种。
19.根据权利要求16所述的双链寡核苷酸构建体,其中所述多组氨酸基团包含3至10个组氨酸。
20.一种纳米颗粒,所述纳米颗粒包含根据权利要求1至19中任一项所述的双链寡核苷酸构建体。
21.根据权利要求20所述的纳米颗粒,其中将包含具有不同序列的寡核苷酸的双链寡核苷酸构建体混合。
22.一种用于预防脱发或促进头发生长的药物组合物,所述药物组合物包含根据权利要求1至19中任一项所述的双链寡核苷酸构建体作为活性成分。
23.一种用于预防脱发或促进头发生长的药物组合物,所述药物组合物包含根据权利要求20所述的纳米颗粒作为活性成分。
24.根据权利要求22所述的药物组合物,其中所述药物组合物用于选自膏剂、糊剂、凝胶、冻胶、血清、气溶胶喷雾剂、非气溶胶喷雾剂、泡沫、霜剂、洗剂、溶液和混悬液配制品的配制品。
25.根据权利要求23所述的药物组合物,其中所述药物组合物用于选自膏剂、糊剂、凝胶、冻胶、血清、气溶胶喷雾剂、非气溶胶喷雾剂、泡沫、霜剂、洗剂、溶液和混悬液配制品的配制品。
26.一种用于预防脱发或促进头发生长的化妆品组合物,所述化妆品组合物包含根据权利要求1至19中任一项所述的双链寡核苷酸构建体作为活性成分。
27.一种用于预防脱发或促进头发生长的化妆品组合物,所述化妆品组合物包含根据权利要求20所述的纳米颗粒作为活性成分。
28.根据权利要求26所述的化妆品组合物,其中所述组合物用于选自以下的配制品:生发液、头发调理剂、头发精华、头发洗剂、头发营养洗剂、洗发香波、护发素、头发处理剂、发膏、营养发膏、保湿发膏、按摩发膏、发蜡、发用气溶胶、发膜、营养发膜、洗发皂、头发清洁泡沫、发油、干发剂、头发保护剂、染发剂、卷发剂、头发脱色剂、发胶、发釉、头发敷料、粘发剂、头发保湿剂、发用摩丝和喷发配制品。
29.根据权利要求27所述的化妆品组合物,其中所述组合物用于选自以下的配制品:生发液、头发调理剂、头发精华、头发洗剂、头发营养洗剂、洗发香波、护发素、头发处理剂、发膏、营养发膏、保湿发膏、按摩发膏、发蜡、发用气溶胶、发膜、营养发膜、洗发皂、头发清洁泡沫、发油、干发剂、头发保护剂、染发剂、卷发剂、头发脱色剂、发胶、发釉、头发敷料、粘发剂、头发保湿剂、发用摩丝和喷发配制品。
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KR1020180149562A KR102473989B1 (ko) | 2018-11-28 | 2018-11-28 | 안드로젠 수용체 특이적 서열을 포함하는 이중나선 올리고뉴클레오티드 구조체, 및 이를 포함하는 탈모 예방 및 발모용 조성물 |
PCT/KR2019/015723 WO2020111614A1 (ko) | 2018-11-28 | 2019-11-18 | 안드로젠 수용체 특이적 서열을 포함하는 이중나선 올리고뉴클레오티드 구조체, 및 이를 포함하는 탈모 예방 및 발모용 조성물 |
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JP2024509906A (ja) * | 2021-03-08 | 2024-03-05 | バイオニア コーポレーション | Covid‐19を含む呼吸器系ウイルス感染症、ウイルス感染を原因とする肺線維症、又は呼吸器疾患の予防又は治療のために超音波ネブライザを使用して二本鎖オリゴヌクレオチド構造物を投与するための組成物 |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070141009A1 (en) * | 2003-01-03 | 2007-06-21 | Shaharyar Khan | Sirna mediated post-transriptional gene silencing of genes involved in alopecia |
CN101054579A (zh) * | 2007-03-29 | 2007-10-17 | 上海复旦新杨生物科技有限责任公司 | 一种防治脱发和促进生发的siRNA及其制备方法和应用 |
CN101291948A (zh) * | 2004-09-28 | 2008-10-22 | 夸克医药公司 | 寡核糖核苷酸以及其用于治疗脱发、肾衰竭和其它疾病的方法 |
CN101932709A (zh) * | 2007-11-26 | 2010-12-29 | 桑塔里斯制药公司 | 靶向雄激素受体的lna拮抗剂 |
CN102439148A (zh) * | 2009-05-14 | 2012-05-02 | 株式会社百奥尼 | siRNA缀合物及其制备方法 |
CN105683377A (zh) * | 2013-07-05 | 2016-06-15 | 柏业公司 | 呼吸疾病相关基因特异性siRNA、含有siRNA的双螺旋寡RNA结构、含有它们的组合物用于预防或治疗呼吸疾病 |
CN105705639A (zh) * | 2013-07-05 | 2016-06-22 | 柏业公司 | 登革病毒相关的基因特异性siRNA、包含该siRNA的双链寡RNA分子、和包含它们的用于抑制登革病毒复制的组合物 |
CN105705638A (zh) * | 2013-07-05 | 2016-06-22 | 柏业公司 | 改善的具有高效能的纳米颗粒型寡核苷酸结构及其制备方法 |
