CN114316070A - 用于治疗肌营养不良症的转基因表达盒 - Google Patents
用于治疗肌营养不良症的转基因表达盒 Download PDFInfo
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Abstract
本发明涉及可用于治疗肌营养不良症的重组杂合蛋白、编码该重组杂合蛋白的核酸分子、包含该核酸分子的转基因表达盒以及包含该转基因表达盒的基因递送***。本公开的核酸分子、转基因表达盒和基因递送***可以在肌肉组织中稳定表达治疗性蛋白,由此实现对肌营养不良症的良好治疗效果。
Description
技术领域
本公开涉及可用于治疗肌营养不良症的重组杂合蛋白、编码该重组杂合蛋白的核酸分子、包含该核酸分子的转基因表达盒以及包含该转基因表达盒的基因递送***。
背景技术
肌营养不良症(Muscular dystrophy,MD)是一种广泛的肌肉退行性疾病,主要表现为不同部位的肌肉功能缺陷,例如肌肉不同程度的进行性萎缩和无力。其中,最常见且进展最迅速的是杜氏型肌营养不良症(Duchenne muscular dystrophy,DMD)。杜氏型肌营养不良症是一种严重的X连锁隐性遗传的进行性神经肌肉疾病。由于缺乏肌营养不良蛋白(Dystrophin),DMD患者的骨骼肌、心脏和呼吸肌肉会逐渐退化。据统计,全球大约每3600个男孩中就有1人患有这种疾病。DMD患者在12至15岁时逐渐无法独立行走,必须使用轮椅,进而出现呼吸困难、呼吸道感染和吞咽问题,最终发展成心肌病,导致死亡。X连锁隐性遗传的肌营养不良症还包括贝克型肌营养不良症((Becker muscular dystrophy,BMD),其特征为肌肉活检样本中,肌营养不良蛋白的数量或质量下降。
肌营养不良蛋白基因是已知最大的人类基因,大约2.5Mb,主要在骨骼肌和心肌中表达。该基因位于X染色体的Xp21位置,包含79个外显子。DMD由肌营养不良蛋白基因突变导致。DMD最常见的突变类型包括一个或多个外显子的大片段的缺失突变(60-70%)、重复突变(5-10%)、单核苷酸变异(包括小删除或***,单碱基变化和剪切位点变化)。肌营养不良蛋白的基本功能是在收缩过程中通过N端结构域与F-肌动蛋白结合,同时通过C端结构域与β-肌营养不良蛋白聚糖结合,起到桥接和锚定蛋白的作用来稳定肌纤维。肌营养不良蛋白表达的缺失会导致严重的肌肉萎缩、呼吸和心力衰竭,原因是肌营养不良蛋白功能的丧失,破坏了其相关糖蛋白复合物(DGC)的形成,导致肌膜不稳定,对损伤的敏感性增加,以及纤维坏死(Findlay A R,Wein N,Kaminoh Y等,Clinical phenotypes as predictors ofthe outcome of skipping around DMD exon 45[J].Ann Neurol,2015,77(4):668-74)。因此,增加肌营养不良蛋白的表达对于肌营养不良的治疗十分关键。
对于肌营养不良症的治疗,目前还没有有效药物。糖皮质激素治疗是主要的保守治疗方法,但只能延缓一两年的疾病进展。因此,亟需获得用于治疗肌营养不良症的有效药物。
目前,腺相关病毒(adeno-associated virus,AAV)载体介导的基因导入在治疗单基因遗传罕见病方面发挥着巨大作用。AAV具有低致病性以及在各种器官组织中长期稳定表达蛋白的能力,这些特性使AAV在基因治疗领域具有明显的优势,适用于递送治疗性基因。AAV给肌营养不良症的治疗带来巨大希望。然而,AAV载体包装基因的大小限制在4.7kb,难以装载巨大的Dystrophin蛋白基因。对于研究者而言,将巨大的Dystrophin蛋白基因缩小后装载入AAV表达盒内是一种挑战。因此,期望获得截短的Dystrophin蛋白基因,其可稳定表达具有治疗活性的小型Dystrophin蛋白。
肌营养不良蛋白相关蛋白(Utrophin)作为Dystrophin的同源蛋白,也在肌肉中普遍表达,其具有与Dystrophin类似的功能和结构(Miura P,Jasmin B J.Utrophinupregulation for treating Duchenne or Becker muscular dystrophy:how close arewe?[J].Trends Mol Med,2006,12(3):122-9;Fairclough R J,Wood M J,Davies KE.Therapy for Duchenne muscular dystrophy:renewed optimism from geneticapproaches[J].Nat Rev Genet,2013,14(6):373-8)。研究表明,Utrophin表达的上调也对于肌营养不良症的治疗有重要作用,也可能作为肌营养不良症的一个治疗靶点(GuiraudS,Chen H,Burns D T等,Advances in genetic therapeutic strategies for Duchennemuscular dystrophy[J].Exp Physiol,2015,100(12):1458-67;Moorwood C,Khurana TS.Duchenne muscular dystrophy drug discovery-the application of utrophinpromoter activation screening[J].Expert Opin Drug Discov,2013,8(5):569-81;Ricotti V,Spinty S,Roper H等,Safety,Tolerability,and Pharmacokinetics of SMTC1100,a 2-Arylbenzoxazole Utrophin Modulator,following Single-and Multiple-Dose Administration to Pediatric Patients with Duchenne Muscular Dystrophy[J].PLoS One,2016,11(4):e0152840)。此外,有研究显示,通过小分子化合物或者microRNA对肌营养不良蛋白相关蛋白Utrophin的表达进行上调,可以缓解肌营养不良疾病的症状。
发明内容
为了解决上述技术问题,在第一方面,本公开提供一种重组杂合蛋白,其包括:全长人肌营养不良蛋白相关蛋白(Utrophin)的N端结构域、铰链H1、膜收缩蛋白样重复序列R1、膜收缩蛋白样重复序列R2、膜收缩蛋白样重复序列R3和铰链H2的前半部分;以及,全长人肌营养不良蛋白(Dystrophin)的膜收缩蛋白样重复序列R23、膜收缩蛋白样重复序列R24、铰链H4和CR结构域。
在一个实施方式中,上述重组杂合蛋白包含SEQ ID NO:4所示的氨基酸序列。在一个优选实施方式中,上述重组杂合蛋白的氨基酸序列如SEQ ID NO:4所示。
本公开的重组杂合蛋白可以有效地改善肌肉功能,缓解肌营养不良疾病的症状,对肌营养不良症具有良好的治疗效果。
在第二方面,本公开提供一种编码根据第一方面所述的重组杂合蛋白的核酸分子。
在一个实施方式中,上述核酸分子的核苷酸序列与SEQ ID NO:8或SEQ ID NO:10所示的核苷酸序列具有至少50%的同一性,优选具有至少50%、60%、70%、80%、85%、90%、95%、99%或100%的同一性。
在一个实施方式中,上述核酸分子包含SEQ ID NO:8或SEQ ID NO:10所示的核苷酸序列。在一个优选实施方式中,上述核酸分子的核苷酸序列如SEQ ID NO:8或SEQ ID NO:10所示。
在第三方面,本公开提供一种转基因表达盒,其包括:启动子、根据第二方面所述的核酸分子、mini polyA。
在一个实施方式中,启动子选自:CB启动子、CAG启动子、肌肉肌酸激酶MCK启动子、人肌酸激酶hCK启动子、截短的人肌酸激酶CK(Shortened CK,简称shCK)启动子、骨骼肌α-actin启动子、心肌α-actin启动子、肌球蛋白重链(MyHC)启动子、肌球蛋白轻链2(MLC2)启动子、肌球蛋白轻链3F启动子、结蛋白(desmin)基因启动子和生肌调控因子家族(MyoG、Myf5、Mrf4和Myogenin)等肌肉特异性基因的启动子。在一个优选实施方式中,启动子为hCK启动子或shCK启动子。在一个更优选实施方式中,启动子为shCK启动子。与hCK相比,使用shCK可获得更高的蛋白表达水平。
在一个实施方式中,启动子的核苷酸序列如SEQ ID NO:9所示。
在一个实施方式中,转基因表达盒还包括调控元件,例如位于两端的两个ITR,所述ITR为正常ITR或缩短ITR,例如145bp的正常ITR或100bp的缩短ITR。在一个优选实施方式中,所述两个ITR均为145bp的正常ITR。
在一个实施方式中,转基因表达盒还包括复制起点、聚腺苷酸化信号、内部核糖体进入位点(IRES)和/或2A信号,例如P2A、T2A和F2A。
在一个实施方式中,转基因表达盒的核苷酸序列如SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:6或SEQ ID NO:7所示。
在第四方面,本公开提供一种基因递送***,其包括:根据第三方面所述的转基因表达盒和AAV衣壳蛋白。
在一个实施方式中,上述AAV衣壳蛋白为天然AAV衣壳蛋白或人工改造的AAV衣壳蛋白。在一个优选实施方式中,上述AAV选自:AAV1、AAV2、AAV3、AAV4、AAV5、AAV6、AAV7、AAV8、AAV9、AAV10、AAV11,AAV12、AAV-DJ、AAV-DJ8、AAV-DJ9、AAVrh8、AAVrh8R、AAVrh10、AAVrh39、AAVrh43、AAV32.33、AAV3B、AAVv66、AAVXL32和AAV.PHP.B。
本公开的核酸分子、转基因表达盒和基因递送***可以在肌肉组织中稳定表达上述重组杂合蛋白,由此改善肌肉功能,实现对肌营养不良症的良好治疗效果。
在第五方面,本公开提供根据第三方面所述的转基因表达盒或根据第四方面所述的基因递送***在制备用于治疗肌营养不良症的药物中的应用。
在一个实施方式中,肌营养不良症包括:杜氏型肌营养不良症、贝克型肌营养不良症,以及其他肌肉退行性疾病。
在一个优选实施方式中,肌营养不良症为杜氏型肌营养不良症。
在第六方面,本公开提供一种药物,其包含:根据第一方面所述的重组杂合蛋白、根据第二方面所述的核酸分子、根据第三方面所述的转基因表达盒和根据第四方面所述的基因递送***中的一种,以及赋形剂。
在一个实施方式中,上述药物用于治疗肌营养不良症,所述肌营养不良症包括:杜氏型肌营养不良症、贝克型肌营养不良症,以及其他肌肉退行性疾病。在一个优选实施方式中,肌营养不良症为杜氏型肌营养不良症。
在第七方面,本公开提供一种治疗肌营养不良症的方法,包括向有需要的受试者施用治疗有效量的根据第六方面所述的药物。
在一个实施方式中,药物通过全身途径或局部途径施用,例如静脉内施用、肌内施用、皮下施用、经口施用、局部接触、腹膜内施用和病灶内施用。
在一个优选实施方式中,药物通过全身途径施用,例如静脉内施用。
在一个优选实施方式中,药物通过局部途径施用于肌肉,例如注射至肱二头肌或腓肠肌。
附图说明
图1A示出了全长人肌营养不良蛋白、全长人肌营养不良蛋白相关蛋白以及本发明人构建的M6构建体编码的重组杂合蛋白的结构(亚结构域)。
图1B示出了根据一个实施方式的hCK-opti-M6、hCK-M6、hCK-B84、shCK-opti-M6以及shCK-M6表达盒的示意图。
图2A是AAV9-hCK-opti-M6、AAV9-hCK-M6、AAV9-shCK-opti-M6、AAV9-shCK-M6注射小鼠6周后心脏中治疗性蛋白的免疫荧光分析。WT小鼠、Mdx小鼠及治疗组小鼠心脏的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图2B是AAV9-hCK-opti-M6、AAV9-hCK-M6、AAV9-shCK-opti-M6、AAV9-shCK-M6注射小鼠6周后腓肠肌中治疗性蛋白的免疫荧光分析。WT小鼠、Mdx小鼠及治疗组小鼠腓肠肌的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图2C是AAV9-hCK-opti-M6、AAV9-hCK-M6、AAV9-shCK-opti-M6、AAV9-shCK-M6注射小鼠6周后肱二头肌中治疗性蛋白的免疫荧光分析。WT小鼠、Mdx小鼠及治疗组小鼠肱二头肌的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图2D是AAV9-hCK-opti-M6、AAV9-hCK-M6、AAV9-shCK-opti-M6、AAV9-shCK-M6注射小鼠6周后横膈膜中治疗性蛋白的免疫荧光分析。WT小鼠、Mdx小鼠及治疗组小鼠横膈膜的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图3显示了opti-M6序列与现有B84序列在小鼠体内表达的对比。WT小鼠、Mdx小鼠、hCK-opti-M6及hCK-B84治疗组小鼠的心脏、腓肠肌和横膈膜的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图4A是AAV9-shCK-opti-M6和AAV9-hCK-B84注射小鼠4周后心脏中治疗性蛋白的免疫荧光分析。WT小鼠、Mdx小鼠及两个治疗组小鼠心脏的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图4B是AAV9-shCK-opti-M6和AAV9-hCK-B84注射小鼠4周后腓肠肌中治疗性蛋白的免疫荧光分析。WT小鼠、Mdx小鼠及两个治疗组小鼠腓肠肌的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图4C是AAV9-shCK-opti-M6和AAV9-hCK-B84注射小鼠4周后股四头肌中治疗性蛋白的免疫荧光分析。WT小鼠、Mdx小鼠及两个治疗组小鼠股四头肌的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图4D是AAV9-shCK-opti-M6和AAV9-hCK-B84注射小鼠4周后肱二头肌中治疗性蛋白的免疫荧光分析。WT小鼠、Mdx小鼠及两个治疗组小鼠肱二头肌的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图4E是AAV9-shCK-opti-M6和AAV9-hCK-B84注射小鼠4周后胫骨前肌中治疗性蛋白的免疫荧光分析。WT小鼠、Mdx小鼠及两个治疗组小鼠胫骨前肌的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图4F是AAV9-shCK-opti-M6和AAV9-hCK-B84注射小鼠4周后横膈膜中治疗性蛋白的免疫荧光分析。WT小鼠、Mdx小鼠及两个治疗组小鼠横膈膜的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图4G是AAV9-shCK-opti-M6和AAV9-hCK-B84注射小鼠4周后肋间肌中治疗性蛋白的免疫荧光分析。WT小鼠、Mdx小鼠及两个治疗组小鼠肋间肌的冰冻切片用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图4H显示了shCK-opti-M6表达盒与hCK-B84表达盒的表达水平。WT小鼠、Mdx小鼠、AAV9-shCK-opti-M6和AAV9-hCK-B84治疗4周后小鼠(a)心脏、(b)腓肠肌和(c)横膈膜的蛋白质印迹分析。GAPDH作为内参。
图5显示了雄性和雌性小鼠的血清CK水平。(A)是雄性WT小鼠、Mdx小鼠、AAV9-shCK-opti-M6和AAV9-hCK-B84治疗8-9周后血清CK水平,(B)是雌性WT小鼠、Mdx小鼠、AAV9-shCK-opti-M6和AAV9-hCK-B84治疗8-9周后血清CK水平。n=4,*p<0.05,**p<0.01,***p<0.001,t检验。
图6显示了小鼠肌肉功能和行为学改善的情况。WT小鼠、Mdx小鼠、AAV9-shCK-opti-M6和AAV9-hCK-B84治疗8周后小鼠的(A)转棒仪运动能力测试和(B)抓力测试。n=4,*p<0.05,**p<0.01,t检验。
图7A是AAV9-shCK-opti-M6在小鼠心脏中的长期表达。注射后的不同时间点(4周、6周、9周和12周)小鼠心脏中治疗性蛋白的免疫荧光分析,用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图7B是AAV9-shCK-opti-M6在小鼠腓肠肌中的长期表达。注射后的不同时间点(4周、6周、9周和12周)小鼠腓肠肌中治疗性蛋白的免疫荧光分析,用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图7C是AAV9-shCK-opti-M6在小鼠股四头肌中的长期表达。注射后的不同时间点(4周、6周、9周和12周)小鼠股四头肌中治疗性蛋白的免疫荧光分析,用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图7D是AAV9-shCK-opti-M6在小鼠肱二头肌中的长期表达。注射后的不同时间点(4周、6周、9周和12周)小鼠肱二头肌中治疗性蛋白的免疫荧光分析,用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图7E是AAV9-shCK-opti-M6在小鼠胫骨前肌中的长期表达。注射后的不同时间点(4周、6周、9周和12周)小鼠胫骨前肌中治疗性蛋白的免疫荧光分析,用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图7F是AAV9-shCK-opti-M6在小鼠横膈膜中的长期表达。注射后的不同时间点(4周、6周、9周和12周)小鼠横膈膜中治疗性蛋白的免疫荧光分析,用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图7G是AAV9-shCK-opti-M6在小鼠肋间肌中的长期表达。注射后的不同时间点(4周、6周、9周和12周)小鼠肋间肌中治疗性蛋白的免疫荧光分析,用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图7H是AAV9-shCK-opti-M6在小鼠舌中的长期表达。注射后的不同时间点(4周、6周、9周和12周)小鼠舌中治疗性蛋白的免疫荧光分析,用抗体进行免疫荧光染色,用DAPI复染细胞核,比例尺:200μm。
图7I显示了shCK-opti-M6表达盒在小鼠体内的长期表达水平。AAV9-shCK-opti-M6治疗4、6、9、12周后小鼠的(a)心脏、(b)腓肠肌、(c)股四头肌、(d)肱二头肌、(e)胫骨前肌、(f)横膈膜、(g)肋间肌和(h)舌的蛋白质印迹分析。GAPDH作为内参。
图8显示了重组杂合蛋白(即M6和opti-M6构建体蛋白产物)的氨基酸序列(SEQ IDNO:4)。
图9显示密码子优化的M6(opti-M6)构建体的核苷酸序列(SEQ ID NO:8)。
图10显示shCK启动子的核苷酸序列(SEQ ID NO:9)。
图11显示未经密码子优化的M6构建体的核苷酸序列(SEQ ID NO:10)。
具体实施方式
除非另有定义,否则本文使用的所有技术和科学术语具有与本公开所属领域的普通技术人员的通常理解相同的含义。
除非另有说明,否则本文列出的核酸或多核苷酸序列是单链形式,方向是从5'至3',从左至右。本文提供的核苷酸和氨基酸采用IUPACIUB生化命名委员会建议的格式,对于氨基酸采用单字母代码或三字母代码。
除非另有说明,“多核苷酸”是“核酸”的同义词,指任何长度的核苷酸的聚合形式,包括脱氧核糖核苷酸或核糖核苷酸,它们的混合序列或类似物。多核苷酸可以包括修饰的核苷酸,例如甲基化或限制的核苷酸和核苷酸类似物。
在本文中,术语“包含”、“具有”、“包括”和“含有”应被解释为开放式术语(即意味着“包括但不限于”)。
在本文中,术语“患者”和“受试者”可互换使用并且以其常规意义使用,指患有或容易患有可通过施用本公开的药物进行预防或治疗的病症的生物体,并且包括人和非人动物(例如,啮齿动物或其他哺乳动物)。
在一个实施方式中,受试者是非人动物(例如,黑猩猩和其他猿和猴物种;农场动物,如牛、绵羊、猪、山羊和马;家养哺乳动物,例如狗和猫;实验动物包括啮齿类动物,如小鼠、大鼠和豚鼠;禽类,包括家禽、野禽和猎禽,如鸡、火鸡和其他鸡类、鸭、鹅等)。在一个实施方式中,受试者是哺乳动物。在一个实施方式中,受试者是人。
在本文中,术语“治疗”包括:(1)抑制病状、疾病或者病症,即,阻止、减少或者延迟疾病的发展或其复发或者其至少一种临床或者亚临床症状的发展;或者(2)缓解疾病,即,引起病状、疾病或者病症或者其临床或者亚临床症状中的至少一种消退。
在本文中,术语“治疗有效量”指产生施用它要达到的治疗效果的剂量。例如,适用于治疗肌营养不良症的药物的治疗有效量可为能够预防或改善与该肌营养不良症相关的一种或多种症状的量。
在本文中,术语“改善”指与疾病有关的症状的改善,并且可以指至少一种衡量或定量该症状的参数的改善。
在本文中,术语“预防”病状、疾病或者病症包括:预防、延迟或者减少受试者中发展的病状、疾病或者病症的至少一种临床或者亚临床症状出现的发生率和/或可能性,该受试者可能患有或易患该病状、疾病或者病症但尚未经历或者表现出该病状、疾病或者病症的临床或亚临床症状。
在本文中,术语“局部施用”或“局部途径”是指具有局部作用的给药。
在本文中,术语“转导”、“转染”和“转化”是指将外源核酸递送到宿主细胞中,然后多核苷酸产物的转录和翻译的过程,该过程包括使用重组病毒将外源多核苷酸引入宿主细胞。
在本文中,术语“基因送递”指的是将外源多核苷酸引入细胞来进行基因传递,包括靶向、结合、摄取、转运、复制子整合和表达。
在本文中,术语“基因表达”或“表达”是指基因转录、翻译和翻译后修饰产生基因的RNA或蛋白产物的过程。
在本文中,术语“感染”是指包含多核苷酸组分的病毒或病毒颗粒将多核苷酸递送至细胞中并产生其RNA和蛋白质产物的过程,也可指病毒在宿主细胞中的复制过程。
在本文中,术语“靶向”是指病毒优先进入一些细胞或组织,然后进一步在细胞中表达病毒基因组或重组转基因携带的序列。
在本文中,术语“载体”指封装多核苷酸的一个或一系列大分子,其促进多核苷酸在体外或体内递送至靶细胞。载体的种类包括但不限于质粒、病毒载体、脂质体和其他基因递送载体。待递送的多核苷酸有时被称为“表达盒”或“转基因盒”,其可以包含但不限于某些蛋白质或合成多肽(其可以增强、抑制、削弱、保护、触发或预防某些生物学和生理功能)的编码序列、疫苗开发中感兴趣的编码序列(例如表达适于在哺乳动物中引发免疫应答的蛋白质、多肽或肽的多核苷酸)、RNAi材料的编码序列(例如,shRNA、siRNA、反义寡核苷酸)或可选的生物标记。
在本文中,术语“表达盒”、“转基因盒”和“转基因表达盒”可互换地使用,指编码特定蛋白质、多肽或RNAi元件的多核苷酸片段,其可以克隆到质粒载体中。
在一些实施方式中,“盒”也可以包装到AAV颗粒中并用作病毒基因组以将转基因产物递送到靶细胞中。“盒”还可以包括其他调控元件,例如特异性启动子/增强子、polyA、调控内含子等,以增强或减弱转基因产物的表达。
在一个实施方式中,除了编码蛋白质产物的序列外,转基因盒还包含许多调控元件以使转基因包装到病毒中,例如145bp的正常ITR、长度大约100bp的缩短ITR。在一些实施方式中,转基因盒还包含用于控制蛋白质产物表达的多核苷酸元件,例如复制起点、聚腺苷酸化信号、内部核糖体进入位点(IRES)或2A信号(例如P2A、T2A、F2A)、启动子和增强子,例如,具有脊椎动物β-肌动蛋白、β-球蛋白或β-球蛋白调节元件的CMV启动子或其他杂种CMV启动子(称为CB和CAG启动子)、肌肉肌酸激酶MCK启动子、人肌酸激酶hCK启动子、截短的肌酸激酶shCK启动子、骨骼肌α-actin启动子、心肌α-actin启动子、肌球蛋白重链(MyHC)启动子、肌球蛋白轻链2(MLC2)启动子、肌球蛋白轻链3F启动子、结蛋白(desmin)基因启动子和生肌调控因子家族(MyoG、Myf5、Mrf4和Myogenin)等肌肉特异性基因的启动子。启动子和增强子可以被化学药品或激素(例如强力霉素或他莫昔芬)激活,以确保在特定时间点的进行基因表达。此外,启动子和增强子可以是天然或人工或嵌合序列,即原核或真核序列。
在一些优选实施方式中,用于基因表达的诱导型调控元件可以是组织或器官特异性启动子或增强子,其包括但不限于:对各种类型的肌肉细胞具有特异性的启动子,例如,肌肉肌酸激酶MCK启动子、人肌酸激酶hCK启动子、截短的肌酸激酶shCK启动子、骨骼肌α-actin启动子、心肌α-actin启动子、肌球蛋白重链(MyHC)启动子、肌球蛋白轻链2(MLC2)启动子、肌球蛋白轻链3F启动子、结蛋白(Desmin)基因启动子和生肌调控因子家族(MyoG、Myf5、Mrf4和Myogenin)等肌肉特异性基因的启动子;以及成骨细胞谱系的特异性启动子(例如骨钙蛋白启动子)。
在本文中,术语“反向末端重复(ITR)”包括形成发夹结构并用作顺式元件以介导病毒复制、包装和整合的任何AAV病毒末端重复或合成序列。本文的ITR包括但不限于来自1-12型AAV(禽类AAV、牛AAV、犬AAV、马AAV和绵羊AAV的末端重复序列)。此外,AAV末端重复序列不必具有天然末端重复序列,只要该末端重复序列可用于病毒复制、包装和整合即可。
在本文中,术语“顺式元件”是指包装在AAV颗粒中并在靶细胞中表达以产生具有治疗作用的蛋白质产物的转基因盒。
如图1A所示,全长人肌营养不良蛋白包括四个结构域:N端结构域、中心杆结构域、CR结构域和C端(CT)结构域,其中,中心杆结构域包括24个膜收缩蛋白样重复序列(R1-R24)和4个铰链(H1-H4)。全长人肌营养不良蛋白相关蛋白同样包括四个结构域:N端结构域、中心杆结构域、CR结构域和C端(CT)结构域,其中,中心杆结构域包括22个膜收缩蛋白样重复序列(R1-R22)和4个铰链(H1-H4)。它们的具体氨基酸序列在本领域内是已知的,可以在文献或在公共数据库查找,例如UniProt蛋白质数据库。
本公开的M6构建体包含两种形式:未经密码子优化的M6构建体以及经密码子优化的M6(opti-M6)构建体。
在本文中,术语“密码子优化”是指从其天然形式修饰的多核苷酸序列。这样的修饰导致一个或多个碱基对的差异,其相应的氨基酸序列中有或没有改变,可能增强或抑制基因的表达和/或对修饰的多核苷酸序列的细胞应答。
在一个实施方式中,AAV衣壳蛋白可以为任何AAV血清型衣壳蛋白,包括天然AAV衣壳蛋白(例如,天然的1-11型AAV、禽AAV、牛AAV、犬AAV、马AAV和绵羊AAV的衣壳蛋白)和其他人工改造的AAV衣壳蛋白(例如,人工改造的1-11型AAV、禽AAV、牛AAV、犬AAV、马AAV和绵羊AAV的衣壳蛋白)。不同AAV血清型的基因组序列、ITR序列、Rep和Cap蛋白在本领域内是已知的。这些序列可以在文献或在公共数据库查找,例如GenBank数据库和/或WO 2021050970A1;US 2019/036676 A1;Choudhury SR等,In Vivo Selection Yields AAV-B1 Capsidfor Central Nervous System and Muscle Gene Therapy.Mol Ther.,2016,24(7):1247-57;Hsu HL.等,Structural characterization of a novel human adeno-associatedvirus capsid with neurotropic properties.Nat Commun 11,3279(2020)。
在一个实施方式中,本公开提供了具有改善肌肉功能作用的治疗工具,可以用于治疗具有相关病理机制的多种疾病,包括但不限于:杜氏型肌营养不良症、贝克型肌营养不良症,以及其他肌肉退行性疾病。
在一个实施方式中,肌肉退行性疾病的临床表现包括肌肉萎缩和/或运动能力降低或丧失。
在一个实施方式中,治疗工具(例如转基因表达盒)的蛋白产物包括具有改善肌肉功能作用的蛋白质,例如但不限于,Dystrophin(全长的或截短的)、Utrophin(全长的或截短的)及两者的杂合组合。
在一个实施方式中,治疗工具为蛋白质,例如但不限于,Dystrophin(全长的或截短的)、Utrophin(全长的或截短的)及两者的重组杂合蛋白。