CN105722979A (zh) * | 2013-07-09 | 2016-06-29 | 柏业公司 | 肝癌相关的基因特异性siRNA、包含所述siRNA的双链寡RNA分子和包含它们的用于预防或治疗癌症的组合物 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6005087A (en) | 1995-06-06 | 1999-12-21 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
US5660985A (en) | 1990-06-11 | 1997-08-26 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands containing modified nucleotides |
US5386023A (en) | 1990-07-27 | 1995-01-31 | Isis Pharmaceuticals | Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling |
AU2666797A (en) | 1996-04-15 | 1997-11-07 | Dyad Pharmaceutical Corporation | Combination therapy for androgenic alopecia with antisense oligonucleotides and minoxidil |
US6277967B1 (en) | 1998-07-14 | 2001-08-21 | Isis Pharmaceuticals, Inc. | Carbohydrate or 2′-modified oligonucleotides having alternating internucleoside linkages |
US6175001B1 (en) | 1998-10-16 | 2001-01-16 | The Scripps Research Institute | Functionalized pyrimidine nucleosides and nucleotides and DNA's incorporating same |
EP1449538A1 (en) * | 2003-02-21 | 2004-08-25 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibition of TACE or amphiregulin for the modulation of EGF receptor signal transactivation |
WO2005045037A2 (en) | 2003-10-23 | 2005-05-19 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF 5-ALPHA REDUCTASE AND ANDROGEN RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
CN101287835A (zh) | 2005-08-17 | 2008-10-15 | 株式会社百奥尼 | 用于siRNA细胞内输送的siRNA-亲水性聚合物结合物及其方法 |
CA2804210A1 (en) * | 2010-07-06 | 2012-01-12 | Dicerna Pharmaceuticals, Inc. | Methods and compositions for the specific inhibition of androgen receptor by double-stranded rna |
KR101241852B1 (ko) * | 2012-06-28 | 2013-03-11 | (주)바이오니아 | siRNA 접합체 및 그 제조방법 |
SG11201500184TA (en) | 2012-07-27 | 2015-04-29 | Aragon Pharmaceuticals Inc | Methods and compositions for determining resistance to androgen receptor therapy |
US9175291B2 (en) | 2012-10-11 | 2015-11-03 | Isis Pharmaceuticals Inc. | Modulation of androgen receptor expression |
KR20160110298A (ko) | 2016-08-31 | 2016-09-21 | 박상민 | 쓰레기통 발전기 |
KR102321426B1 (ko) * | 2017-02-21 | 2021-11-05 | 올릭스 주식회사 | 남성형 탈모 표적 유전자의 발현을 억제하는 비대칭 siRNA |
-
2018
- 2018-11-28 KR KR1020180149562A patent/KR102473989B1/ko active IP Right Grant
-
2019
- 2019-11-18 EP EP19890073.0A patent/EP3888686A4/en active Pending
- 2019-11-18 CN CN201980087853.4A patent/CN113271980B/zh active Active
- 2019-11-18 MX MX2021006130A patent/MX2021006130A/es unknown
- 2019-11-18 BR BR112021010344A patent/BR112021010344A2/pt unknown
- 2019-11-18 US US17/297,193 patent/US20220118093A1/en active Pending
- 2019-11-18 AU AU2019390969A patent/AU2019390969B2/en active Active
- 2019-11-18 WO PCT/KR2019/015723 patent/WO2020111614A1/ko unknown
- 2019-11-18 JP JP2021530850A patent/JP2022513662A/ja active Pending
- 2019-11-18 CA CA3121472A patent/CA3121472A1/en active Pending
-
2023
- 2023-06-07 JP JP2023093713A patent/JP2023113845A/ja active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070141009A1 (en) * | 2003-01-03 | 2007-06-21 | Shaharyar Khan | Sirna mediated post-transriptional gene silencing of genes involved in alopecia |
CN101291948A (zh) * | 2004-09-28 | 2008-10-22 | 夸克医药公司 | 寡核糖核苷酸以及其用于治疗脱发、肾衰竭和其它疾病的方法 |
CN101054579A (zh) * | 2007-03-29 | 2007-10-17 | 上海复旦新杨生物科技有限责任公司 | 一种防治脱发和促进生发的siRNA及其制备方法和应用 |
CN101932709A (zh) * | 2007-11-26 | 2010-12-29 | 桑塔里斯制药公司 | 靶向雄激素受体的lna拮抗剂 |
CN102439148A (zh) * | 2009-05-14 | 2012-05-02 | 株式会社百奥尼 | siRNA缀合物及其制备方法 |
CN105683377A (zh) * | 2013-07-05 | 2016-06-15 | 柏业公司 | 呼吸疾病相关基因特异性siRNA、含有siRNA的双螺旋寡RNA结构、含有它们的组合物用于预防或治疗呼吸疾病 |
CN105705639A (zh) * | 2013-07-05 | 2016-06-22 | 柏业公司 | 登革病毒相关的基因特异性siRNA、包含该siRNA的双链寡RNA分子、和包含它们的用于抑制登革病毒复制的组合物 |
CN105705638A (zh) * | 2013-07-05 | 2016-06-22 | 柏业公司 | 改善的具有高效能的纳米颗粒型寡核苷酸结构及其制备方法 |
CN105722979A (zh) * | 2013-07-09 | 2016-06-29 | 柏业公司 | 肝癌相关的基因特异性siRNA、包含所述siRNA的双链寡RNA分子和包含它们的用于预防或治疗癌症的组合物 |
Non-Patent Citations (1)
Title |
---|
程美,等: "雄激素及其受体在雄激素性脱发中的作用", 西南军医, vol. 19, no. 04, pages 335 - 338 * |
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EP3888686A1 (en) | 2021-10-06 |
KR102473989B1 (ko) | 2022-12-07 |
AU2019390969B2 (en) | 2023-03-09 |
BR112021010344A2 (pt) | 2021-11-30 |
AU2019390969A1 (en) | 2021-07-08 |
KR20200064233A (ko) | 2020-06-08 |
EP3888686A4 (en) | 2023-02-08 |
JP2022513662A (ja) | 2022-02-09 |
US20220118093A1 (en) | 2022-04-21 |
WO2020111614A1 (ko) | 2020-06-04 |
CA3121472A1 (en) | 2020-06-04 |
CN113271980B (zh) | 2024-02-02 |
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JP2023113845A (ja) | 2023-08-16 |
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