在一个实施方式中,本公开的转基因表达盒包括:hCK启动子序列(SEQ ID NO:1)、mini聚腺苷酸化(polyA)序列(SEQ ID NO:2)和密码子优化的M6(opti-M6)构建体(SEQ IDNO:8),如此形成hCK-opti-M6表达盒(SEQ ID NO:3)。hCK-opti-M6表达盒的两侧是145bp的正常ITR,其可使表达盒作为单链AAV载体包装到AAV病毒颗粒中。
在一个实施方式中,本公开的转基因表达盒包括:hCK启动子序列(SEQ ID NO:1)、mini聚腺苷酸化(polyA)序列(SEQ ID NO:2)和未经密码子优化的M6构建体(SEQ ID NO:10),如此形成hCK-M6表达盒(SEQ ID NO:5)。hCK-M6表达盒的两侧是145bp的正常ITR,其可使表达盒作为单链AAV载体包装到AAV病毒颗粒中。
在一个实施方式中,本公开的转基因表达盒包括:shCK启动子序列(SEQ ID NO:9)、mini聚腺苷酸化(polyA)序列(SEQ ID NO:2)和密码子优化的M6(opti-M6)构建体(SEQID NO:8),如此形成shCK-opti-M6表达盒(SEQ ID NO:6)。shCK-opti-M6表达盒的两侧是145bp的正常ITR,其可使表达盒作为单链AAV载体包装到AAV病毒颗粒中。
在一个实施方式中,本公开的转基因表达盒包括:shCK启动子序列(SEQ ID NO:9)、mini聚腺苷酸化(polyA)序列(SEQ ID NO:2)和未经密码子优化的M6构建体(SEQ IDNO:10),如此形成shCK-M6表达盒(SEQ ID NO:7)。shCK-M6表达盒的两侧是145bp的正常ITR,其可使表达盒作为单链AAV载体包装到AAV病毒颗粒中。
在一些实施方式中,通过HEK293细胞的三质粒(质粒1:顺式元件质粒;质粒2:AAVRep/Cap质粒;质粒3:辅助质粒)转染来生产肌营养不良蛋白及相关蛋白AAV颗粒。
在一个实施方式中,为了产生具有治疗功能的AAV颗粒,按如下进行HEK293细胞的三质粒转染:质粒1:具有ITR的顺式元件质粒(例如,hCK-opti-M6、hCK-M6、shCK-opti-M6和shCK-M6表达盒);质粒2:具有衣壳蛋白(例如,AAV9衣壳蛋白)编码序列的AAV Rep/Cap质粒;质粒3:具有腺病毒成分的辅助质粒,其能够促进AAV病毒体的复制、组装和包装。在一个实施方式中,将HEK293细胞产生的AAV颗粒通过氯化铯(CsCl)密度梯度离心进行纯化(例如本公开实施例2所述的方法)。
本领域技术人员可以使用已知的标准方法来生产重组和合成的多肽或蛋白质、设计核酸序列、生产转化细胞、构建重组AAV突变体、改造衣壳蛋白质、包装表达AAV Rep和/或Cap序列的载体,以及瞬时或稳定转染包装细胞。这些技术是本领域技术人员已知的。参见例如,分子克隆(MOLECULAR CLONING):实验室手册(A LABORATORY MANUAL),第二版,(冷泉港,纽约州,1989年)。
在一些实施方式中,本公开的基因递送***用于辅助细胞移植治疗。具体地,具有转基因的AAV颗粒可用于体外转导各种类型的细胞以产生表达蛋白质产物的稳定细胞系,然后可将其体内引入以用于治疗目的。细胞的类型包括但不限于内皮细胞、成肌细胞、成纤维细胞、星形胶质细胞、Müller细胞、少突胶质细胞、小胶质细胞、杆状细胞和视锥细胞、神经元、造血干细胞、单核细胞、粒细胞、淋巴细胞、破骨细胞和巨噬细胞。
在一个实施方式中,用于移植的细胞是受试者的自体细胞,其允许体外培养。将细胞引入或移植到受试者中的原理和技术是本领域技术人员已知的。
在一个实施方式中,从HEK293细胞的培养基和裂解物中收获AAV颗粒。纯化方法例如亲和色谱、离子交换色谱、氯化铯和碘克沙醇梯度超速离心。与AAV生产和纯化有关的化学物质或试剂包括但不限于:用于细胞培养的化学物质或试剂(例如,细胞培养基的成分,包括牛、马、山羊、鸡或其他脊椎动物血清、谷氨酰胺、葡萄糖、蔗糖、丙酮酸纳、酚红;抗生素,例如青霉素、卡那霉素、链霉素、四环素);用于细胞裂解、多核苷酸沉淀或超速离心的化学物质或试剂(例如Triton X-100、NP-40、脱氧胆酸钠、十二烷基硫酸钠、溴化多米芬、钠十二烷基水杨酸酯、氯化钠、氯化镁、氯化钙、氯化钡、硝酸盐、氯化钾、氯化铵、过硫酸铵、硫酸铵、PEG-20、PEG-40、PEG-400、PEG-2000、PEG-6000、PEG-8000、PEG-20000、Tris-HCl、Tris-乙酸盐、氯化锰、磷酸盐、碳酸氢盐、氯化铯、甲醇、乙醇、甘油、碘克沙醇、异丙醇、丁醇、安息香酶、DNase I、RNase);亲和柱材料(例如AAVX亲和树脂、硫酸肝素蛋白聚糖和粘蛋白树脂、与AAV特异性抗体相关的其他材料);离子交换色谱材料和洗涤缓冲液中包含的酸、碱和有机物(例如盐酸、硫酸、乙酸、甲酸、硝酸、尿素、丙酮、氯仿、乙腈、三氟乙酸、氢氧化钠、氢氧化钾、氢氧化钡、氢氧化铵、Tris碱或其他有机胺、泊洛沙姆188、吐温20、吐温40、吐温80、盐酸胍)。
在一个实施方式中,由AAV载体递送到靶细胞的外源多核苷酸编码用于治疗用途的天然蛋白质,所述天然蛋白质经密码子优化或未经密码子优化。
在一个实施方式中,由AAV载体递送到靶细胞的外源多核苷酸编码合成多肽。
在一个实施方式中,本公开的转基因表达盒或基因递送***被制成药物制剂(例如,注射剂、片剂、胶囊剂、散剂、滴眼剂)施用于人或其他哺乳动物。该药物制剂还包含其他成分,例如药物辅料、水溶性或有机溶剂(例如水、甘油、乙醇、甲醇、异丙醇、氯仿、苯酚或聚乙二醇)、盐(例如氯化钠、氯化钾、磷酸盐、乙酸盐、碳酸氢盐、Tris-HCl和Tris-乙酸盐)、延缓溶解试剂(例如石蜡)、表面活性剂、抗微生物剂、脂质体、脂质复合物、免疫抑制剂(例如可的松、***、环孢霉素)、非甾体抗炎药(NSAID,例如阿司匹林、布洛芬、对乙酰氨基酚)微球、硬质基质、半固体载体、纳米球或纳米颗粒。此外,药物制剂可以通过吸入、全身或局部(例如,静脉内、皮下、眼内、玻璃体内、视网膜下、脉络膜上、肠胃外、肌内、脑室内、口服、腹膜内和鞘内)的给药方式以单剂量或多剂量递送。
在一个实施方式中,本公开提供了一种药物,其包含本公开的重组杂合蛋白、核酸分子、转基因表达盒或基因递送***;以及赋形剂。本公开的药物可用于体外转导细胞或体内转导哺乳动物(例如啮齿动物、灵长类动物和人类),从而治疗各种与肌肉功能缺陷相关的疾病,例如肌营养不良症,包括:杜氏型肌营养不良症、贝克型肌营养不良症,以及其他肌肉退行性疾病。在一个实施方式中,肌营养不良症为杜氏肌营养不良症。
在一个实施方式中,治疗肌营养不良症是指改善接受治疗的患者的肌肉损伤程度、肌酸激酶水平以及NASS(The North American Spine Society)肌肉功能得分。
下面结合附图和实施例对本公开作进一步详细的说明。以下实施例仅用于说明本公开而不用于限制本公开的范围。实施例中未注明具体条件的实验方法,系按照本领域已知的常规条件,或按照制造厂商所建议的条件进行操作。
实施例
实施例1:M6和opti-M6构建体以及AAV载体的设计及构建
利用人肌营养不良蛋白的cDNA作为模板通过PCR克隆方法得到B84(Mini-dystrophin)构建体(SEQ ID NO:11)。B84构建体及其编码的小型人肌营养不良蛋白质可参见例如CN 109641944A(分别对应于Hopti-Dys3978和Dys3978)或Wang B,Li J,XiaoX.Adeno-associated virus vector carrying human minidystrophin geneseffectively ameliorates muscular dystrophy in mdx mouse model[J].Proc NatlAcad Sci U S A,2000,97(25):13714-9。
通过大量实验研究以及合理设计,本发明人还基于全长人肌营养不良蛋白和全长人肌营养不良蛋白相关蛋白构建了高度截短的M6构建体(SEQ ID NO:10),并在该M6构建体的基础上进行密码子优化得到了opti-M6构建体(SEQ ID NO:8)。如图1A所示,M6构建体或opti-M6构建体编码的重组杂合蛋白包含:全长人肌营养不良蛋白相关蛋白的N端结构域、铰链1(H1)、膜收缩蛋白样重复序列1(R1)、膜收缩蛋白样重复序列2(R2)、膜收缩蛋白样重复序列3(R3)和铰链2(H2)的前半部分;以及,全长人肌营养不良蛋白的膜收缩蛋白样重复序列23(R23)、膜收缩蛋白样重复序列24(R24)、铰链4(H4)和CR结构域。
此外,为了提高目标蛋白质的表达,本发明人还基于人肌酸激酶hCK启动子(SEQID NO:1)构建了截短的人肌酸激酶CK(shCK)启动子。
然后,将上述M6及opti-M6基因亚克隆到AAV载体质粒中,分别采用hCK启动子以及shCK启动子,产生载体AAV-hCK-M6-polyA、AAV-hCK-opti-M6-polyA、AAV-shCK-M6-polyA和AAV-shCK-opti-M6-polyA。同样地,将B84基因克隆到含有hCK启动子和mini polyA信号序列的AAV载体质粒中,产生载体AAV-hCK-B84。
实施例2:M6和opti-M6构建体在Mdx小鼠体内的表达
为了研究M6和opti-M6构建体在小鼠体内的表达,本实施例中设置4个治疗组:hCK-opti-M6、hCK-M6、shCK-opti-M6和shCK-M6。
将实施例1中构建的载体AAV-hCK-M6-polyA、AAV-hCK-opti-M6-polyA、AAV-shCK-M6-polyA和AAV-shCK-opti-M6-polyA包装成AAV9病毒颗粒。AAV病毒是根据三质粒共转染方法生产的(如Xiao X,Li J,Samulski R J.Production of high-titer recombinantadeno-associated virus vectors in the absence of helper adenovirus[J].JVirol,1998,72(3):2224-32所述),通过三质粒转染上述4个新型载体顺式元件质粒、AAV9衣壳质粒和腺病毒辅助质粒。转染40-80小时后裂解HEK293细胞,然后除去多核苷酸。随后使用Snyder R,Xiao S,Samulski R J.Production of recombinant adeno-associatedviral vectors[J],1996所述的方案,通过CsCl密度梯度超速离心对AAV病毒载体进行了两次纯化。通过qPCR方法测定的病毒滴度约为2×1013~1×1014vg/ml。通过SDS-PAGE检测衣壳蛋白纯度。通过凝胶法检测内毒素,结果为合格。
然后,通过尾静脉向Mdx小鼠体内分别注射3×1013vg/kg的上述AAV颗粒。以同龄WT小鼠和同窝Mdx小鼠作为对照。注射后6周,将小鼠解剖。收集心脏、腓肠肌、肱二头肌和横膈膜组织,进行冰冻切片和免疫荧光染色。免疫荧光染色使用的兔源多克隆抗体购自Abcam公司(货号ab251754),其可识别人肌营养不良蛋白第2800-3000位的氨基酸片段(膜收缩蛋白样重复序列R23和R24)。因此,B84和M6构建体表达的蛋白质均可被该抗体识别。
心脏、腓肠肌、肱二头肌和横膈膜组织的免疫荧光染色可分别反映与Mdx小鼠心脏功能、下肢运动功能、上肢运动功能及呼吸功能相关的肌肉病理改善情况。Mdx小鼠的病理表型开始于3周龄左右,伴随着肌纤维的变性再生,细胞核位于肌纤维的中央是这一过程的特征表现,也是主要的病理表现。
结果显示,在治疗后6周的Mdx小鼠的心脏中,4个治疗组的蛋白表达水平均显著高于未治疗的Mdx对照组,其中,hCK-opti-M6和shCK-opti-M6表达盒的表达水平高于hCK-M6和shCK-M6表达盒(图2A)。同样,治疗后小鼠的腓肠肌中也观察到杂合的治疗性蛋白的表达,opti-M6表达水平显著高于未优化的M6(图2B)。在肱二头肌中,4个治疗组的蛋白表达水平均显著高于未治疗的Mdx对照组,且shCK-opti-M6显著优于其他3个治疗组,表达水平接近WT小鼠,明显纠正了Mdx小鼠骨骼肌中央成核现象(图2C)。在横膈膜中的表达情况与肱二头肌相似,shCK-opti-M6在视野中广泛表达,强于其他3个表达盒(图2D)。
上述结果表明,M6和opti-M6构建体可在心脏、腓肠肌等4个代表性的肌肉组织中广泛表达杂合的治疗性蛋白,产生治疗效果。与M6构建体相比,优化后的opti-M6构建体的表达水平更高。并且,与hCK相比,使用shCK可获得更高的蛋白表达水平。综上,shCK-opti-M6表达盒的体内活性最佳。
实施例3:opti-M6构建体与B84构建体在Mdx小鼠体内的表达
在本实施例中,发明人比较了opti-M6构建体与B84构建体在模型小鼠体内的表达水平。分别将opti-M6与B84构建到原有hCK启动子的载体中并包装成病毒,得到AAV9-hCK-opti-M6和AAV9-hCK-B84病毒颗粒。通过尾静脉注射病毒颗粒治疗Mdx小鼠,注射剂量为3×1013vg/kg。以同龄WT小鼠和同窝Mdx小鼠作为对照。治疗6周后解剖小鼠,收集心脏、腓肠肌和横膈膜等组织。通过组织免疫荧光法检测不同组织中治疗性蛋白的表达。
结果显示,AAV9-hCK-opti-M6和AAV9-hCK-B84治疗后小鼠的心脏、腓肠肌和横膈膜中治疗性蛋白的表达水平均显著高于未治疗的mdx对照组(图3)。
如图3所示,在心脏中,AAV9-hCK-opti-M6治疗组达到与AAV9-hCK-B84治疗组相近的荧光强度,且AAV9-hCK-opti-M6治疗组的阳性细胞数更多;在腓肠肌中,AAV9-hCK-opti-M6治疗组的荧光强度明显强于AAV9-hCK-B84治疗组;在横膈膜中,与AAV9-hCK-B84治疗组相比,AAV9-hCK-opti-M6治疗组的荧光更强,且阳性细胞数明显更多。
综合来看,opti-M6构建体与B84构建体相比可产生更好的治疗效果。
实施例4:shCK-opti-M6载体与hCK-B84载体在Mdx小鼠体内的表达
在本实施例中,发明人比较了shCK-opti-M6载体与hCK-B84载体在模型小鼠体内的表达能力。
如实施例2中所述,将AAV-shCK-opti-M6和AAV-hCK-B84载体分别包装成AAV9-shCK-opti-M6和AAV9-hCK-B84病毒颗粒。通过尾静脉注射病毒颗粒以治疗Mdx小鼠,注射剂量为3×1013vg/kg。以同龄WT小鼠和同窝Mdx小鼠作为对照。治疗4周后解剖小鼠,收集心脏、腓肠肌、股四头肌、横膈膜等组织。然后,用免疫荧光法和蛋白质印迹法检测不同组织中的蛋白表达。
如图4A所示,AAV9-shCK-opti-M6和AAV9-hCK-B84治疗后小鼠心脏的治疗性蛋白表达水平显著高于未治疗的Mdx对照组,其中AAV9-shCK-opti-M6的荧光更强。
如图4B-4E所示,在四肢肌肉组织(腓肠肌、胫骨前肌、肱二头肌和股四头肌)中,AAV9-shCK-opti-M6和AAV9-hCK-B84治疗后也可观察到广泛的治疗性蛋白的表达。shCK-opti-M6治疗组在四肢肌肉组织中的表达水平显著高于hCK-B84治疗组。在shCK-opti-M6治疗组小鼠中,发明人在蛋白广泛表达的区域中观察到了肌纤维的外周成核,在一定程度上纠正了中央成核的病理表型,防止肌肉变性和再生,表明该载体治疗后可以改善肌肉病理表型。
如图4F-4H所示,在呼吸功能相关的横膈膜和肋间肌组织中,shCK-opti-M6和hCK-B84治疗组均观察到了广泛的治疗性蛋白的表达,两者的荧光强度没有显著差异。
用可识别人肌营养不良蛋白的膜收缩蛋白样重复序列R23和R24片段的抗体同时检测shCK-opti-M6和hCK-B84在体内的蛋白表达。蛋白质印迹结果显示,shCK-opti-M6在小鼠心脏中表达高于hCK-B84,shCK-opti-M6在腓肠肌和横膈膜中的表达水平与hCK-B84接近(图4G)。
综合上述结果表明,shCK-opti-M6与hCK-B84相比在表达上具有显著优势。
实施例5:shCK-opti-M6载体与hCK-B84载体治疗后Mdx小鼠的肌酸激酶水平
在本实施例中,为了验证shCK-opti-M6和hCK-B84载体在Mdx小鼠体内的治疗效果,发明人检测了血清肌酸激酶(Creatine Kinase,CK)水平,这是Mdx小鼠肌肉损伤的重要指标。
本实施例中共设置2个治疗组,分别为AAV9-shCK-opti-M6和AAV9-hCK-B84。通过尾静脉注射治疗Mdx小鼠,注射剂量为3×1013vg/kg。以同龄WT小鼠和同窝Mdx小鼠作为对照。每组8只,雌雄各4只。治疗8-9周后通过眼眶采血,收集血清,检测小鼠血清中的CK水平。
如图5所示,未经治疗的Mdx小鼠在4月龄时,血清CK水平较WT小鼠明显升高(雄性,**p<0.01;雌性,***p<0.001),而在经过AAV治疗的Mdx小鼠中显著降低,其中shCK-opti-M6治疗组的血清CK值显著下降(雄性,*p<0.05;雌性,***p<0.001)。
由此可见,shCK-opti-M6载体治疗后Mdx小鼠的肌酸激酶水平与hCK-B84载体相比更低,表明其具有更好的治疗效果。
实施例6:shCK-opti-M6和hCK-B84载体对Mdx小鼠运动能力和肌肉力量的影响
在本实施例中,为了评估shCK-opti-M6和hCK-B84载体对Mdx小鼠运动能力和肌肉力量的影响,对小鼠进行了转棒测试(运动)和抓力测试(力量)。
在WT小鼠、未治疗的Mdx小鼠、shCK-opti-M6和hCK-B84治疗8周后的Mdx小鼠(n=4)中进行了三次重复转棒试验。结果如图6A所示,未治疗Mdx小鼠与WT小鼠在转棒上的运动时间存在显著差异(*p<0.05)。与未治疗的Mdx小鼠相比,shCK-opti-M6载体治疗的Mdx小鼠的运动表现有显著改善(*p<0.05),hCK-B84载体治疗的Mdx小鼠无统计学差异。值得注意的是,shCK-opti-M6载体治疗的Mdx小鼠显示出接近WT小鼠的运动时间。
同时,小鼠抓力测试的结果显示,与未治疗的Mdx小鼠相比,shCK-opti-M6载体治疗的Mdx小鼠四肢的抓力有显著改善(**p<0.01),接近WT水平(图6B)。
上述结果表明,与hCK-B84载体相比,shCK-opti-M6载体能更有效地改善小鼠的肌肉功能和行为学表现。
实施例7:shCK-opti-M6载体在Mdx小鼠体内的长期表达
在本实施例中,发明人研究了shCK-opti-M6载体在Mdx小鼠体内的长期表达。通过尾静脉注射4组Mdx小鼠,注射剂量为3×1013vg/kg。分别在载体注射后的不同时间点(4周、6周、9周和12周)收集肌肉样本用于免疫荧光和蛋白质免疫印迹检测。以同龄WT小鼠和同窝Mdx小鼠作为对照。
结果显示,shCK-opti-M6载体治疗4周后,在心脏中就可以观察到蛋白的表达。在注射后6-9周,表达进入高峰期,阳性细胞数和荧光强度显著提高(图7A)。在shCK-opti-M6载体治疗6周后,在mdx小鼠的腓肠肌中观察到了广泛的蛋白表达(图7B)。在shCK-opti-M6载体治疗4周后,在股四头肌中观察到了较弱的荧光强度,荧光表达在注射后6-9周进入高峰期,且一直稳定持续到注射后12周(图7C)。肱二头肌免疫荧光染色结果与股四头肌类似(图7D)。在Mdx小鼠的胫骨前肌中,在注射后4周已显示出高水平的蛋白表达,在注射后6-9周表达水平进一步升高,且可持续到注射后12周(图7E)。横膈膜免疫荧光的染色结果与胫骨前肌类似(图7F)。肋间肌的免疫荧光染色结果显示,在shCK-opti-M6载体治疗后第4至9周均检测到了蛋白的高水平表达,在注射后12周表达略有下降(图7G)。舌的免疫荧光结果与肋间肌类似(图7H)。
用可识别人肌营养不良蛋白的膜收缩蛋白样重复序列R23和R24片段的抗体检测蛋白的表达,蛋白质印迹分析结果如图7I所示。心脏中,在注射后4周即可检测到蛋白表达,在6-9周表达水平最高,且一直持续到注射后12周。腓肠肌中,在注射后6周有较高的表达,在注射后12周表达达到高峰。股四头肌中,在注射后9周蛋白表达进入高峰期,且在注射后12周仍然保持高水平表达。肱二头肌中,在注射后6周蛋白的表达水平最高,注射后12周仍可检测到较高水平的表达。胫骨前肌中,在注射后4周即可检测到一定水平的蛋白表达,注射后6-9周表达一直保持在较高水平。横膈膜中,在注射后12周仍可检测到蛋白的表达。肋间肌蛋白质印迹分析的结果与舌头类似,均在注射后4-9周检测到了不同程度的蛋白表达,注射后12周表达水平有所下降。
上述免疫荧光和蛋白质免疫印迹结果表明,shCK-opti-M6可以实现在Mdx模型小鼠体内的长期稳定表达。
虽然通过参照本公开的某些优选实施方式,已经对本公开进行了图示和描述,但本领域的普通技术人员应该明白,以上内容是结合具体的实施方式对本公开所作的进一步详细说明,不能认定本公开的具体实施只局限于这些说明。本领域技术人员可以在形式上和细节上对其作各种改变,包括做出若干简单推演或替换,而不偏离本公开的精神和范围。
序列表
<110> 上海勉亦生物科技有限公司
<120> 用于治疗肌营养不良症的转基因表达盒
<130> PCNCNN21E014G
<160> 13
<170> PatentIn version 3.5
<210> 1
<211> 606
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> hCK启动子的核苷酸序列
<400> 1
gaattcggta ccccactacg ggtttaggct gcccatgtaa ggaggcaagg cctggggaca 60
cccgagatgc ctggttataa ttaacccaga catgtggctg cccccccccc ccccaacacc 120
tgctgcctct aaaaataacc ctgtccctgg tggatcccct gcatgcgaag atcttcgaac 180
aaggctgtgg gggactgagg gcaggctgta acaggcttgg gggccagggc ttatacgtgc 240
ctgggactcc caaagtatta ctgttccatg ttcccggcga agggccagct gtcccccgcc 300
agctagactc agcacttagt ttaggaacca gtgagcaagt cagcccttgg ggcagcccat 360
acaaggccat ggggctgggc aagctgcacg cctgggtccg gggtgggcac ggtgcccggg 420
caacgagctg aaagctcatc tgctctcagg ggcccctccc tggggacagc ccctcctggc 480
tagtcacacc ctgtaggctc ctctatataa cccaggggca caggggctgc cctcattcta 540
ccaccacctc cacagcacag acagacactc aggagccagc cagcgtcgag cggccgatcc 600
gccacc 606
<210> 2
<211> 54
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> mini POLYA的核苷酸序列
<400> 2
aggcctaata aagagctcag atgcatcgat cagagtgtgt tggttttttg tgtg 54
<210> 3
<211> 8667
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> hCK-opti-M6表达盒的核苷酸序列
<400> 3
ctagaggtcc ccagcgacct tgacgagcat ctgcccggca tttctgacag ctttgtgaac 60
tgggtggccg agaaggaatg ggagttgccg ccagattctg acatggatct gaatctgatt 120
gagcaggcac ccctgaccgt ggccgagaag ctgcatcgct ggcgtaatag cgaagaggcc 180
cgcaccgatc gcccttccca acagttgcgc agcctgaatg gcgaatggcg attccgttgc 240
aatggctggc ggtaatattg ttctggatat taccagcaag gccgatagtt tgagttcttc 300
tactcaggca agtgatgtta ttactaatca aagaagtatt gcgacaacgg ttaatttgcg 360
tgatggacag actcttttac tcggtggcct cactgattat aaaaacactt ctcaggattc 420
tggcgtaccg ttcctgtcta aaatcccttt aatcggcctc ctgtttagct cccgctctga 480
ttctaacgag gaaagcacgt tatacgtgct cgtcaaagca accatagtac gcgccctgta 540
gcggcgcatt aagcgcggcg ggtgtggtgg ttacgcgcag cgtgaccgct acacttgcca 600
gcgccctagc gcccgctcct ttcgctttct tcccttcctt tctcgccacg ttcgccggct 660
ttccccgtca agctctaaat cgggggctcc ctttagggtt ccgatttagt gctttacggc 720
acctcgaccc caaaaaactt gattagggtg atggttcacg tagtgggcca tcgccctgat 780
agacggtttt tcgccctttg acgttggagt ccacgttctt aatagtggac tcttgttcca 840
aactggaaca acactcaacc ctatctcggt ctattctttt gatttataag ggattttgcc 900
gatttcggcc tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattttaa 960
caaaatatta acgcttacaa tttaaatatt tgcttataca atcttcctgt ttttggggct 1020
tttctgatta tcaaccgggg tacatatgat tgacatgcta gttttacgat taccgttcat 1080
cgcctgcagg gggggggggg ggggggttgg ccactccctc tctgcgcgct cgctcgctca 1140
ctgaggccgg gcgaccaaag gtcgcccgac gcccgggctt tgcccgggcg gcctcagtga 1200
gcgagcgagc gcgcagagag ggagtggcca actccatcac taggggttcc tagatctgaa 1260
ttcggtaccc cactacgggt ttaggctgcc catgtaagga ggcaaggcct ggggacaccc 1320
gagatgcctg gttataatta acccagacat gtggctgccc cccccccccc caacacctgc 1380
tgcctctaaa aataaccctg tccctggtgg atcccctgca tgcgaagatc ttcgaacaag 1440
gctgtggggg actgagggca ggctgtaaca ggcttggggg ccagggctta tacgtgcctg 1500
ggactcccaa agtattactg ttccatgttc ccggcgaagg gccagctgtc ccccgccagc 1560
tagactcagc acttagttta ggaaccagtg agcaagtcag cccttggggc agcccataca 1620
aggccatggg gctgggcaag ctgcacgcct gggtccgggg tgggcacggt gcccgggcaa 1680
cgagctgaaa gctcatctgc tctcaggggc ccctccctgg ggacagcccc tcctggctag 1740
tcacaccctg taggctcctc tatataaccc aggggcacag gggctgccct cattctacca 1800
ccacctccac agcacagaca gacactcagg agccagccag cgtcgagcgg ccgatccgcc 1860
accgccacca tggccaaata tggggagcat gaggcctctc cagacaatgg ccagaatgag 1920
ttctctgaca tcatcaagag cagatctgat gagcacaatg atgtgcagaa gaaaaccttc 1980
accaagtgga tcaatgccag gttcagcaag tctggcaagc ctcctatcaa tgacatgttc 2040
acagacctga aggatggcag aaagctgctg gacctgctgg aaggcctgac aggcacaagc 2100
ctgcctaaag aaaggggcag caccagagtg catgccctga acaatgtgaa cagagtgctg 2160
caggtcctgc accagaacaa tgttgagctg gtcaatattg gaggcacaga cattgtggat 2220
ggcaaccaca agctgaccct gggcctgctg tggtccatca tcctgcactg gcaagtgaaa 2280
gatgtgatga aggatgtcat gtctgacctc cagcagacca actctgagaa gatcctgctg 2340
agctgggtca gacagaccac cagaccttac agccaagtga atgtgctgaa cttcaccacc 2400
agctggacag atggcctggc cttcaatgct gtgctgcaca gacacaagcc agacctgttc 2460
agctgggaca aagtggtcaa gatgagcccc attgagagac tggaacatgc cttcagcaag 2520
gcccagacct acctgggcat tgaaaaactg ctggatcctg aggatgtggc agtgcagctg 2580
cctgacaaga aatccatcat catgtacctg accagcctgt ttgaggtgct gcctcagcaa 2640
gtgaccattg atgccatcag agaggtggaa accctgccta gaaagtacaa gaaagagtgt 2700
gaagaggaag ccatcaacat ccagagcaca gcccctgaag aggaacatga gagccccaga 2760
gctgagacac ccagcacagt gacagaggtg gacatggacc tggacagcta ccagattgcc 2820
ctggaagagg tgctgacctg gctgctgtct gctgaggaca ccttccaaga gcaggatgac 2880
atctctgatg atgtggaaga agtgaaggac cagtttgcca cacatgaggc tttcatgatg 2940
gaactgacag cccaccagtc ctctgtgggc tctgttctgc aagctggaaa ccagctgatc 3000
acccagggca ccctgagtga tgaggaagag tttgagatcc aagaacagat gaccctgctg 3060
aatgccagat gggaagccct gagagtggaa tccatggaca gacagagcag actgcatgat 3120
gtgctcatgg aactgcagaa aaagcagctg cagcaactgt ctgcctggct gacactgaca 3180
gaagaaagga tccagaagat ggaaacctgt ccactggatg atgatgttaa gagcctgcag 3240
aagctcctgg aagaacacaa gtccctgcag tctgacctgg aagctgagca agtcaaagtg 3300
aacagcctga cacacatggt ggtcatagtg gatgagaact ctggggagtc tgccacagcc 3360
attctggaag atcagctcca gaaactggga gaaagatgga cagctgtgtg cagatggact 3420
gaggaaaggt ggaacagact gcaagagatc aatatcctgt ggcaagagct gcttgaggaa 3480
cagtgcctgc tgaaagcttg gctgactgag aaagaagagg ctctgaacaa ggtgcagacc 3540
agcaacttca aggaccagaa agaactgtct gtgtctgtca gaaggctggc catcctgaaa 3600
gaggacatgg aaatgaagag acagaccctg gaccagctgt ctgagattgg ccaggatgtg 3660
ggccagcttc tggacaactc taaggccagc aagaagatca actctgactc tgaggaactg 3720
acccagagat gggactccct ggtgcagagg ctggaagata gcagcaatca agtgacccag 3780
gctgtggcca agctgggcat gtctcagatc cctcagaagg atctgctgga aacagttaga 3840
gttagagagc aggccatcac caagaagtcc aagcaagaac tggaagccag ctctgaccag 3900
tggaagaggc tgcacctgag cctccaagaa ctgcttgtgt ggctgcagct caaggatgat 3960
gagctgagca gacaggcccc tattggtgga gacttccctg ctgtgcagaa acagaatgat 4020
gtccacaggg ccttcaagag ggaactcaag accaaagaac ctgtgatcat gagcaccctg 4080
gaaactgtca gaatcttcct gactgagcag cccctggaag gactggaaaa gctgtaccaa 4140
gagcctagag agctgcctcc tgaagaaagg gcccagaatg tgacaagact gctgagaaag 4200
caggctgagg aagtgaacac tgagtgggag aagctgaatc tgcactctgc tgactggcag 4260
agaaagatag atgagacact ggaaaggctc caagagttgc aagaggccac agatgagctg 4320
gatctgaaac tgagacaggc tgaagtgatc aaaggcagct ggcagcctgt gggagatctg 4380
ctgattgaca gcctgcagga ccacctggaa aaagtcaagg ccctgagggg agagattgcc 4440
cctctgaaag aaaatgtgtc ccatgtgaat gacctggcca gacagctcac cacactgggc 4500
attcaactga gcccctacaa cctgtctacc cttgaggacc tgaacaccag atggaagctg 4560
ctccaggtgg cagttgagga cagagttaga cagctgcatg aggctcacag agactttggc 4620
cctgccagcc agcacttcct gagcacctct gtgcaaggcc cttgggagag agctatcagc 4680
cccaacaaag tgccctacta catcaaccat gagactcaga ccacctgttg ggatcacccc 4740
aagatgacag agctgtatca gagcctggca gacctcaaca atgtcagatt cagtgcctac 4800
aggacagcca tgaagctgag aaggctccag aaggccctct gcctggatct cctgtctctg 4860
tctgcagctt gtgatgccct ggatcagcac aacctgaagc agaatgatca gcccatggac 4920
atcctgcaga tcatcaactg cctgaccaca atctatgaca ggctggaaca agagcacaac 4980
aacctggtca atgtgcccct gtgtgtggac atgtgcctga attggctgct caatgtgtat 5040
gacacaggca ggacaggcag aatcagggtg ctgagcttca agacaggcat catcagcctg 5100
tgcaaagctc acttggagga caagtacaga tacctgttca aacaggtggc cagcagcaca 5160
ggcttttgtg accagagaag gcttggcctg ctgctgcatg acagcattca gatccccagg 5220
cagcttggag aggtggcctc ctttggaggc agcaatattg agccctctgt caggtcctgt 5280
ttccaatttg ccaacaacaa gcctgagatt gaggctgccc tgttcctgga ctggatgaga 5340
cttgagcccc agtccatggt ctggctgcca gtgctgcata gagtggctgc tgcagagaca 5400
gccaagcacc aggccaaatg caacatctgc aaagagtgcc ccatcattgg cttcagatac 5460
agaagcctga agcacttcaa ctatgatatc tgccagagct gtttctttag tggcagagtg 5520
gccaagggcc acaagatgca ctaccccatg gtggaatact gcacccctac cacctctggg 5580
gaagatgtta gagattttgc caaggtgctg aagaacaagt tcaggaccaa gagatacttt 5640
gctaagcacc ccaggatggg ctatctgcct gtgcagacag tgcttgaggg agacaacatg 5700
gaaacatgat gaggagctcg agaggcctaa taaagagctc agatgcatcg atcagagtgt 5760
gttggttttt tgtgtgagat ctaggaaccc ctagtgatgg agttggccac tccctctctg 5820
cgcgctcgct cgctcactga ggccgcccgg gcaaagcccg ggcgtcgggc gacctttggt 5880
cgcccggcct cagtgagcga gcgagcgcgc agagagggag tggccaaccc cccccccccc 5940
ccccctgcag gcgattctct tgtttgctcc agactctcag gcaatgacct gatagccttt 6000
gtagagacct ctcaaaaata gctaccctct ccggcatgaa tttatcagct agaacggttg 6060
aatatcatat tgatggtgat ttgactgtct ccggcctttc tcacccgttt gaatctttac 6120
ctacacatta ctcaggcatt gcatttaaaa tatatgaggg ttctaaaaat ttttatcctt 6180
gcgttgaaat aaaggcttct cccgcaaaag tattacaggg tcataatgtt tttggtacaa 6240
ccgatttagc tttatgctct gaggctttat tgcttaattt tgctaattct ttgccttgcc 6300
tgtatgattt attggatgtt ggaatcgcct gatgcggtat tttctcctta cgcatctgtg 6360
cggtatttca caccgcatat ggtgcactct cagtacaatc tgctctgatg ccgcatagtt 6420
aagccagccc cgacacccgc caacacccgc tgacgcgccc tgacgggctt gtctgctccc 6480
ggcatccgct tacagacaag ctgtgaccgt ctccgggagc tgcatgtgtc agaggttttc 6540
accgtcatca ccgaaacgcg cgagacgaaa gggcctcgtg atacgcctat ttttataggt 6600
taatgtcatg ataataatgg tttcttagac gtcaggtggc acttttcggg gaaatgtgcg 6660
cggaacccct atttgtttat ttttctaaat acattcaaat atgtatccgc tcatgagaca 6720
ataaccctga taaatgcttc aataatattg aaaaaggaag agtatgattg aacaagatgg 6780
attgcacgca ggttctccgg ccgcttgggt ggagaggcta ttcggctatg actgggcaca 6840
acagacaatc ggctgctctg atgccgccgt gttccggctg tcagcgcagg ggcgcccggt 6900
tctttttgtc aagaccgacc tgtccggtgc cctgaatgaa ctgcaagacg aggcagcgcg 6960
gctatcgtgg ctggccacga cgggcgttcc ttgcgcagct gtgctcgatg ttgtcactga 7020
agcgggaagg gactggctgc tattgggcga agtgccgggg caggatctcc tgtcatctca 7080
ccttgctcct gccgagaaag tatccatcat ggctgatgca atgcggcggc tgcatacgct 7140
tgatccggct acctgcccat tcgaccacca agcgaaacat cgcatcgagc gagcacgtac 7200
tcggatggaa gccggtcttg tcgatcagga tgatctggac gaagagcatc aggggctcgc 7260
gccagccgaa ctgttcgcca ggctcaaggc gagcatgccc gacggcgagg atctcgtcgt 7320
gacccatggc gatgcctgct tgccgaatat catggtggaa aatggccgct tttctggatt 7380
catcgactgt ggccggctgg gtgtggcgga ccgctatcag gacatagcgt tggctacccg 7440
tgatattgct gaagagcttg gcggcgaatg ggctgaccgc ttcctcgtgc tttacggtat 7500
cgccgctccc gattcgcagc gcatcgcctt ctatcgcctt cttgacgagt tcttctgact 7560
gtcagaccaa gtttactcat atatacttta gattgattta aaacttcatt tttaatttaa 7620
aaggatctag gtgaagatcc tttttgataa tctcatgacc aaaatccctt aacgtgagtt 7680
ttcgttccac tgagcgtcag accccgtaga aaagatcaaa ggatcttctt gagatccttt 7740
ttttctgcgc gtaatctgct gcttgcaaac aaaaaaacca ccgctaccag cggtggtttg 7800
tttgccggat caagagctac caactctttt tccgaaggta actggcttca gcagagcgca 7860
gataccaaat actgttcttc tagtgtagcc gtagttaggc caccacttca agaactctgt 7920
agcaccgcct acatacctcg ctctgctaat cctgttacca gtggctgctg ccagtggcga 7980
taagtcgtgt cttaccgggt tggactcaag acgatagtta ccggataagg cgcagcggtc 8040
gggctgaacg gggggttcgt gcacacagcc cagcttggag cgaacgacct acaccgaact 8100
gagataccta cagcgtgagc tatgagaaag cgccacgctt cccgaaggga gaaaggcgga 8160
caggtatccg gtaagcggca gggtcggaac aggagagcgc acgagggagc ttccaggggg 8220
aaacgcctgg tatctttata gtcctgtcgg gtttcgccac ctctgacttg agcgtcgatt 8280
tttgtgatgc tcgtcagggg ggcggagcct atggaaaaac gccagcaacg cggccttttt 8340
acggttcctg gccttttgct ggccttttgc tcacatgttc tttcctgcgt tatcccctga 8400
ttctgtggat aaccgtatta ccgcctttga gtgagctgat accgctcgcc gcagccgaac 8460
gaccgagcgc agcgagtcag tgagcgagga agcggaagag cgcccaatac gcaaaccgcc 8520
tctccccgcg cgttggccga ttcattaatg cagaattccc atcatcaata atatacctta 8580
ttttggattg aagccaatat gataatgagg gggtggagtt tgtgacgtgg cgcggggcgt 8640
gggaacgggg cgggtgacgt agtagct 8667
<210> 4
<211> 1279
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 重组融合蛋白(即M6和opti-M6构建体蛋白产物)的氨基酸序列
<400> 4
Met Ala Lys Tyr Gly Glu His Glu Ala Ser Pro Asp Asn Gly Gln Asn
1 5 10 15
Glu Phe Ser Asp Ile Ile Lys Ser Arg Ser Asp Glu His Asn Asp Val
20 25 30
Gln Lys Lys Thr Phe Thr Lys Trp Ile Asn Ala Arg Phe Ser Lys Ser
35 40 45
Gly Lys Pro Pro Ile Asn Asp Met Phe Thr Asp Leu Lys Asp Gly Arg
50 55 60
Lys Leu Leu Asp Leu Leu Glu Gly Leu Thr Gly Thr Ser Leu Pro Lys
65 70 75 80
Glu Arg Gly Ser Thr Arg Val His Ala Leu Asn Asn Val Asn Arg Val
85 90 95
Leu Gln Val Leu His Gln Asn Asn Val Glu Leu Val Asn Ile Gly Gly
100 105 110
Thr Asp Ile Val Asp Gly Asn His Lys Leu Thr Leu Gly Leu Leu Trp
115 120 125
Ser Ile Ile Leu His Trp Gln Val Lys Asp Val Met Lys Asp Val Met
130 135 140
Ser Asp Leu Gln Gln Thr Asn Ser Glu Lys Ile Leu Leu Ser Trp Val
145 150 155 160
Arg Gln Thr Thr Arg Pro Tyr Ser Gln Val Asn Val Leu Asn Phe Thr
165 170 175
Thr Ser Trp Thr Asp Gly Leu Ala Phe Asn Ala Val Leu His Arg His
180 185 190
Lys Pro Asp Leu Phe Ser Trp Asp Lys Val Val Lys Met Ser Pro Ile
195 200 205
Glu Arg Leu Glu His Ala Phe Ser Lys Ala Gln Thr Tyr Leu Gly Ile
210 215 220
Glu Lys Leu Leu Asp Pro Glu Asp Val Ala Val Gln Leu Pro Asp Lys
225 230 235 240
Lys Ser Ile Ile Met Tyr Leu Thr Ser Leu Phe Glu Val Leu Pro Gln
245 250 255
Gln Val Thr Ile Asp Ala Ile Arg Glu Val Glu Thr Leu Pro Arg Lys
260 265 270
Tyr Lys Lys Glu Cys Glu Glu Glu Ala Ile Asn Ile Gln Ser Thr Ala
275 280 285
Pro Glu Glu Glu His Glu Ser Pro Arg Ala Glu Thr Pro Ser Thr Val
290 295 300
Thr Glu Val Asp Met Asp Leu Asp Ser Tyr Gln Ile Ala Leu Glu Glu
305 310 315 320
Val Leu Thr Trp Leu Leu Ser Ala Glu Asp Thr Phe Gln Glu Gln Asp
325 330 335
Asp Ile Ser Asp Asp Val Glu Glu Val Lys Asp Gln Phe Ala Thr His
340 345 350
Glu Ala Phe Met Met Glu Leu Thr Ala His Gln Ser Ser Val Gly Ser
355 360 365
Val Leu Gln Ala Gly Asn Gln Leu Ile Thr Gln Gly Thr Leu Ser Asp
370 375 380
Glu Glu Glu Phe Glu Ile Gln Glu Gln Met Thr Leu Leu Asn Ala Arg
385 390 395 400
Trp Glu Ala Leu Arg Val Glu Ser Met Asp Arg Gln Ser Arg Leu His
405 410 415
Asp Val Leu Met Glu Leu Gln Lys Lys Gln Leu Gln Gln Leu Ser Ala
420 425 430
Trp Leu Thr Leu Thr Glu Glu Arg Ile Gln Lys Met Glu Thr Cys Pro
435 440 445
Leu Asp Asp Asp Val Lys Ser Leu Gln Lys Leu Leu Glu Glu His Lys
450 455 460
Ser Leu Gln Ser Asp Leu Glu Ala Glu Gln Val Lys Val Asn Ser Leu
465 470 475 480
Thr His Met Val Val Ile Val Asp Glu Asn Ser Gly Glu Ser Ala Thr
485 490 495
Ala Ile Leu Glu Asp Gln Leu Gln Lys Leu Gly Glu Arg Trp Thr Ala
500 505 510
Val Cys Arg Trp Thr Glu Glu Arg Trp Asn Arg Leu Gln Glu Ile Asn
515 520 525
Ile Leu Trp Gln Glu Leu Leu Glu Glu Gln Cys Leu Leu Lys Ala Trp
530 535 540
Leu Thr Glu Lys Glu Glu Ala Leu Asn Lys Val Gln Thr Ser Asn Phe
545 550 555 560
Lys Asp Gln Lys Glu Leu Ser Val Ser Val Arg Arg Leu Ala Ile Leu
565 570 575
Lys Glu Asp Met Glu Met Lys Arg Gln Thr Leu Asp Gln Leu Ser Glu
580 585 590
Ile Gly Gln Asp Val Gly Gln Leu Leu Asp Asn Ser Lys Ala Ser Lys
595 600 605
Lys Ile Asn Ser Asp Ser Glu Glu Leu Thr Gln Arg Trp Asp Ser Leu
610 615 620
Val Gln Arg Leu Glu Asp Ser Ser Asn Gln Val Thr Gln Ala Val Ala
625 630 635 640
Lys Leu Gly Met Ser Gln Ile Pro Gln Lys Asp Leu Leu Glu Thr Val
645 650 655
Arg Val Arg Glu Gln Ala Ile Thr Lys Lys Ser Lys Gln Glu Leu Glu
660 665 670
Ala Ser Ser Asp Gln Trp Lys Arg Leu His Leu Ser Leu Gln Glu Leu
675 680 685
Leu Val Trp Leu Gln Leu Lys Asp Asp Glu Leu Ser Arg Gln Ala Pro
690 695 700
Ile Gly Gly Asp Phe Pro Ala Val Gln Lys Gln Asn Asp Val His Arg
705 710 715 720
Ala Phe Lys Arg Glu Leu Lys Thr Lys Glu Pro Val Ile Met Ser Thr
725 730 735
Leu Glu Thr Val Arg Ile Phe Leu Thr Glu Gln Pro Leu Glu Gly Leu
740 745 750
Glu Lys Leu Tyr Gln Glu Pro Arg Glu Leu Pro Pro Glu Glu Arg Ala
755 760 765
Gln Asn Val Thr Arg Leu Leu Arg Lys Gln Ala Glu Glu Val Asn Thr
770 775 780
Glu Trp Glu Lys Leu Asn Leu His Ser Ala Asp Trp Gln Arg Lys Ile
785 790 795 800
Asp Glu Thr Leu Glu Arg Leu Gln Glu Leu Gln Glu Ala Thr Asp Glu
805 810 815
Leu Asp Leu Lys Leu Arg Gln Ala Glu Val Ile Lys Gly Ser Trp Gln
820 825 830
Pro Val Gly Asp Leu Leu Ile Asp Ser Leu Gln Asp His Leu Glu Lys
835 840 845
Val Lys Ala Leu Arg Gly Glu Ile Ala Pro Leu Lys Glu Asn Val Ser
850 855 860
His Val Asn Asp Leu Ala Arg Gln Leu Thr Thr Leu Gly Ile Gln Leu
865 870 875 880
Ser Pro Tyr Asn Leu Ser Thr Leu Glu Asp Leu Asn Thr Arg Trp Lys
885 890 895
Leu Leu Gln Val Ala Val Glu Asp Arg Val Arg Gln Leu His Glu Ala
900 905 910
His Arg Asp Phe Gly Pro Ala Ser Gln His Phe Leu Ser Thr Ser Val
915 920 925
Gln Gly Pro Trp Glu Arg Ala Ile Ser Pro Asn Lys Val Pro Tyr Tyr
930 935 940
Ile Asn His Glu Thr Gln Thr Thr Cys Trp Asp His Pro Lys Met Thr
945 950 955 960
Glu Leu Tyr Gln Ser Leu Ala Asp Leu Asn Asn Val Arg Phe Ser Ala
965 970 975
Tyr Arg Thr Ala Met Lys Leu Arg Arg Leu Gln Lys Ala Leu Cys Leu
980 985 990
Asp Leu Leu Ser Leu Ser Ala Ala Cys Asp Ala Leu Asp Gln His Asn
995 1000 1005
Leu Lys Gln Asn Asp Gln Pro Met Asp Ile Leu Gln Ile Ile Asn
1010 1015 1020
Cys Leu Thr Thr Ile Tyr Asp Arg Leu Glu Gln Glu His Asn Asn
1025 1030 1035
Leu Val Asn Val Pro Leu Cys Val Asp Met Cys Leu Asn Trp Leu
1040 1045 1050
Leu Asn Val Tyr Asp Thr Gly Arg Thr Gly Arg Ile Arg Val Leu
1055 1060 1065
Ser Phe Lys Thr Gly Ile Ile Ser Leu Cys Lys Ala His Leu Glu
1070 1075 1080
Asp Lys Tyr Arg Tyr Leu Phe Lys Gln Val Ala Ser Ser Thr Gly
1085 1090 1095
Phe Cys Asp Gln Arg Arg Leu Gly Leu Leu Leu His Asp Ser Ile
1100 1105 1110
Gln Ile Pro Arg Gln Leu Gly Glu Val Ala Ser Phe Gly Gly Ser
1115 1120 1125
Asn Ile Glu Pro Ser Val Arg Ser Cys Phe Gln Phe Ala Asn Asn
1130 1135 1140
Lys Pro Glu Ile Glu Ala Ala Leu Phe Leu Asp Trp Met Arg Leu
1145 1150 1155
Glu Pro Gln Ser Met Val Trp Leu Pro Val Leu His Arg Val Ala
1160 1165 1170
Ala Ala Glu Thr Ala Lys His Gln Ala Lys Cys Asn Ile Cys Lys
1175 1180 1185
Glu Cys Pro Ile Ile Gly Phe Arg Tyr Arg Ser Leu Lys His Phe
1190 1195 1200
Asn Tyr Asp Ile Cys Gln Ser Cys Phe Phe Ser Gly Arg Val Ala
1205 1210 1215
Lys Gly His Lys Met His Tyr Pro Met Val Glu Tyr Cys Thr Pro
1220 1225 1230
Thr Thr Ser Gly Glu Asp Val Arg Asp Phe Ala Lys Val Leu Lys
1235 1240 1245
Asn Lys Phe Arg Thr Lys Arg Tyr Phe Ala Lys His Pro Arg Met
1250 1255 1260
Gly Tyr Leu Pro Val Gln Thr Val Leu Glu Gly Asp Asn Met Glu
1265 1270 1275
Thr
<210> 5
<211> 8667
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> hCK-M6表达盒的核苷酸序列
<400> 5
ctagaggtcc ccagcgacct tgacgagcat ctgcccggca tttctgacag ctttgtgaac 60
tgggtggccg agaaggaatg ggagttgccg ccagattctg acatggatct gaatctgatt 120
gagcaggcac ccctgaccgt ggccgagaag ctgcatcgct ggcgtaatag cgaagaggcc 180
cgcaccgatc gcccttccca acagttgcgc agcctgaatg gcgaatggcg attccgttgc 240
aatggctggc ggtaatattg ttctggatat taccagcaag gccgatagtt tgagttcttc 300
tactcaggca agtgatgtta ttactaatca aagaagtatt gcgacaacgg ttaatttgcg 360
tgatggacag actcttttac tcggtggcct cactgattat aaaaacactt ctcaggattc 420
tggcgtaccg ttcctgtcta aaatcccttt aatcggcctc ctgtttagct cccgctctga 480
ttctaacgag gaaagcacgt tatacgtgct cgtcaaagca accatagtac gcgccctgta 540
gcggcgcatt aagcgcggcg ggtgtggtgg ttacgcgcag cgtgaccgct acacttgcca 600
gcgccctagc gcccgctcct ttcgctttct tcccttcctt tctcgccacg ttcgccggct 660
ttccccgtca agctctaaat cgggggctcc ctttagggtt ccgatttagt gctttacggc 720
acctcgaccc caaaaaactt gattagggtg atggttcacg tagtgggcca tcgccctgat 780
agacggtttt tcgccctttg acgttggagt ccacgttctt aatagtggac tcttgttcca 840
aactggaaca acactcaacc ctatctcggt ctattctttt gatttataag ggattttgcc 900
gatttcggcc tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattttaa 960
caaaatatta acgcttacaa tttaaatatt tgcttataca atcttcctgt ttttggggct 1020
tttctgatta tcaaccgggg tacatatgat tgacatgcta gttttacgat taccgttcat 1080
cgcctgcagg gggggggggg ggggggttgg ccactccctc tctgcgcgct cgctcgctca 1140
ctgaggccgg gcgaccaaag gtcgcccgac gcccgggctt tgcccgggcg gcctcagtga 1200
gcgagcgagc gcgcagagag ggagtggcca actccatcac taggggttcc tagatctgaa 1260
ttcggtaccc cactacgggt ttaggctgcc catgtaagga ggcaaggcct ggggacaccc 1320
gagatgcctg gttataatta acccagacat gtggctgccc cccccccccc caacacctgc 1380
tgcctctaaa aataaccctg tccctggtgg atcccctgca tgcgaagatc ttcgaacaag 1440
gctgtggggg actgagggca ggctgtaaca ggcttggggg ccagggctta tacgtgcctg 1500
ggactcccaa agtattactg ttccatgttc ccggcgaagg gccagctgtc ccccgccagc 1560
tagactcagc acttagttta ggaaccagtg agcaagtcag cccttggggc agcccataca 1620
aggccatggg gctgggcaag ctgcacgcct gggtccgggg tgggcacggt gcccgggcaa 1680
cgagctgaaa gctcatctgc tctcaggggc ccctccctgg ggacagcccc tcctggctag 1740
tcacaccctg taggctcctc tatataaccc aggggcacag gggctgccct cattctacca 1800
ccacctccac agcacagaca gacactcagg agccagccag cgtcgagcgg ccgatccgcc 1860
accgccacca tggccaaata tggcgagcat gaggctagcc ccgacaacgg ccagaacgag 1920
ttcagcgaca tcatcaagag cagaagcgac gagcacaacg acgtgcagaa gaaaaccttc 1980
accaagtgga tcaacgcccg gttcagcaag agcggcaagc ctcctatcaa cgacatgttc 2040
accgacctga aggacggcag aaagctgctg gatctgctgg aaggcctgac cggcacaagc 2100
ctgcctaaag aaaggggcag cacaagagtg cacgccctga acaacgtgaa ccgggtgctg 2160
caggttctgc accagaacaa tgtggaactg gtcaacatcg gcggcaccga catcgtggac 2220
ggcaatcaca aactgaccct gggcctgctg tggtccatca tcctgcactg gcaagtgaaa 2280
gacgtgatga aggatgtgat gagcgatctg cagcagacca acagcgagaa gatcctgctg 2340
agctgggtcc gacagaccac cagaccttac agccaagtga acgtgctgaa cttcaccacc 2400
agctggacag acggcctggc ctttaatgcc gtgctgcaca gacacaagcc cgacctgttc 2460
agctgggaca aagtggtcaa gatgagcccc atcgagcggc tggaacacgc cttttctaag 2520
gcccagacct acctgggcat cgaaaaactg ctggaccccg aggatgtggc cgtgcagctg 2580
cctgacaaga aatccatcat catgtacctg accagcctgt tcgaggtgct gcctcagcaa 2640
gtgaccatcg acgccatcag agaggtggaa accctgcctc ggaagtacaa gaaagagtgc 2700
gaggaagagg ccatcaacat ccagagcaca gcccctgagg aagaacacga gagccctaga 2760
gccgagacac ctagcacagt gaccgaggtg gacatggacc tggacagcta tcagatcgcc 2820
ctggaagagg tgctgacctg gctgctgtct gccgaggata ccttccaaga gcaggacgac 2880
atcagcgacg acgtggaaga agtgaaggac cagttcgcca cacacgaggc cttcatgatg 2940
gaactgacag cccaccagtc tagcgtgggc tctgttctgc aagccggcaa ccagctgatc 3000
acccagggca ccctgtctga tgaggaagag ttcgagatcc aagaacagat gaccctgctg 3060
aacgccagat gggaagccct gagagtggaa tccatggacc ggcagagcag actgcacgac 3120
gtgctcatgg aactgcagaa aaagcagctg cagcagctca gcgcctggct gacactgacc 3180
gaagaacgga tccagaagat ggaaacctgt cctctggacg acgatgtgaa gtccctgcag 3240
aagctgctcg aggaacacaa gagcctgcag agcgacctgg aagccgagca agtcaaagtg 3300
aacagcctga cacacatggt cgtgatcgtg gatgagaaca gcggcgagtc tgccacagcc 3360
atcctggaag atcagctgca gaaactgggc gagagatgga ccgccgtgtg cagatggaca 3420
gaggaacggt ggaaccggct gcaagagatc aatatcctgt ggcaagaact cctcgaagaa 3480
cagtgtctgc tgaaggcttg gctgaccgag aaagaagagg ctctgaacaa ggtgcagacc 3540
agcaacttca aggaccagaa agaactgagc gtgtccgtgc ggagactggc cattctgaaa 3600
gaggacatgg aaatgaagcg gcagaccctg gaccagctgt ctgagatcgg acaggatgtg 3660
ggccagctcc tggacaatag caaggccagc aagaagatca acagcgacag cgaggaactg 3720
acccagagat gggattcact ggtgcagcgg ctcgaggaca gcagcaatca agtgacacag 3780
gccgtggcca agctgggcat gtctcagatc cctcagaagg acctgctgga aaccgtcaga 3840
gtcagagagc aggccatcac caagaagtcc aagcaagaac tggaagccag ctccgaccag 3900
tggaagagac tgcacctgtc tctgcaagag ctgctcgtgt ggctgcagct caaggacgat 3960
gagctgagca gacaggcccc tatcggcgga gattttcccg ccgtgcagaa acagaacgat 4020
gtgcaccggg ccttcaagcg cgagctgaaa acaaaagaac ccgtgatcat gagcaccctg 4080
gaaacagtgc ggatcttcct gaccgagcag cccctggaag gactggaaaa gctgtaccaa 4140
gagcctagag agctgcctcc tgaagaacgg gcccagaacg tgaccagact gctgagaaag 4200
caggccgagg aagtgaacac cgagtgggag aagctgaacc tgcacagcgc cgactggcag 4260
cggaagattg acgagacact ggaaagactc caagaactgc aagaggccac cgacgagctg 4320
gacctgaaac tgagacaggc cgaagtgatc aaaggcagct ggcagcctgt gggcgacctg 4380
ctgattgata gcctgcagga ccacctcgag aaagtgaagg ctctgagagg cgagatcgcc 4440
cctctgaaag aaaacgtgtc ccacgtgaac gacctggctc ggcagctgac aacactggga 4500
attcagctga gcccctacaa cctgtccaca ctcgaggacc tgaacacccg gtggaaactg 4560
cttcaggtgg ccgtggaaga tagagtgcgc cagctgcatg aggcccacag agattttgga 4620
cctgccagcc agcacttcct gagcacctct gtgcaaggcc cttgggagag agctatcagc 4680
cccaacaaag tgccctacta catcaaccac gagacacaga ccacatgctg ggatcacccc 4740
aagatgaccg agctgtatca gagcctggcc gacctcaaca acgtgcggtt tagcgcctac 4800
cggaccgcca tgaagctgcg gaggctgcaa aaagccctgt gcctggatct cctgagcctg 4860
agcgctgctt gtgatgccct ggatcagcac aatctgaagc agaacgacca gcctatggac 4920
atcctgcaga tcatcaactg cctgaccacc atctacgacc gcctggaaca agagcacaac 4980
aacctggtca acgtgcccct gtgcgtggac atgtgcctga attggctgct gaatgtgtac 5040
gacaccggca gaaccggcag gatcagagtg ctgagcttca agaccggcat catcagcctg 5100
tgcaaagccc accttgagga caagtaccgc tacctgttca aacaggtggc cagcagcacc 5160
ggcttttgcg accaaagaag gctgggactg ctgctgcacg acagcattca gatcccacgg 5220
cagctgggag aagtggccag ctttggcggc agcaatatcg agcctagcgt gcggtcctgc 5280
tttcagtttg ccaacaacaa gcctgagatc gaggccgctc tgttcctgga ctggatgaga 5340
ctggaacccc agagcatggt ctggctgcct gtgctgcata gagtggctgc cgccgaaaca 5400
gccaagcacc aggccaagtg caacatctgc aaagagtgcc ccatcatcgg cttccggtac 5460
agaagcctga agcacttcaa ctacgatatc tgccagtcct gcttcttcag cggcagagtg 5520
gccaagggcc acaagatgca ctaccccatg gtggaatact gcacccctac caccagcgga 5580
gaggacgtgc gggattttgc caaggtgctg aagaacaagt tccggaccaa gcgctacttc 5640
gctaagcacc ccagaatggg ctatctgccc gtgcagacag tcctggaagg cgacaacatg 5700
gaaacctgat gaggagctcg agaggcctaa taaagagctc agatgcatcg atcagagtgt 5760
gttggttttt tgtgtgagat ctaggaaccc ctagtgatgg agttggccac tccctctctg 5820
cgcgctcgct cgctcactga ggccgcccgg gcaaagcccg ggcgtcgggc gacctttggt 5880
cgcccggcct cagtgagcga gcgagcgcgc agagagggag tggccaaccc cccccccccc 5940
ccccctgcag gcgattctct tgtttgctcc agactctcag gcaatgacct gatagccttt 6000
gtagagacct ctcaaaaata gctaccctct ccggcatgaa tttatcagct agaacggttg 6060
aatatcatat tgatggtgat ttgactgtct ccggcctttc tcacccgttt gaatctttac 6120
ctacacatta ctcaggcatt gcatttaaaa tatatgaggg ttctaaaaat ttttatcctt 6180
gcgttgaaat aaaggcttct cccgcaaaag tattacaggg tcataatgtt tttggtacaa 6240
ccgatttagc tttatgctct gaggctttat tgcttaattt tgctaattct ttgccttgcc 6300
tgtatgattt attggatgtt ggaatcgcct gatgcggtat tttctcctta cgcatctgtg 6360
cggtatttca caccgcatat ggtgcactct cagtacaatc tgctctgatg ccgcatagtt 6420
aagccagccc cgacacccgc caacacccgc tgacgcgccc tgacgggctt gtctgctccc 6480
ggcatccgct tacagacaag ctgtgaccgt ctccgggagc tgcatgtgtc agaggttttc 6540
accgtcatca ccgaaacgcg cgagacgaaa gggcctcgtg atacgcctat ttttataggt 6600
taatgtcatg ataataatgg tttcttagac gtcaggtggc acttttcggg gaaatgtgcg 6660
cggaacccct atttgtttat ttttctaaat acattcaaat atgtatccgc tcatgagaca 6720
ataaccctga taaatgcttc aataatattg aaaaaggaag agtatgattg aacaagatgg 6780
attgcacgca ggttctccgg ccgcttgggt ggagaggcta ttcggctatg actgggcaca 6840
acagacaatc ggctgctctg atgccgccgt gttccggctg tcagcgcagg ggcgcccggt 6900
tctttttgtc aagaccgacc tgtccggtgc cctgaatgaa ctgcaagacg aggcagcgcg 6960
gctatcgtgg ctggccacga cgggcgttcc ttgcgcagct gtgctcgatg ttgtcactga 7020
agcgggaagg gactggctgc tattgggcga agtgccgggg caggatctcc tgtcatctca 7080
ccttgctcct gccgagaaag tatccatcat ggctgatgca atgcggcggc tgcatacgct 7140
tgatccggct acctgcccat tcgaccacca agcgaaacat cgcatcgagc gagcacgtac 7200
tcggatggaa gccggtcttg tcgatcagga tgatctggac gaagagcatc aggggctcgc 7260
gccagccgaa ctgttcgcca ggctcaaggc gagcatgccc gacggcgagg atctcgtcgt 7320
gacccatggc gatgcctgct tgccgaatat catggtggaa aatggccgct tttctggatt 7380
catcgactgt ggccggctgg gtgtggcgga ccgctatcag gacatagcgt tggctacccg 7440
tgatattgct gaagagcttg gcggcgaatg ggctgaccgc ttcctcgtgc tttacggtat 7500
cgccgctccc gattcgcagc gcatcgcctt ctatcgcctt cttgacgagt tcttctgact 7560
gtcagaccaa gtttactcat atatacttta gattgattta aaacttcatt tttaatttaa 7620
aaggatctag gtgaagatcc tttttgataa tctcatgacc aaaatccctt aacgtgagtt 7680
ttcgttccac tgagcgtcag accccgtaga aaagatcaaa ggatcttctt gagatccttt 7740
ttttctgcgc gtaatctgct gcttgcaaac aaaaaaacca ccgctaccag cggtggtttg 7800
tttgccggat caagagctac caactctttt tccgaaggta actggcttca gcagagcgca 7860
gataccaaat actgttcttc tagtgtagcc gtagttaggc caccacttca agaactctgt 7920
agcaccgcct acatacctcg ctctgctaat cctgttacca gtggctgctg ccagtggcga 7980
taagtcgtgt cttaccgggt tggactcaag acgatagtta ccggataagg cgcagcggtc 8040
gggctgaacg gggggttcgt gcacacagcc cagcttggag cgaacgacct acaccgaact 8100
gagataccta cagcgtgagc tatgagaaag cgccacgctt cccgaaggga gaaaggcgga 8160
caggtatccg gtaagcggca gggtcggaac aggagagcgc acgagggagc ttccaggggg 8220
aaacgcctgg tatctttata gtcctgtcgg gtttcgccac ctctgacttg agcgtcgatt 8280
tttgtgatgc tcgtcagggg ggcggagcct atggaaaaac gccagcaacg cggccttttt 8340
acggttcctg gccttttgct ggccttttgc tcacatgttc tttcctgcgt tatcccctga 8400
ttctgtggat aaccgtatta ccgcctttga gtgagctgat accgctcgcc gcagccgaac 8460
gaccgagcgc agcgagtcag tgagcgagga agcggaagag cgcccaatac gcaaaccgcc 8520
tctccccgcg cgttggccga ttcattaatg cagaattccc atcatcaata atatacctta 8580
ttttggattg aagccaatat gataatgagg gggtggagtt tgtgacgtgg cgcggggcgt 8640
gggaacgggg cgggtgacgt agtagct 8667
<210> 6
<211> 8641
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> shCK-opti-M6表达盒的核苷酸序列
<400> 6
ctagaggtcc ccagcgacct tgacgagcat ctgcccggca tttctgacag ctttgtgaac 60
tgggtggccg agaaggaatg ggagttgccg ccagattctg acatggatct gaatctgatt 120
gagcaggcac ccctgaccgt ggccgagaag ctgcatcgct ggcgtaatag cgaagaggcc 180
cgcaccgatc gcccttccca acagttgcgc agcctgaatg gcgaatggcg attccgttgc 240
aatggctggc ggtaatattg ttctggatat taccagcaag gccgatagtt tgagttcttc 300
tactcaggca agtgatgtta ttactaatca aagaagtatt gcgacaacgg ttaatttgcg 360
tgatggacag actcttttac tcggtggcct cactgattat aaaaacactt ctcaggattc 420
tggcgtaccg ttcctgtcta aaatcccttt aatcggcctc ctgtttagct cccgctctga 480
ttctaacgag gaaagcacgt tatacgtgct cgtcaaagca accatagtac gcgccctgta 540
gcggcgcatt aagcgcggcg ggtgtggtgg ttacgcgcag cgtgaccgct acacttgcca 600
gcgccctagc gcccgctcct ttcgctttct tcccttcctt tctcgccacg ttcgccggct 660
ttccccgtca agctctaaat cgggggctcc ctttagggtt ccgatttagt gctttacggc 720
acctcgaccc caaaaaactt gattagggtg atggttcacg tagtgggcca tcgccctgat 780
agacggtttt tcgccctttg acgttggagt ccacgttctt aatagtggac tcttgttcca 840
aactggaaca acactcaacc ctatctcggt ctattctttt gatttataag ggattttgcc 900
gatttcggcc tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattttaa 960
caaaatatta acgcttacaa tttaaatatt tgcttataca atcttcctgt ttttggggct 1020
tttctgatta tcaaccgggg tacatatgat tgacatgcta gttttacgat taccgttcat 1080
cgcctgcagg gggggggggg ggggggttgg ccactccctc tctgcgcgct cgctcgctca 1140
ctgaggccgg gcgaccaaag gtcgcccgac gcccgggctt tgcccgggcg gcctcagtga 1200
gcgagcgagc gcgcagagag ggagtggcca actccatcac taggggttcc tagatctgaa 1260
ttcggtaccc cactacgggt ttaggctgcc catgtaagga ggcaaggcct ggggacaccc 1320
gagatgcctg gttataatta acccagacat gtggctgccc cccccccccc caacacctgc 1380
tgcctctaaa aataaccctg tccctggtgg atcccctgca tgcgaagatc ttcgaacaag 1440
gctgtggggg actgagggca ggctgtaaca ggcttggggg ccagggctta tacgtgcctg 1500
ggactcccaa agtattactg ttccatgttc ccggcgaagg gccagctgtc ccccgccagc 1560
tagactcagc acttagttta ggaaccagtg agcaagtcag cccttggggc agcccataca 1620
aggccatggg gctgggcaag ctgcacgcct gggtccgggg tgggcacggt gcccgggcaa 1680
cgagctgaaa gctcatctgc tctcaggggc ccctccctgg ggacagcccc tcctggctag 1740
tcacaccctg taggctcctc tatataaccc aggggcacag gggctgccct cattctacca 1800
ccaccacagc acagacagac aaaactccta aaaaaccgcc accatggcca aatatgggga 1860
gcatgaggcc tctccagaca atggccagaa tgagttctct gacatcatca agagcagatc 1920
tgatgagcac aatgatgtgc agaagaaaac cttcaccaag tggatcaatg ccaggttcag 1980
caagtctggc aagcctccta tcaatgacat gttcacagac ctgaaggatg gcagaaagct 2040
gctggacctg ctggaaggcc tgacaggcac aagcctgcct aaagaaaggg gcagcaccag 2100
agtgcatgcc ctgaacaatg tgaacagagt gctgcaggtc ctgcaccaga acaatgttga 2160
gctggtcaat attggaggca cagacattgt ggatggcaac cacaagctga ccctgggcct 2220
gctgtggtcc atcatcctgc actggcaagt gaaagatgtg atgaaggatg tcatgtctga 2280
cctccagcag accaactctg agaagatcct gctgagctgg gtcagacaga ccaccagacc 2340
ttacagccaa gtgaatgtgc tgaacttcac caccagctgg acagatggcc tggccttcaa 2400
tgctgtgctg cacagacaca agccagacct gttcagctgg gacaaagtgg tcaagatgag 2460
ccccattgag agactggaac atgccttcag caaggcccag acctacctgg gcattgaaaa 2520
actgctggat cctgaggatg tggcagtgca gctgcctgac aagaaatcca tcatcatgta 2580
cctgaccagc ctgtttgagg tgctgcctca gcaagtgacc attgatgcca tcagagaggt 2640
ggaaaccctg cctagaaagt acaagaaaga gtgtgaagag gaagccatca acatccagag 2700
cacagcccct gaagaggaac atgagagccc cagagctgag acacccagca cagtgacaga 2760
ggtggacatg gacctggaca gctaccagat tgccctggaa gaggtgctga cctggctgct 2820
gtctgctgag gacaccttcc aagagcagga tgacatctct gatgatgtgg aagaagtgaa 2880
ggaccagttt gccacacatg aggctttcat gatggaactg acagcccacc agtcctctgt 2940
gggctctgtt ctgcaagctg gaaaccagct gatcacccag ggcaccctga gtgatgagga 3000
agagtttgag atccaagaac agatgaccct gctgaatgcc agatgggaag ccctgagagt 3060
ggaatccatg gacagacaga gcagactgca tgatgtgctc atggaactgc agaaaaagca 3120
gctgcagcaa ctgtctgcct ggctgacact gacagaagaa aggatccaga agatggaaac 3180
ctgtccactg gatgatgatg ttaagagcct gcagaagctc ctggaagaac acaagtccct 3240
gcagtctgac ctggaagctg agcaagtcaa agtgaacagc ctgacacaca tggtggtcat 3300
agtggatgag aactctgggg agtctgccac agccattctg gaagatcagc tccagaaact 3360
gggagaaaga tggacagctg tgtgcagatg gactgaggaa aggtggaaca gactgcaaga 3420
gatcaatatc ctgtggcaag agctgcttga ggaacagtgc ctgctgaaag cttggctgac 3480
tgagaaagaa gaggctctga acaaggtgca gaccagcaac ttcaaggacc agaaagaact 3540
gtctgtgtct gtcagaaggc tggccatcct gaaagaggac atggaaatga agagacagac 3600
cctggaccag ctgtctgaga ttggccagga tgtgggccag cttctggaca actctaaggc 3660
cagcaagaag atcaactctg actctgagga actgacccag agatgggact ccctggtgca 3720
gaggctggaa gatagcagca atcaagtgac ccaggctgtg gccaagctgg gcatgtctca 3780
gatccctcag aaggatctgc tggaaacagt tagagttaga gagcaggcca tcaccaagaa 3840
gtccaagcaa gaactggaag ccagctctga ccagtggaag aggctgcacc tgagcctcca 3900
agaactgctt gtgtggctgc agctcaagga tgatgagctg agcagacagg cccctattgg 3960
tggagacttc cctgctgtgc agaaacagaa tgatgtccac agggccttca agagggaact 4020
caagaccaaa gaacctgtga tcatgagcac cctggaaact gtcagaatct tcctgactga 4080
gcagcccctg gaaggactgg aaaagctgta ccaagagcct agagagctgc ctcctgaaga 4140
aagggcccag aatgtgacaa gactgctgag aaagcaggct gaggaagtga acactgagtg 4200
ggagaagctg aatctgcact ctgctgactg gcagagaaag atagatgaga cactggaaag 4260
gctccaagag ttgcaagagg ccacagatga gctggatctg aaactgagac aggctgaagt 4320
gatcaaaggc agctggcagc ctgtgggaga tctgctgatt gacagcctgc aggaccacct 4380
ggaaaaagtc aaggccctga ggggagagat tgcccctctg aaagaaaatg tgtcccatgt 4440
gaatgacctg gccagacagc tcaccacact gggcattcaa ctgagcccct acaacctgtc 4500
tacccttgag gacctgaaca ccagatggaa gctgctccag gtggcagttg aggacagagt 4560
tagacagctg catgaggctc acagagactt tggccctgcc agccagcact tcctgagcac 4620
ctctgtgcaa ggcccttggg agagagctat cagccccaac aaagtgccct actacatcaa 4680
ccatgagact cagaccacct gttgggatca ccccaagatg acagagctgt atcagagcct 4740
ggcagacctc aacaatgtca gattcagtgc ctacaggaca gccatgaagc tgagaaggct 4800
ccagaaggcc ctctgcctgg atctcctgtc tctgtctgca gcttgtgatg ccctggatca 4860
gcacaacctg aagcagaatg atcagcccat ggacatcctg cagatcatca actgcctgac 4920
cacaatctat gacaggctgg aacaagagca caacaacctg gtcaatgtgc ccctgtgtgt 4980
ggacatgtgc ctgaattggc tgctcaatgt gtatgacaca ggcaggacag gcagaatcag 5040
ggtgctgagc ttcaagacag gcatcatcag cctgtgcaaa gctcacttgg aggacaagta 5100
cagatacctg ttcaaacagg tggccagcag cacaggcttt tgtgaccaga gaaggcttgg 5160
cctgctgctg catgacagca ttcagatccc caggcagctt ggagaggtgg cctcctttgg 5220
aggcagcaat attgagccct ctgtcaggtc ctgtttccaa tttgccaaca acaagcctga 5280
gattgaggct gccctgttcc tggactggat gagacttgag ccccagtcca tggtctggct 5340
gccagtgctg catagagtgg ctgctgcaga gacagccaag caccaggcca aatgcaacat 5400
ctgcaaagag tgccccatca ttggcttcag atacagaagc ctgaagcact tcaactatga 5460
tatctgccag agctgtttct ttagtggcag agtggccaag ggccacaaga tgcactaccc 5520
catggtggaa tactgcaccc ctaccacctc tggggaagat gttagagatt ttgccaaggt 5580
gctgaagaac aagttcagga ccaagagata ctttgctaag caccccagga tgggctatct 5640
gcctgtgcag acagtgcttg agggagacaa catggaaaca tgatgaggag ctcgagaggc 5700
ctaataaaga gctcagatgc atcgatcaga gtgtgttggt tttttgtgtg agatctagga 5760
acccctagtg atggagttgg ccactccctc tctgcgcgct cgctcgctca ctgaggccgc 5820
ccgggcaaag cccgggcgtc gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc 5880
gcgcagagag ggagtggcca accccccccc ccccccccct gcaggcgatt ctcttgtttg 5940
ctccagactc tcaggcaatg acctgatagc ctttgtagag acctctcaaa aatagctacc 6000
ctctccggca tgaatttatc agctagaacg gttgaatatc atattgatgg tgatttgact 6060
gtctccggcc tttctcaccc gtttgaatct ttacctacac attactcagg cattgcattt 6120
aaaatatatg agggttctaa aaatttttat ccttgcgttg aaataaaggc ttctcccgca 6180
aaagtattac agggtcataa tgtttttggt acaaccgatt tagctttatg ctctgaggct 6240
ttattgctta attttgctaa ttctttgcct tgcctgtatg atttattgga tgttggaatc 6300
gcctgatgcg gtattttctc cttacgcatc tgtgcggtat ttcacaccgc atatggtgca 6360
ctctcagtac aatctgctct gatgccgcat agttaagcca gccccgacac ccgccaacac 6420
ccgctgacgc gccctgacgg gcttgtctgc tcccggcatc cgcttacaga caagctgtga 6480
ccgtctccgg gagctgcatg tgtcagaggt tttcaccgtc atcaccgaaa cgcgcgagac 6540
gaaagggcct cgtgatacgc ctatttttat aggttaatgt catgataata atggtttctt 6600
agacgtcagg tggcactttt cggggaaatg tgcgcggaac ccctatttgt ttatttttct 6660
aaatacattc aaatatgtat ccgctcatga gacaataacc ctgataaatg cttcaataat 6720
attgaaaaag gaagagtatg attgaacaag atggattgca cgcaggttct ccggccgctt 6780
gggtggagag gctattcggc tatgactggg cacaacagac aatcggctgc tctgatgccg 6840
ccgtgttccg gctgtcagcg caggggcgcc cggttctttt tgtcaagacc gacctgtccg 6900
gtgccctgaa tgaactgcaa gacgaggcag cgcggctatc gtggctggcc acgacgggcg 6960
ttccttgcgc agctgtgctc gatgttgtca ctgaagcggg aagggactgg ctgctattgg 7020
gcgaagtgcc ggggcaggat ctcctgtcat ctcaccttgc tcctgccgag aaagtatcca 7080
tcatggctga tgcaatgcgg cggctgcata cgcttgatcc ggctacctgc ccattcgacc 7140
accaagcgaa acatcgcatc gagcgagcac gtactcggat ggaagccggt cttgtcgatc 7200
aggatgatct ggacgaagag catcaggggc tcgcgccagc cgaactgttc gccaggctca 7260
aggcgagcat gcccgacggc gaggatctcg tcgtgaccca tggcgatgcc tgcttgccga 7320
atatcatggt ggaaaatggc cgcttttctg gattcatcga ctgtggccgg ctgggtgtgg 7380
cggaccgcta tcaggacata gcgttggcta cccgtgatat tgctgaagag cttggcggcg 7440
aatgggctga ccgcttcctc gtgctttacg gtatcgccgc tcccgattcg cagcgcatcg 7500
ccttctatcg ccttcttgac gagttcttct gactgtcaga ccaagtttac tcatatatac 7560
tttagattga tttaaaactt catttttaat ttaaaaggat ctaggtgaag atcctttttg 7620
ataatctcat gaccaaaatc ccttaacgtg agttttcgtt ccactgagcg tcagaccccg 7680
tagaaaagat caaaggatct tcttgagatc ctttttttct gcgcgtaatc tgctgcttgc 7740
aaacaaaaaa accaccgcta ccagcggtgg tttgtttgcc ggatcaagag ctaccaactc 7800
tttttccgaa ggtaactggc ttcagcagag cgcagatacc aaatactgtt cttctagtgt 7860
agccgtagtt aggccaccac ttcaagaact ctgtagcacc gcctacatac ctcgctctgc 7920
taatcctgtt accagtggct gctgccagtg gcgataagtc gtgtcttacc gggttggact 7980
caagacgata gttaccggat aaggcgcagc ggtcgggctg aacggggggt tcgtgcacac 8040
agcccagctt ggagcgaacg acctacaccg aactgagata cctacagcgt gagctatgag 8100
aaagcgccac gcttcccgaa gggagaaagg cggacaggta tccggtaagc ggcagggtcg 8160
gaacaggaga gcgcacgagg gagcttccag ggggaaacgc ctggtatctt tatagtcctg 8220
tcgggtttcg ccacctctga cttgagcgtc gatttttgtg atgctcgtca ggggggcgga 8280
gcctatggaa aaacgccagc aacgcggcct ttttacggtt cctggccttt tgctggcctt 8340
ttgctcacat gttctttcct gcgttatccc ctgattctgt ggataaccgt attaccgcct 8400
ttgagtgagc tgataccgct cgccgcagcc gaacgaccga gcgcagcgag tcagtgagcg 8460
aggaagcgga agagcgccca atacgcaaac cgcctctccc cgcgcgttgg ccgattcatt 8520
aatgcagaat tcccatcatc aataatatac cttattttgg attgaagcca atatgataat 8580
gagggggtgg agtttgtgac gtggcgcggg gcgtgggaac ggggcgggtg acgtagtagc 8640
t 8641
<210> 7
<211> 8641
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> shCK-M6表达盒的核苷酸序列
<400> 7
ctagaggtcc ccagcgacct tgacgagcat ctgcccggca tttctgacag ctttgtgaac 60
tgggtggccg agaaggaatg ggagttgccg ccagattctg acatggatct gaatctgatt 120
gagcaggcac ccctgaccgt ggccgagaag ctgcatcgct ggcgtaatag cgaagaggcc 180
cgcaccgatc gcccttccca acagttgcgc agcctgaatg gcgaatggcg attccgttgc 240
aatggctggc ggtaatattg ttctggatat taccagcaag gccgatagtt tgagttcttc 300
tactcaggca agtgatgtta ttactaatca aagaagtatt gcgacaacgg ttaatttgcg 360
tgatggacag actcttttac tcggtggcct cactgattat aaaaacactt ctcaggattc 420
tggcgtaccg ttcctgtcta aaatcccttt aatcggcctc ctgtttagct cccgctctga 480
ttctaacgag gaaagcacgt tatacgtgct cgtcaaagca accatagtac gcgccctgta 540
gcggcgcatt aagcgcggcg ggtgtggtgg ttacgcgcag cgtgaccgct acacttgcca 600
gcgccctagc gcccgctcct ttcgctttct tcccttcctt tctcgccacg ttcgccggct 660
ttccccgtca agctctaaat cgggggctcc ctttagggtt ccgatttagt gctttacggc 720
acctcgaccc caaaaaactt gattagggtg atggttcacg tagtgggcca tcgccctgat 780
agacggtttt tcgccctttg acgttggagt ccacgttctt aatagtggac tcttgttcca 840
aactggaaca acactcaacc ctatctcggt ctattctttt gatttataag ggattttgcc 900
gatttcggcc tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattttaa 960
caaaatatta acgcttacaa tttaaatatt tgcttataca atcttcctgt ttttggggct 1020
tttctgatta tcaaccgggg tacatatgat tgacatgcta gttttacgat taccgttcat 1080
cgcctgcagg gggggggggg ggggggttgg ccactccctc tctgcgcgct cgctcgctca 1140
ctgaggccgg gcgaccaaag gtcgcccgac gcccgggctt tgcccgggcg gcctcagtga 1200
gcgagcgagc gcgcagagag ggagtggcca actccatcac taggggttcc tagatctgaa 1260
ttcggtaccc cactacgggt ttaggctgcc catgtaagga ggcaaggcct ggggacaccc 1320
gagatgcctg gttataatta acccagacat gtggctgccc cccccccccc caacacctgc 1380
tgcctctaaa aataaccctg tccctggtgg atcccctgca tgcgaagatc ttcgaacaag 1440
gctgtggggg actgagggca ggctgtaaca ggcttggggg ccagggctta tacgtgcctg 1500
ggactcccaa agtattactg ttccatgttc ccggcgaagg gccagctgtc ccccgccagc 1560
tagactcagc acttagttta ggaaccagtg agcaagtcag cccttggggc agcccataca 1620
aggccatggg gctgggcaag ctgcacgcct gggtccgggg tgggcacggt gcccgggcaa 1680
cgagctgaaa gctcatctgc tctcaggggc ccctccctgg ggacagcccc tcctggctag 1740
tcacaccctg taggctcctc tatataaccc aggggcacag gggctgccct cattctacca 1800
ccaccacagc acagacagac aaaactccta aaaaaccgcc accatggcca aatatggcga 1860
gcatgaggct agccccgaca acggccagaa cgagttcagc gacatcatca agagcagaag 1920
cgacgagcac aacgacgtgc agaagaaaac cttcaccaag tggatcaacg cccggttcag 1980
caagagcggc aagcctccta tcaacgacat gttcaccgac ctgaaggacg gcagaaagct 2040
gctggatctg ctggaaggcc tgaccggcac aagcctgcct aaagaaaggg gcagcacaag 2100
agtgcacgcc ctgaacaacg tgaaccgggt gctgcaggtt ctgcaccaga acaatgtgga 2160
actggtcaac atcggcggca ccgacatcgt ggacggcaat cacaaactga ccctgggcct 2220
gctgtggtcc atcatcctgc actggcaagt gaaagacgtg atgaaggatg tgatgagcga 2280
tctgcagcag accaacagcg agaagatcct gctgagctgg gtccgacaga ccaccagacc 2340
ttacagccaa gtgaacgtgc tgaacttcac caccagctgg acagacggcc tggcctttaa 2400
tgccgtgctg cacagacaca agcccgacct gttcagctgg gacaaagtgg tcaagatgag 2460
ccccatcgag cggctggaac acgccttttc taaggcccag acctacctgg gcatcgaaaa 2520
actgctggac cccgaggatg tggccgtgca gctgcctgac aagaaatcca tcatcatgta 2580
cctgaccagc ctgttcgagg tgctgcctca gcaagtgacc atcgacgcca tcagagaggt 2640
ggaaaccctg cctcggaagt acaagaaaga gtgcgaggaa gaggccatca acatccagag 2700
cacagcccct gaggaagaac acgagagccc tagagccgag acacctagca cagtgaccga 2760
ggtggacatg gacctggaca gctatcagat cgccctggaa gaggtgctga cctggctgct 2820
gtctgccgag gataccttcc aagagcagga cgacatcagc gacgacgtgg aagaagtgaa 2880
ggaccagttc gccacacacg aggccttcat gatggaactg acagcccacc agtctagcgt 2940
gggctctgtt ctgcaagccg gcaaccagct gatcacccag ggcaccctgt ctgatgagga 3000
agagttcgag atccaagaac agatgaccct gctgaacgcc agatgggaag ccctgagagt 3060
ggaatccatg gaccggcaga gcagactgca cgacgtgctc atggaactgc agaaaaagca 3120
gctgcagcag ctcagcgcct ggctgacact gaccgaagaa cggatccaga agatggaaac 3180
ctgtcctctg gacgacgatg tgaagtccct gcagaagctg ctcgaggaac acaagagcct 3240
gcagagcgac ctggaagccg agcaagtcaa agtgaacagc ctgacacaca tggtcgtgat 3300
cgtggatgag aacagcggcg agtctgccac agccatcctg gaagatcagc tgcagaaact 3360
gggcgagaga tggaccgccg tgtgcagatg gacagaggaa cggtggaacc ggctgcaaga 3420
gatcaatatc ctgtggcaag aactcctcga agaacagtgt ctgctgaagg cttggctgac 3480
cgagaaagaa gaggctctga acaaggtgca gaccagcaac ttcaaggacc agaaagaact 3540
gagcgtgtcc gtgcggagac tggccattct gaaagaggac atggaaatga agcggcagac 3600
cctggaccag ctgtctgaga tcggacagga tgtgggccag ctcctggaca atagcaaggc 3660
cagcaagaag atcaacagcg acagcgagga actgacccag agatgggatt cactggtgca 3720
gcggctcgag gacagcagca atcaagtgac acaggccgtg gccaagctgg gcatgtctca 3780
gatccctcag aaggacctgc tggaaaccgt cagagtcaga gagcaggcca tcaccaagaa 3840
gtccaagcaa gaactggaag ccagctccga ccagtggaag agactgcacc tgtctctgca 3900
agagctgctc gtgtggctgc agctcaagga cgatgagctg agcagacagg cccctatcgg 3960
cggagatttt cccgccgtgc agaaacagaa cgatgtgcac cgggccttca agcgcgagct 4020
gaaaacaaaa gaacccgtga tcatgagcac cctggaaaca gtgcggatct tcctgaccga 4080
gcagcccctg gaaggactgg aaaagctgta ccaagagcct agagagctgc ctcctgaaga 4140
acgggcccag aacgtgacca gactgctgag aaagcaggcc gaggaagtga acaccgagtg 4200
ggagaagctg aacctgcaca gcgccgactg gcagcggaag attgacgaga cactggaaag 4260
actccaagaa ctgcaagagg ccaccgacga gctggacctg aaactgagac aggccgaagt 4320
gatcaaaggc agctggcagc ctgtgggcga cctgctgatt gatagcctgc aggaccacct 4380
cgagaaagtg aaggctctga gaggcgagat cgcccctctg aaagaaaacg tgtcccacgt 4440
gaacgacctg gctcggcagc tgacaacact gggaattcag ctgagcccct acaacctgtc 4500
cacactcgag gacctgaaca cccggtggaa actgcttcag gtggccgtgg aagatagagt 4560
gcgccagctg catgaggccc acagagattt tggacctgcc agccagcact tcctgagcac 4620
ctctgtgcaa ggcccttggg agagagctat cagccccaac aaagtgccct actacatcaa 4680
ccacgagaca cagaccacat gctgggatca ccccaagatg accgagctgt atcagagcct 4740
ggccgacctc aacaacgtgc ggtttagcgc ctaccggacc gccatgaagc tgcggaggct 4800
gcaaaaagcc ctgtgcctgg atctcctgag cctgagcgct gcttgtgatg ccctggatca 4860
gcacaatctg aagcagaacg accagcctat ggacatcctg cagatcatca actgcctgac 4920
caccatctac gaccgcctgg aacaagagca caacaacctg gtcaacgtgc ccctgtgcgt 4980
ggacatgtgc ctgaattggc tgctgaatgt gtacgacacc ggcagaaccg gcaggatcag 5040
agtgctgagc ttcaagaccg gcatcatcag cctgtgcaaa gcccaccttg aggacaagta 5100
ccgctacctg ttcaaacagg tggccagcag caccggcttt tgcgaccaaa gaaggctggg 5160
actgctgctg cacgacagca ttcagatccc acggcagctg ggagaagtgg ccagctttgg 5220
cggcagcaat atcgagccta gcgtgcggtc ctgctttcag tttgccaaca acaagcctga 5280
gatcgaggcc gctctgttcc tggactggat gagactggaa ccccagagca tggtctggct 5340
gcctgtgctg catagagtgg ctgccgccga aacagccaag caccaggcca agtgcaacat 5400
ctgcaaagag tgccccatca tcggcttccg gtacagaagc ctgaagcact tcaactacga 5460
tatctgccag tcctgcttct tcagcggcag agtggccaag ggccacaaga tgcactaccc 5520
catggtggaa tactgcaccc ctaccaccag cggagaggac gtgcgggatt ttgccaaggt 5580
gctgaagaac aagttccgga ccaagcgcta cttcgctaag caccccagaa tgggctatct 5640
gcccgtgcag acagtcctgg aaggcgacaa catggaaacc tgatgaggag ctcgagaggc 5700
ctaataaaga gctcagatgc atcgatcaga gtgtgttggt tttttgtgtg agatctagga 5760
acccctagtg atggagttgg ccactccctc tctgcgcgct cgctcgctca ctgaggccgc 5820
ccgggcaaag cccgggcgtc gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc 5880
gcgcagagag ggagtggcca accccccccc ccccccccct gcaggcgatt ctcttgtttg 5940
ctccagactc tcaggcaatg acctgatagc ctttgtagag acctctcaaa aatagctacc 6000
ctctccggca tgaatttatc agctagaacg gttgaatatc atattgatgg tgatttgact 6060
gtctccggcc tttctcaccc gtttgaatct ttacctacac attactcagg cattgcattt 6120
aaaatatatg agggttctaa aaatttttat ccttgcgttg aaataaaggc ttctcccgca 6180
aaagtattac agggtcataa tgtttttggt acaaccgatt tagctttatg ctctgaggct 6240
ttattgctta attttgctaa ttctttgcct tgcctgtatg atttattgga tgttggaatc 6300
gcctgatgcg gtattttctc cttacgcatc tgtgcggtat ttcacaccgc atatggtgca 6360
ctctcagtac aatctgctct gatgccgcat agttaagcca gccccgacac ccgccaacac 6420
ccgctgacgc gccctgacgg gcttgtctgc tcccggcatc cgcttacaga caagctgtga 6480
ccgtctccgg gagctgcatg tgtcagaggt tttcaccgtc atcaccgaaa cgcgcgagac 6540
gaaagggcct cgtgatacgc ctatttttat aggttaatgt catgataata atggtttctt 6600
agacgtcagg tggcactttt cggggaaatg tgcgcggaac ccctatttgt ttatttttct 6660
aaatacattc aaatatgtat ccgctcatga gacaataacc ctgataaatg cttcaataat 6720
attgaaaaag gaagagtatg attgaacaag atggattgca cgcaggttct ccggccgctt 6780
gggtggagag gctattcggc tatgactggg cacaacagac aatcggctgc tctgatgccg 6840
ccgtgttccg gctgtcagcg caggggcgcc cggttctttt tgtcaagacc gacctgtccg 6900
gtgccctgaa tgaactgcaa gacgaggcag cgcggctatc gtggctggcc acgacgggcg 6960
ttccttgcgc agctgtgctc gatgttgtca ctgaagcggg aagggactgg ctgctattgg 7020
gcgaagtgcc ggggcaggat ctcctgtcat ctcaccttgc tcctgccgag aaagtatcca 7080
tcatggctga tgcaatgcgg cggctgcata cgcttgatcc ggctacctgc ccattcgacc 7140
accaagcgaa acatcgcatc gagcgagcac gtactcggat ggaagccggt cttgtcgatc 7200
aggatgatct ggacgaagag catcaggggc tcgcgccagc cgaactgttc gccaggctca 7260
aggcgagcat gcccgacggc gaggatctcg tcgtgaccca tggcgatgcc tgcttgccga 7320
atatcatggt ggaaaatggc cgcttttctg gattcatcga ctgtggccgg ctgggtgtgg 7380
cggaccgcta tcaggacata gcgttggcta cccgtgatat tgctgaagag cttggcggcg 7440
aatgggctga ccgcttcctc gtgctttacg gtatcgccgc tcccgattcg cagcgcatcg 7500
ccttctatcg ccttcttgac gagttcttct gactgtcaga ccaagtttac tcatatatac 7560
tttagattga tttaaaactt catttttaat ttaaaaggat ctaggtgaag atcctttttg 7620
ataatctcat gaccaaaatc ccttaacgtg agttttcgtt ccactgagcg tcagaccccg 7680
tagaaaagat caaaggatct tcttgagatc ctttttttct gcgcgtaatc tgctgcttgc 7740
aaacaaaaaa accaccgcta ccagcggtgg tttgtttgcc ggatcaagag ctaccaactc 7800
tttttccgaa ggtaactggc ttcagcagag cgcagatacc aaatactgtt cttctagtgt 7860
agccgtagtt aggccaccac ttcaagaact ctgtagcacc gcctacatac ctcgctctgc 7920
taatcctgtt accagtggct gctgccagtg gcgataagtc gtgtcttacc gggttggact 7980
caagacgata gttaccggat aaggcgcagc ggtcgggctg aacggggggt tcgtgcacac 8040
agcccagctt ggagcgaacg acctacaccg aactgagata cctacagcgt gagctatgag 8100
aaagcgccac gcttcccgaa gggagaaagg cggacaggta tccggtaagc ggcagggtcg 8160
gaacaggaga gcgcacgagg gagcttccag ggggaaacgc ctggtatctt tatagtcctg 8220
tcgggtttcg ccacctctga cttgagcgtc gatttttgtg atgctcgtca ggggggcgga 8280
gcctatggaa aaacgccagc aacgcggcct ttttacggtt cctggccttt tgctggcctt 8340
ttgctcacat gttctttcct gcgttatccc ctgattctgt ggataaccgt attaccgcct 8400
ttgagtgagc tgataccgct cgccgcagcc gaacgaccga gcgcagcgag tcagtgagcg 8460
aggaagcgga agagcgccca atacgcaaac cgcctctccc cgcgcgttgg ccgattcatt 8520
aatgcagaat tcccatcatc aataatatac cttattttgg attgaagcca atatgataat 8580
gagggggtgg agtttgtgac gtggcgcggg gcgtgggaac ggggcgggtg acgtagtagc 8640
t 8641
<210> 8
<211> 3840
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 密码子优化的M6(opti-M6)构建体的核苷酸序列
<400> 8
atggccaaat atggggagca tgaggcctct ccagacaatg gccagaatga gttctctgac 60
atcatcaaga gcagatctga tgagcacaat gatgtgcaga agaaaacctt caccaagtgg 120
atcaatgcca ggttcagcaa gtctggcaag cctcctatca atgacatgtt cacagacctg 180
aaggatggca gaaagctgct ggacctgctg gaaggcctga caggcacaag cctgcctaaa 240
gaaaggggca gcaccagagt gcatgccctg aacaatgtga acagagtgct gcaggtcctg 300
caccagaaca atgttgagct ggtcaatatt ggaggcacag acattgtgga tggcaaccac 360
aagctgaccc tgggcctgct gtggtccatc atcctgcact ggcaagtgaa agatgtgatg 420
aaggatgtca tgtctgacct ccagcagacc aactctgaga agatcctgct gagctgggtc 480
agacagacca ccagacctta cagccaagtg aatgtgctga acttcaccac cagctggaca 540
gatggcctgg ccttcaatgc tgtgctgcac agacacaagc cagacctgtt cagctgggac 600
aaagtggtca agatgagccc cattgagaga ctggaacatg ccttcagcaa ggcccagacc 660
tacctgggca ttgaaaaact gctggatcct gaggatgtgg cagtgcagct gcctgacaag 720
aaatccatca tcatgtacct gaccagcctg tttgaggtgc tgcctcagca agtgaccatt 780
gatgccatca gagaggtgga aaccctgcct agaaagtaca agaaagagtg tgaagaggaa 840
gccatcaaca tccagagcac agcccctgaa gaggaacatg agagccccag agctgagaca 900
cccagcacag tgacagaggt ggacatggac ctggacagct accagattgc cctggaagag 960
gtgctgacct ggctgctgtc tgctgaggac accttccaag agcaggatga catctctgat 1020
gatgtggaag aagtgaagga ccagtttgcc acacatgagg ctttcatgat ggaactgaca 1080
gcccaccagt cctctgtggg ctctgttctg caagctggaa accagctgat cacccagggc 1140
accctgagtg atgaggaaga gtttgagatc caagaacaga tgaccctgct gaatgccaga 1200
tgggaagccc tgagagtgga atccatggac agacagagca gactgcatga tgtgctcatg 1260
gaactgcaga aaaagcagct gcagcaactg tctgcctggc tgacactgac agaagaaagg 1320
atccagaaga tggaaacctg tccactggat gatgatgtta agagcctgca gaagctcctg 1380
gaagaacaca agtccctgca gtctgacctg gaagctgagc aagtcaaagt gaacagcctg 1440
acacacatgg tggtcatagt ggatgagaac tctggggagt ctgccacagc cattctggaa 1500
gatcagctcc agaaactggg agaaagatgg acagctgtgt gcagatggac tgaggaaagg 1560
tggaacagac tgcaagagat caatatcctg tggcaagagc tgcttgagga acagtgcctg 1620
ctgaaagctt ggctgactga gaaagaagag gctctgaaca aggtgcagac cagcaacttc 1680
aaggaccaga aagaactgtc tgtgtctgtc agaaggctgg ccatcctgaa agaggacatg 1740
gaaatgaaga gacagaccct ggaccagctg tctgagattg gccaggatgt gggccagctt 1800
ctggacaact ctaaggccag caagaagatc aactctgact ctgaggaact gacccagaga 1860
tgggactccc tggtgcagag gctggaagat agcagcaatc aagtgaccca ggctgtggcc 1920
aagctgggca tgtctcagat ccctcagaag gatctgctgg aaacagttag agttagagag 1980
caggccatca ccaagaagtc caagcaagaa ctggaagcca gctctgacca gtggaagagg 2040
ctgcacctga gcctccaaga actgcttgtg tggctgcagc tcaaggatga tgagctgagc 2100
agacaggccc ctattggtgg agacttccct gctgtgcaga aacagaatga tgtccacagg 2160
gccttcaaga gggaactcaa gaccaaagaa cctgtgatca tgagcaccct ggaaactgtc 2220
agaatcttcc tgactgagca gcccctggaa ggactggaaa agctgtacca agagcctaga 2280
gagctgcctc ctgaagaaag ggcccagaat gtgacaagac tgctgagaaa gcaggctgag 2340
gaagtgaaca ctgagtggga gaagctgaat ctgcactctg ctgactggca gagaaagata 2400
gatgagacac tggaaaggct ccaagagttg caagaggcca cagatgagct ggatctgaaa 2460
ctgagacagg ctgaagtgat caaaggcagc tggcagcctg tgggagatct gctgattgac 2520
agcctgcagg accacctgga aaaagtcaag gccctgaggg gagagattgc ccctctgaaa 2580
gaaaatgtgt cccatgtgaa tgacctggcc agacagctca ccacactggg cattcaactg 2640
agcccctaca acctgtctac ccttgaggac ctgaacacca gatggaagct gctccaggtg 2700
gcagttgagg acagagttag acagctgcat gaggctcaca gagactttgg ccctgccagc 2760
cagcacttcc tgagcacctc tgtgcaaggc ccttgggaga gagctatcag ccccaacaaa 2820
gtgccctact acatcaacca tgagactcag accacctgtt gggatcaccc caagatgaca 2880
gagctgtatc agagcctggc agacctcaac aatgtcagat tcagtgccta caggacagcc 2940
atgaagctga gaaggctcca gaaggccctc tgcctggatc tcctgtctct gtctgcagct 3000
tgtgatgccc tggatcagca caacctgaag cagaatgatc agcccatgga catcctgcag 3060
atcatcaact gcctgaccac aatctatgac aggctggaac aagagcacaa caacctggtc 3120
aatgtgcccc tgtgtgtgga catgtgcctg aattggctgc tcaatgtgta tgacacaggc 3180
aggacaggca gaatcagggt gctgagcttc aagacaggca tcatcagcct gtgcaaagct 3240
cacttggagg acaagtacag atacctgttc aaacaggtgg ccagcagcac aggcttttgt 3300
gaccagagaa ggcttggcct gctgctgcat gacagcattc agatccccag gcagcttgga 3360
gaggtggcct cctttggagg cagcaatatt gagccctctg tcaggtcctg tttccaattt 3420
gccaacaaca agcctgagat tgaggctgcc ctgttcctgg actggatgag acttgagccc 3480
cagtccatgg tctggctgcc agtgctgcat agagtggctg ctgcagagac agccaagcac 3540
caggccaaat gcaacatctg caaagagtgc cccatcattg gcttcagata cagaagcctg 3600
aagcacttca actatgatat ctgccagagc tgtttcttta gtggcagagt ggccaagggc 3660
cacaagatgc actaccccat ggtggaatac tgcaccccta ccacctctgg ggaagatgtt 3720
agagattttg ccaaggtgct gaagaacaag ttcaggacca agagatactt tgctaagcac 3780
cccaggatgg gctatctgcc tgtgcagaca gtgcttgagg gagacaacat ggaaacatga 3840
<210> 9
<211> 580
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> shCK启动子的核苷酸序列
<400> 9
gaattcggta ccccactacg ggtttaggct gcccatgtaa ggaggcaagg cctggggaca 60
cccgagatgc ctggttataa ttaacccaga catgtggctg cccccccccc ccccaacacc 120
tgctgcctct aaaaataacc ctgtccctgg tggatcccct gcatgcgaag atcttcgaac 180
aaggctgtgg gggactgagg gcaggctgta acaggcttgg gggccagggc ttatacgtgc 240
ctgggactcc caaagtatta ctgttccatg ttcccggcga agggccagct gtcccccgcc 300
agctagactc agcacttagt ttaggaacca gtgagcaagt cagcccttgg ggcagcccat 360
acaaggccat ggggctgggc aagctgcacg cctgggtccg gggtgggcac ggtgcccggg 420
caacgagctg aaagctcatc tgctctcagg ggcccctccc tggggacagc ccctcctggc 480
tagtcacacc ctgtaggctc ctctatataa cccaggggca caggggctgc cctcattcta 540
ccaccaccac agcacagaca gacaaaactc ctaaaaaacc 580
<210> 10
<211> 3840
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 未经密码子优化的M6构建体的核苷酸序列
<400> 10
atggccaaat atggcgagca tgaggctagc cccgacaacg gccagaacga gttcagcgac 60
atcatcaaga gcagaagcga cgagcacaac gacgtgcaga agaaaacctt caccaagtgg 120
atcaacgccc ggttcagcaa gagcggcaag cctcctatca acgacatgtt caccgacctg 180
aaggacggca gaaagctgct ggatctgctg gaaggcctga ccggcacaag cctgcctaaa 240
gaaaggggca gcacaagagt gcacgccctg aacaacgtga accgggtgct gcaggttctg 300
caccagaaca atgtggaact ggtcaacatc ggcggcaccg acatcgtgga cggcaatcac 360
aaactgaccc tgggcctgct gtggtccatc atcctgcact ggcaagtgaa agacgtgatg 420
aaggatgtga tgagcgatct gcagcagacc aacagcgaga agatcctgct gagctgggtc 480
cgacagacca ccagacctta cagccaagtg aacgtgctga acttcaccac cagctggaca 540
gacggcctgg cctttaatgc cgtgctgcac agacacaagc ccgacctgtt cagctgggac 600
aaagtggtca agatgagccc catcgagcgg ctggaacacg ccttttctaa ggcccagacc 660
tacctgggca tcgaaaaact gctggacccc gaggatgtgg ccgtgcagct gcctgacaag 720
aaatccatca tcatgtacct gaccagcctg ttcgaggtgc tgcctcagca agtgaccatc 780
gacgccatca gagaggtgga aaccctgcct cggaagtaca agaaagagtg cgaggaagag 840
gccatcaaca tccagagcac agcccctgag gaagaacacg agagccctag agccgagaca 900
cctagcacag tgaccgaggt ggacatggac ctggacagct atcagatcgc cctggaagag 960
gtgctgacct ggctgctgtc tgccgaggat accttccaag agcaggacga catcagcgac 1020
gacgtggaag aagtgaagga ccagttcgcc acacacgagg ccttcatgat ggaactgaca 1080
gcccaccagt ctagcgtggg ctctgttctg caagccggca accagctgat cacccagggc 1140
accctgtctg atgaggaaga gttcgagatc caagaacaga tgaccctgct gaacgccaga 1200
tgggaagccc tgagagtgga atccatggac cggcagagca gactgcacga cgtgctcatg 1260
gaactgcaga aaaagcagct gcagcagctc agcgcctggc tgacactgac cgaagaacgg 1320
atccagaaga tggaaacctg tcctctggac gacgatgtga agtccctgca gaagctgctc 1380
gaggaacaca agagcctgca gagcgacctg gaagccgagc aagtcaaagt gaacagcctg 1440
acacacatgg tcgtgatcgt ggatgagaac agcggcgagt ctgccacagc catcctggaa 1500
gatcagctgc agaaactggg cgagagatgg accgccgtgt gcagatggac agaggaacgg 1560
tggaaccggc tgcaagagat caatatcctg tggcaagaac tcctcgaaga acagtgtctg 1620
ctgaaggctt ggctgaccga gaaagaagag gctctgaaca aggtgcagac cagcaacttc 1680
aaggaccaga aagaactgag cgtgtccgtg cggagactgg ccattctgaa agaggacatg 1740
gaaatgaagc ggcagaccct ggaccagctg tctgagatcg gacaggatgt gggccagctc 1800
ctggacaata gcaaggccag caagaagatc aacagcgaca gcgaggaact gacccagaga 1860
tgggattcac tggtgcagcg gctcgaggac agcagcaatc aagtgacaca ggccgtggcc 1920
aagctgggca tgtctcagat ccctcagaag gacctgctgg aaaccgtcag agtcagagag 1980
caggccatca ccaagaagtc caagcaagaa ctggaagcca gctccgacca gtggaagaga 2040
ctgcacctgt ctctgcaaga gctgctcgtg tggctgcagc tcaaggacga tgagctgagc 2100
agacaggccc ctatcggcgg agattttccc gccgtgcaga aacagaacga tgtgcaccgg 2160
gccttcaagc gcgagctgaa aacaaaagaa cccgtgatca tgagcaccct ggaaacagtg 2220
cggatcttcc tgaccgagca gcccctggaa ggactggaaa agctgtacca agagcctaga 2280
gagctgcctc ctgaagaacg ggcccagaac gtgaccagac tgctgagaaa gcaggccgag 2340
gaagtgaaca ccgagtggga gaagctgaac ctgcacagcg ccgactggca gcggaagatt 2400
gacgagacac tggaaagact ccaagaactg caagaggcca ccgacgagct ggacctgaaa 2460
ctgagacagg ccgaagtgat caaaggcagc tggcagcctg tgggcgacct gctgattgat 2520
agcctgcagg accacctcga gaaagtgaag gctctgagag gcgagatcgc ccctctgaaa 2580
gaaaacgtgt cccacgtgaa cgacctggct cggcagctga caacactggg aattcagctg 2640
agcccctaca acctgtccac actcgaggac ctgaacaccc ggtggaaact gcttcaggtg 2700
gccgtggaag atagagtgcg ccagctgcat gaggcccaca gagattttgg acctgccagc 2760
cagcacttcc tgagcacctc tgtgcaaggc ccttgggaga gagctatcag ccccaacaaa 2820
gtgccctact acatcaacca cgagacacag accacatgct gggatcaccc caagatgacc 2880
gagctgtatc agagcctggc cgacctcaac aacgtgcggt ttagcgccta ccggaccgcc 2940
atgaagctgc ggaggctgca aaaagccctg tgcctggatc tcctgagcct gagcgctgct 3000
tgtgatgccc tggatcagca caatctgaag cagaacgacc agcctatgga catcctgcag 3060
atcatcaact gcctgaccac catctacgac cgcctggaac aagagcacaa caacctggtc 3120
aacgtgcccc tgtgcgtgga catgtgcctg aattggctgc tgaatgtgta cgacaccggc 3180
agaaccggca ggatcagagt gctgagcttc aagaccggca tcatcagcct gtgcaaagcc 3240
caccttgagg acaagtaccg ctacctgttc aaacaggtgg ccagcagcac cggcttttgc 3300
gaccaaagaa ggctgggact gctgctgcac gacagcattc agatcccacg gcagctggga 3360
gaagtggcca gctttggcgg cagcaatatc gagcctagcg tgcggtcctg ctttcagttt 3420
gccaacaaca agcctgagat cgaggccgct ctgttcctgg actggatgag actggaaccc 3480
cagagcatgg tctggctgcc tgtgctgcat agagtggctg ccgccgaaac agccaagcac 3540
caggccaagt gcaacatctg caaagagtgc cccatcatcg gcttccggta cagaagcctg 3600
aagcacttca actacgatat ctgccagtcc tgcttcttca gcggcagagt ggccaagggc 3660
cacaagatgc actaccccat ggtggaatac tgcaccccta ccaccagcgg agaggacgtg 3720
cgggattttg ccaaggtgct gaagaacaag ttccggacca agcgctactt cgctaagcac 3780
cccagaatgg gctatctgcc cgtgcagaca gtcctggaag gcgacaacat ggaaacctga 3840
<210> 11
<211> 3978
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> B84的核苷酸序列
<400> 11
atgctttggt gggaggaagt ggaggactgc tacgagagag aggacgtgca gaagaaaacc 60
ttcaccaagt gggtgaacgc ccagttcagc aagttcggca agcagcacat cgagaacctg 120
ttcagcgacc tgcaggatgg caggagactg ctggacctgc tggagggcct gaccggccag 180
aagctgccca aggagaaggg cagcaccaga gtgcacgccc tgaacaacgt gaacaaggcc 240
ctgagagtgc tgcagaacaa caacgtggac ctggtgaaca tcggcagcac cgacatcgtg 300
gacggcaacc acaagctgac cctgggcctg atctggaaca tcatcctgca ctggcaggtg 360
aagaacgtga tgaagaacat catggccggc ctgcagcaga ccaacagcga gaagatcctg 420
ctgagctggg tgaggcagag caccagaaac tacccccagg tgaacgtgat caacttcacc 480
acctcctgga gcgacggcct ggccctgaac gccctgatcc acagccacag acccgacctg 540
ttcgactgga acagcgtggt gtgtcagcag agcgccaccc agagactgga gcacgccttc 600
aacatcgcca gataccagct gggcatcgag aagctgctgg accccgagga cgtggacacc 660
acctaccccg acaagaaaag catcctcatg tacattacca gcctgttcca ggtgctgccc 720
cagcaggtgt ccatcgaggc catccaggaa gtggaaatgc tgcccaggcc ccccaaagtg 780
accaaggagg agcacttcca gctgcaccac cagatgcact acagccagca gatcacagtg 840
agcctggccc agggctatga gagaaccagc agccccaagc ccagattcaa gagctacgcc 900
tacacccagg ccgcctacgt gaccacctcc gaccccacca gaagcccctt ccccagccag 960
cacctggagg cccccgagga caagagcttc ggcagcagcc tgatggagag cgaagtgaac 1020
ctggacagat accagaccgc cctggaggaa gtgctgtcct ggctgctgag cgccgaggac 1080
accctgcagg cccagggcga gatcagcaac gacgtggaag tggtgaagga ccagttccac 1140
acccacgagg gctacatgat ggatctgacc gcccaccagg gcagagtggg caatatcctg 1200
cagctgggca gcaagctgat cggcaccggc aagctgagcg aggacgagga gaccgaagtg 1260
caggagcaga tgaacctgct gaacagcaga tgggagtgcc tgagagtggc cagcatggag 1320
aagcagagca acctgcacag agtgctgatg gacctgcaga accagaagct gaaggagctg 1380
aacgactggc tgaccaagac cgaggagcgg accagaaaga tggaggagga gcccctgggc 1440
cccgacctgg aggacctgaa gagacaggtg cagcagcaca aagtgctgca ggaggacctg 1500
gagcaggagc aggtgcgcgt gaacagcctg acccacatgg tggtggtcgt ggacgagagc 1560
agcggcgacc acgccacagc cgccctggaa gagcagctga aagtgctggg cgacagatgg 1620
gccaatattt gtaggtggac cgaggacaga tgggtgctgc tgcaggacca gcccgacctg 1680
gcccctggcc tgaccaccat cggcgccagc cccacccaga ccgtgaccct ggtgacccag 1740
cccgtggtga caaaggagac cgccatcagc aagctggaga tgcccagctc cctgatgctg 1800
gaagtgccca cccaccgcct gctccagcag ttccccctgg acctggagaa gttcctggcc 1860
tggctgaccg aggccgaaac caccgccaat gtgctccagg acgccactag aaaggagagg 1920
ctgctggagg acagcaaggg cgtgaaagag ctgatgaagc agtggcagga tctgcagggc 1980
gaaatcgagg cccacaccga cgtgtaccac aacctggacg agaacagcca gaagattctg 2040
aggagcctgg agggcagcga cgacgccgtc ctgctccaga ggaggctgga caacatgaac 2100
ttcaagtgga gcgagctgcg gaagaagagc ctgaacatcc ggagccacct ggaagccagc 2160
agcgaccagt ggaagagact gcacctgagc ctgcaggagc tgctggtgtg gctgcagctg 2220
aaggacgacg agctgagcag acaggccccc atcggcggcg acttccccgc cgtgcagaag 2280
cagaacgacg tgcaccgggc cttcaagagg gagctgaaaa ccaaggaacc cgtgatcatg 2340
agcaccctgg agacagtgcg gatcttcctg accgagcagc ccctggaggg actggagaag 2400
ctgtaccagg agcccagaga gctgcccccc gaggagagag cccagaacgt gaccaggctg 2460
ctgagaaagc aggccgagga agtgaatacc gagtgggaga agctgaatct gcacagcgcc 2520
gactggcaga gaaagatcga cgagaccctg gagagactcc aggaactgca ggaagccacc 2580
gacgagctgg acctgaagct gagacaggcc gaagtgatca agggcagctg gcagcctgtg 2640
ggcgatctgc tgatcgactc cctgcaggat cacctggaga aagtgaaggc cctgcggggc 2700
gagatcgccc ccctgaagga gaatgtgagc cacgtgaacg acctggccag acagctgacc 2760
accctgggca tccagctgag cccctacaac ctgagcacac tggaggatct gaacacccgg 2820
tggaaactgc tgcaggtggc cgtggaggat agagtgaggc agctgcacga agcccacaga 2880
gacttcggcc ctgcctccca gcacttcctg agcaccagcg tgcagggccc ctgggagaga 2940
gccatctccc ccaacaaagt gccctactac atcaaccacg agacccagac cacctgctgg 3000
gaccacccta agatgaccga gctgtatcag agcctggccg acctgaacaa tgtgcggttc 3060
agcgcctaca gaaccgccat gaagctgcgg agactgcaga aggccctgtg cctggatctg 3120
ctgagcctga gcgccgcctg cgacgccctg gaccagcaca acctgaagca gaatgaccag 3180
cccatggaca tcctgcagat catcaactgc ctgaccacaa tctacgaccg gctggaacag 3240
gagcacaaca acctggtgaa tgtgcccctg tgcgtggaca tgtgcctgaa ttggctgctg 3300
aacgtgtacg acaccggcag gaccggcaga atccgcgtgc tgagcttcaa gaccggcatc 3360
atcagcctgt gcaaggccca cctggaggat aagtaccgct acctgttcaa gcaggtggcc 3420
agcagcaccg gcttctgcga tcagaggaga ctgggcctgc tgctgcacga tagcatccag 3480
atccctaggc agctgggcga agtggccagc tttggcggca gcaacatcga gccctctgtg 3540
aggagctgct tccagttcgc caacaacaag cccgagatcg aggccgccct gttcctggac 3600
tggatgaggc tggagcctca gagcatggtg tggctgcctg tgctgcacag agtggccgcc 3660
gccgagaccg ccaagcacca ggccaagtgc aatatctgca aggagtgccc catcatcggc 3720
ttccggtaca ggagcctgaa gcacttcaac tacgacatct gccagagctg ctttttcagc 3780
ggcagagtgg ccaagggcca caaaatgcac taccccatgg tggagtactg cacccccacc 3840
acctccggcg aggatgtgag agacttcgcc aaagtgctga agaataagtt ccggaccaag 3900
cggtactttg ccaagcaccc caggatgggc tacctgcccg tgcagaccgt gctggaaggc 3960
gacaacatgg agacctga 3978
<210> 12
<211> 8912
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> hCK-B84表达盒的核苷酸序列
<400> 12
aattcccatc atcaataata taccttattt tggattgaag ccaatatgat aatgaggggg 60
tggagtttgt gacgtggcgc ggggcgtggg aacggggcgg gtgacgtagt agtctctaga 120
ggtccccagc gaccttgacg ggcatctgcc cggcatttct gacagctttg tgaactgggt 180
ggccgagaag gaatgggagt tgccgccaga ttctgacatg gatctgaatc tgattgagca 240
ggcacccctg accgtggccg agaagctgca tcgctggcgt aatagcgaag aggcccgcac 300
cgatcgccct tcccaacagt tgcgcagcct gaatggcgaa tggaattcca gacgattgag 360
cgtcaaaatg taggtatttc catgagcgtt tttcctgttg caatggctgg cggtaatatt 420
gttctggata ttaccagcaa ggccgatagt ttgagttctt ctactcaggc aagtgatgtt 480
attactaatc aaagaagtat tgcgacaacg gttaatttgc gtgatggaca gactctttta 540
ctcggtggcc tcactgatta taaaaacact tctcaggatt ctggcgtacc gttcctgtct 600
aaaatccctt taatcggcct cctgtttagc tcccgctctg attctaacga ggaaagcacg 660
ttatacgtgc tcgtcaaagc aaccatagta cgcgccctgt agcggcgcat taagcgcggc 720
gggtgtggtg gttacgcgca gcgtgaccgc tacacttgcc agcgccctag cgcccgctcc 780
tttcgctttc ttcccttcct ttctcgccac gttcgccggc tttccccgtc aagctctaaa 840
tcgggggctc cctttagggt tccgatttag tgctttacgg cacctcgacc ccaaaaaact 900
tgattagggt gatggttcac gtagtgggcc atcgccctga tagacggttt ttcgcccttt 960
gacgttggag tccacgttct ttaatagtgg actcttgttc caaactggaa caacactcaa 1020
ccctatctcg gtctattctt ttgatttata agggattttg ccgatttcgg cctattggtt 1080
aaaaaatgag ctgatttaac aaaaatttaa cgcgaatttt aacaaaatat taacgtttac 1140
aatttaaata tttgcttata caatcttcct gtttttgggg cttttctgat tatcaaccgg 1200
ggtacatatg attgacatgc tagttttacg attaccgttc atcgcctgca gggggggggg 1260
ggggggggtt ggccactccc tctctgcgcg ctcgctcgct cactgaggcc gggcgaccaa 1320
aggtcgcccg acgcccgggc tttgcccggg cggcctcagt gagcgagcga gcgcgcagag 1380
agggagtggc caactccatc actaggggtt cctagatctg aattcggtac cccactacgg 1440
gtttaggctg cccatgtaag gaggcaaggc ctggggacac ccgagatgcc tggttataat 1500
taacccagac atgtggctgc cccccccccc cccaacacct gctgcctcta aaaataaccc 1560
tgtccctggt ggatcccctg catgcgaaga tcttcgaaca aggctgtggg ggactgaggg 1620
caggctgtaa caggcttggg ggccagggct tatacgtgcc tgggactccc aaagtattac 1680
tgttccatgt tcccggcgaa gggccagctg tcccccgcca gctagactca gcacttagtt 1740
taggaaccag tgagcaagtc agcccttggg gcagcccata caaggccatg gggctgggca 1800
agctgcacgc ctgggtccgg ggtgggcacg gtgcccgggc aacgagctga aagctcatct 1860
gctctcaggg gcccctccct ggggacagcc cctcctggct agtcacaccc tgtaggctcc 1920
tctatataac ccaggggcac aggggctgcc ctcattctac caccacctcc acagcacaga 1980
cagacactca ggagccagcc agcgtcgagc ggccgatccg ccaccatgct ttggtgggag 2040
gaagtggagg actgctacga gagagaggac gtgcagaaga aaaccttcac caagtgggtg 2100
aacgcccagt tcagcaagtt cggcaagcag cacatcgaga acctgttcag cgacctgcag 2160
gatggcagga gactgctgga cctgctggag ggcctgaccg gccagaagct gcccaaggag 2220
aagggcagca ccagagtgca cgccctgaac aacgtgaaca aggccctgag agtgctgcag 2280
aacaacaacg tggacctggt gaacatcggc agcaccgaca tcgtggacgg caaccacaag 2340
ctgaccctgg gcctgatctg gaacatcatc ctgcactggc aggtgaagaa cgtgatgaag 2400
aacatcatgg ccggcctgca gcagaccaac agcgagaaga tcctgctgag ctgggtgagg 2460
cagagcacca gaaactaccc ccaggtgaac gtgatcaact tcaccacctc ctggagcgac 2520
ggcctggccc tgaacgccct gatccacagc cacagacccg acctgttcga ctggaacagc 2580
gtggtgtgtc agcagagcgc cacccagaga ctggagcacg ccttcaacat cgccagatac 2640
cagctgggca tcgagaagct gctggacccc gaggacgtgg acaccaccta ccccgacaag 2700
aaaagcatcc tcatgtacat taccagcctg ttccaggtgc tgccccagca ggtgtccatc 2760
gaggccatcc aggaagtgga aatgctgccc aggcccccca aagtgaccaa ggaggagcac 2820
ttccagctgc accaccagat gcactacagc cagcagatca cagtgagcct ggcccagggc 2880
tatgagagaa ccagcagccc caagcccaga ttcaagagct acgcctacac ccaggccgcc 2940
tacgtgacca cctccgaccc caccagaagc cccttcccca gccagcacct ggaggccccc 3000
gaggacaaga gcttcggcag cagcctgatg gagagcgaag tgaacctgga cagataccag 3060
accgccctgg aggaagtgct gtcctggctg ctgagcgccg aggacaccct gcaggcccag 3120
ggcgagatca gcaacgacgt ggaagtggtg aaggaccagt tccacaccca cgagggctac 3180
atgatggatc tgaccgccca ccagggcaga gtgggcaata tcctgcagct gggcagcaag 3240
ctgatcggca ccggcaagct gagcgaggac gaggagaccg aagtgcagga gcagatgaac 3300
ctgctgaaca gcagatggga gtgcctgaga gtggccagca tggagaagca gagcaacctg 3360
cacagagtgc tgatggacct gcagaaccag aagctgaagg agctgaacga ctggctgacc 3420
aagaccgagg agcggaccag aaagatggag gaggagcccc tgggccccga cctggaggac 3480
ctgaagagac aggtgcagca gcacaaagtg ctgcaggagg acctggagca ggagcaggtg 3540
cgcgtgaaca gcctgaccca catggtggtg gtcgtggacg agagcagcgg cgaccacgcc 3600
acagccgccc tggaagagca gctgaaagtg ctgggcgaca gatgggccaa tatttgtagg 3660
tggaccgagg acagatgggt gctgctgcag gaccagcccg acctggcccc tggcctgacc 3720
accatcggcg ccagccccac ccagaccgtg accctggtga cccagcccgt ggtgacaaag 3780
gagaccgcca tcagcaagct ggagatgccc agctccctga tgctggaagt gcccacccac 3840
cgcctgctcc agcagttccc cctggacctg gagaagttcc tggcctggct gaccgaggcc 3900
gaaaccaccg ccaatgtgct ccaggacgcc actagaaagg agaggctgct ggaggacagc 3960
aagggcgtga aagagctgat gaagcagtgg caggatctgc agggcgaaat cgaggcccac 4020
accgacgtgt accacaacct ggacgagaac agccagaaga ttctgaggag cctggagggc 4080
agcgacgacg ccgtcctgct ccagaggagg ctggacaaca tgaacttcaa gtggagcgag 4140
ctgcggaaga agagcctgaa catccggagc cacctggaag ccagcagcga ccagtggaag 4200
agactgcacc tgagcctgca ggagctgctg gtgtggctgc agctgaagga cgacgagctg 4260
agcagacagg cccccatcgg cggcgacttc cccgccgtgc agaagcagaa cgacgtgcac 4320
cgggccttca agagggagct gaaaaccaag gaacccgtga tcatgagcac cctggagaca 4380
gtgcggatct tcctgaccga gcagcccctg gagggactgg agaagctgta ccaggagccc 4440
agagagctgc cccccgagga gagagcccag aacgtgacca ggctgctgag aaagcaggcc 4500
gaggaagtga ataccgagtg ggagaagctg aatctgcaca gcgccgactg gcagagaaag 4560
atcgacgaga ccctggagag actccaggaa ctgcaggaag ccaccgacga gctggacctg 4620
aagctgagac aggccgaagt gatcaagggc agctggcagc ctgtgggcga tctgctgatc 4680
gactccctgc aggatcacct ggagaaagtg aaggccctgc ggggcgagat cgcccccctg 4740
aaggagaatg tgagccacgt gaacgacctg gccagacagc tgaccaccct gggcatccag 4800
ctgagcccct acaacctgag cacactggag gatctgaaca cccggtggaa actgctgcag 4860
gtggccgtgg aggatagagt gaggcagctg cacgaagccc acagagactt cggccctgcc 4920
tcccagcact tcctgagcac cagcgtgcag ggcccctggg agagagccat ctcccccaac 4980
aaagtgccct actacatcaa ccacgagacc cagaccacct gctgggacca ccctaagatg 5040
accgagctgt atcagagcct ggccgacctg aacaatgtgc ggttcagcgc ctacagaacc 5100
gccatgaagc tgcggagact gcagaaggcc ctgtgcctgg atctgctgag cctgagcgcc 5160
gcctgcgacg ccctggacca gcacaacctg aagcagaatg accagcccat ggacatcctg 5220
cagatcatca actgcctgac cacaatctac gaccggctgg aacaggagca caacaacctg 5280
gtgaatgtgc ccctgtgcgt ggacatgtgc ctgaattggc tgctgaacgt gtacgacacc 5340
ggcaggaccg gcagaatccg cgtgctgagc ttcaagaccg gcatcatcag cctgtgcaag 5400
gcccacctgg aggataagta ccgctacctg ttcaagcagg tggccagcag caccggcttc 5460
tgcgatcaga ggagactggg cctgctgctg cacgatagca tccagatccc taggcagctg 5520
ggcgaagtgg ccagctttgg cggcagcaac atcgagccct ctgtgaggag ctgcttccag 5580
ttcgccaaca acaagcccga gatcgaggcc gccctgttcc tggactggat gaggctggag 5640
cctcagagca tggtgtggct gcctgtgctg cacagagtgg ccgccgccga gaccgccaag 5700
caccaggcca agtgcaatat ctgcaaggag tgccccatca tcggcttccg gtacaggagc 5760
ctgaagcact tcaactacga catctgccag agctgctttt tcagcggcag agtggccaag 5820
ggccacaaaa tgcactaccc catggtggag tactgcaccc ccaccacctc cggcgaggat 5880
gtgagagact tcgccaaagt gctgaagaat aagttccgga ccaagcggta ctttgccaag 5940
caccccagga tgggctacct gcccgtgcag accgtgctgg aaggcgacaa catggagacc 6000
tgatgaggag ctcgagaggc ctaataaaga gctcagatgc atcgatcaga gtgtgttggt 6060
tttttgtgtg agatctagga acccctagtg atggagttgg ccactccctc tctgcgcgct 6120
cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt tggtcgcccg 6180
gcctcagtga gcgagcgagc gcgcagagag ggagtggcca accccccccc ccccccccct 6240
gcaggcgatt ctcttgtttg ctccagactc tcaggcaatg acctgatagc ctttgtagag 6300
acctctcaaa aatagctacc ctctccggca tgaatttatc agctagaacg gttgaatatc 6360
atattgatgg tgatttgact gtctccggcc tttctcaccc gtttgaatct ttacctacac 6420
attactcagg cattgcattt aaaatatatg agggttctaa aaatttttat ccttgcgttg 6480
aaataaaggc ttctcccgca aaagtattac agggtcataa tgtttttggt acaaccgatt 6540
tagctttatg ctctgaggct ttattgctta attttgctaa ttctttgcct tgcctgtatg 6600
atttattgga tgttggaatt cctgatgcgg tattttctcc ttacgcatct gtgcggtatt 6660
tcacaccgca tatggtgcac tctcagtaca atctgctctg atgccgcata gttaagccag 6720
ccccgacacc cgccaacacc cgctgacgcg ccctgacggg cttgtctgct cccggcatcc 6780
gcttacagac aagctgtgac cgtctccggg agctgcatgt gtcagaggtt ttcaccgtca 6840
tcaccgaaac gcgcgagacg aaagggcctc gtgatacgcc tatttttata ggttaatgtc 6900
atgataataa tggtttctta gacgtcaggt ggcacttttc ggggaaatgt gcgcggaacc 6960
cctatttgtt tatttttcta aatacattca aatatgtatc cgctcatgag acaataaccc 7020
tgataaatgc ttcaataata ttgaaaaagg aagagtatga gtattcaaca tttccgtgtc 7080
gcccttattc ccttttttgc ggcattttgc cttcctgttt ttgctcaccc agaaacgctg 7140
gtgaaagtaa aagatgctga agatcagttg ggtgcacgag tgggttacat cgaactggat 7200
ctcaacagcg gtaagatcct tgagagtttt cgccccgaag aacgttttcc aatgatgagc 7260
acttttaaag ttctgctatg tggcgcggta ttatcccgta ttgacgccgg gcaagagcaa 7320
ctcggtcgcc gcatacacta ttctcagaat gacttggttg agtactcacc agtcacagaa 7380
aagcatctta cggatggcat gacagtaaga gaattatgca gtgctgccat aaccatgagt 7440
gataacactg cggccaactt acttctgaca acgatcggag gaccgaagga gctaaccgct 7500
tttttgcaca acatggggga tcatgtaact cgccttgatc gttgggaacc ggagctgaat 7560
gaagccatac caaacgacga gcgtgacacc acgatgcctg tagcaatggc aacaacgttg 7620
cgcaaactat taactggcga actacttact ctagcttccc ggcaacaatt aatagactgg 7680
atggaggcgg ataaagttgc aggaccactt ctgcgctcgg cccttccggc tggctggttt 7740
attgctgata aatctggagc cggtgagcgt gggtctcgcg gtatcattgc agcactgggg 7800
ccagatggta agccctcccg tatcgtagtt atctacacga cggggagtca ggcaactatg 7860
gatgaacgaa atagacagat cgctgagata ggtgcctcac tgattaagca ttggtaactg 7920
tcagaccaag tttactcata tatactttag attgatttaa aacttcattt ttaatttaaa 7980
aggatctagg tgaagatcct ttttgataat ctcatgacca aaatccctta acgtgagttt 8040
tcgttccact gagcgtcaga ccccgtagaa aagatcaaag gatcttcttg agatcctttt 8100
tttctgcgcg taatctgctg cttgcaaaca aaaaaaccac cgctaccagc ggtggtttgt 8160
ttgccggatc aagagctacc aactcttttt ccgaaggtaa ctggcttcag cagagcgcag 8220
ataccaaata ctgtccttct agtgtagccg tagttaggcc accacttcaa gaactctgta 8280
gcaccgccta catacctcgc tctgctaatc ctgttaccag tggctgctgc cagtggcgat 8340
aagtcgtgtc ttaccgggtt ggactcaaga cgatagttac cggataaggc gcagcggtcg 8400
ggctgaacgg ggggttcgtg cacacagccc agcttggagc gaacgaccta caccgaactg 8460
agatacctac agcgtgagct atgagaaagc gccacgcttc ccgaagggag aaaggcggac 8520
aggtatccgg taagcggcag ggtcggaaca ggagagcgca cgagggagct tccaggggga 8580
aacgcctggt atctttatag tcctgtcggg tttcgccacc tctgacttga gcgtcgattt 8640
ttgtgatgct cgtcaggggg gcggagccta tggaaaaacg ccagcaacgc ggccttttta 8700
cggttcctgg ccttttgctg gccttttgct cacatgttct ttcctgcgtt atcccctgat 8760
tctgtggata accgtattac cgcctttgag tgagctgata ccgctcgccg cagccgaacg 8820
accgagcgca gcgagtcagt gagcgaggaa gcggaagagc gcccaatacg caaaccgcct 8880
ctccccgcgc gttggccgat tcattaatgc ag 8912
<210> 13
<211> 1325
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> hCK-B84表达盒的蛋白产物的氨基酸序列
<400> 13
Met Leu Trp Trp Glu Glu Val Glu Asp Cys Tyr Glu Arg Glu Asp Val
1 5 10 15
Gln Lys Lys Thr Phe Thr Lys Trp Val Asn Ala Gln Phe Ser Lys Phe
20 25 30
Gly Lys Gln His Ile Glu Asn Leu Phe Ser Asp Leu Gln Asp Gly Arg
35 40 45
Arg Leu Leu Asp Leu Leu Glu Gly Leu Thr Gly Gln Lys Leu Pro Lys
50 55 60
Glu Lys Gly Ser Thr Arg Val His Ala Leu Asn Asn Val Asn Lys Ala
65 70 75 80
Leu Arg Val Leu Gln Asn Asn Asn Val Asp Leu Val Asn Ile Gly Ser
85 90 95
Thr Asp Ile Val Asp Gly Asn His Lys Leu Thr Leu Gly Leu Ile Trp
100 105 110
Asn Ile Ile Leu His Trp Gln Val Lys Asn Val Met Lys Asn Ile Met
115 120 125
Ala Gly Leu Gln Gln Thr Asn Ser Glu Lys Ile Leu Leu Ser Trp Val
130 135 140
Arg Gln Ser Thr Arg Asn Tyr Pro Gln Val Asn Val Ile Asn Phe Thr
145 150 155 160
Thr Ser Trp Ser Asp Gly Leu Ala Leu Asn Ala Leu Ile His Ser His
165 170 175
Arg Pro Asp Leu Phe Asp Trp Asn Ser Val Val Cys Gln Gln Ser Ala
180 185 190
Thr Gln Arg Leu Glu His Ala Phe Asn Ile Ala Arg Tyr Gln Leu Gly
195 200 205
Ile Glu Lys Leu Leu Asp Pro Glu Asp Val Asp Thr Thr Tyr Pro Asp
210 215 220
Lys Lys Ser Ile Leu Met Tyr Ile Thr Ser Leu Phe Gln Val Leu Pro
225 230 235 240
Gln Gln Val Ser Ile Glu Ala Ile Gln Glu Val Glu Met Leu Pro Arg
245 250 255
Pro Pro Lys Val Thr Lys Glu Glu His Phe Gln Leu His His Gln Met
260 265 270
His Tyr Ser Gln Gln Ile Thr Val Ser Leu Ala Gln Gly Tyr Glu Arg
275 280 285
Thr Ser Ser Pro Lys Pro Arg Phe Lys Ser Tyr Ala Tyr Thr Gln Ala
290 295 300
Ala Tyr Val Thr Thr Ser Asp Pro Thr Arg Ser Pro Phe Pro Ser Gln
305 310 315 320
His Leu Glu Ala Pro Glu Asp Lys Ser Phe Gly Ser Ser Leu Met Glu
325 330 335
Ser Glu Val Asn Leu Asp Arg Tyr Gln Thr Ala Leu Glu Glu Val Leu
340 345 350
Ser Trp Leu Leu Ser Ala Glu Asp Thr Leu Gln Ala Gln Gly Glu Ile
355 360 365
Ser Asn Asp Val Glu Val Val Lys Asp Gln Phe His Thr His Glu Gly
370 375 380
Tyr Met Met Asp Leu Thr Ala His Gln Gly Arg Val Gly Asn Ile Leu
385 390 395 400
Gln Leu Gly Ser Lys Leu Ile Gly Thr Gly Lys Leu Ser Glu Asp Glu
405 410 415
Glu Thr Glu Val Gln Glu Gln Met Asn Leu Leu Asn Ser Arg Trp Glu
420 425 430
Cys Leu Arg Val Ala Ser Met Glu Lys Gln Ser Asn Leu His Arg Val
435 440 445
Leu Met Asp Leu Gln Asn Gln Lys Leu Lys Glu Leu Asn Asp Trp Leu
450 455 460
Thr Lys Thr Glu Glu Arg Thr Arg Lys Met Glu Glu Glu Pro Leu Gly
465 470 475 480
Pro Asp Leu Glu Asp Leu Lys Arg Gln Val Gln Gln His Lys Val Leu
485 490 495
Gln Glu Asp Leu Glu Gln Glu Gln Val Arg Val Asn Ser Leu Thr His
500 505 510
Met Val Val Val Val Asp Glu Ser Ser Gly Asp His Ala Thr Ala Ala
515 520 525
Leu Glu Glu Gln Leu Lys Val Leu Gly Asp Arg Trp Ala Asn Ile Cys
530 535 540
Arg Trp Thr Glu Asp Arg Trp Val Leu Leu Gln Asp Gln Pro Asp Leu
545 550 555 560
Ala Pro Gly Leu Thr Thr Ile Gly Ala Ser Pro Thr Gln Thr Val Thr
565 570 575
Leu Val Thr Gln Pro Val Val Thr Lys Glu Thr Ala Ile Ser Lys Leu
580 585 590
Glu Met Pro Ser Ser Leu Met Leu Glu Val Pro Thr His Arg Leu Leu
595 600 605
Gln Gln Phe Pro Leu Asp Leu Glu Lys Phe Leu Ala Trp Leu Thr Glu
610 615 620
Ala Glu Thr Thr Ala Asn Val Leu Gln Asp Ala Thr Arg Lys Glu Arg
625 630 635 640
Leu Leu Glu Asp Ser Lys Gly Val Lys Glu Leu Met Lys Gln Trp Gln
645 650 655
Asp Leu Gln Gly Glu Ile Glu Ala His Thr Asp Val Tyr His Asn Leu
660 665 670
Asp Glu Asn Ser Gln Lys Ile Leu Arg Ser Leu Glu Gly Ser Asp Asp
675 680 685
Ala Val Leu Leu Gln Arg Arg Leu Asp Asn Met Asn Phe Lys Trp Ser
690 695 700
Glu Leu Arg Lys Lys Ser Leu Asn Ile Arg Ser His Leu Glu Ala Ser
705 710 715 720
Ser Asp Gln Trp Lys Arg Leu His Leu Ser Leu Gln Glu Leu Leu Val
725 730 735
Trp Leu Gln Leu Lys Asp Asp Glu Leu Ser Arg Gln Ala Pro Ile Gly
740 745 750
Gly Asp Phe Pro Ala Val Gln Lys Gln Asn Asp Val His Arg Ala Phe
755 760 765
Lys Arg Glu Leu Lys Thr Lys Glu Pro Val Ile Met Ser Thr Leu Glu
770 775 780
Thr Val Arg Ile Phe Leu Thr Glu Gln Pro Leu Glu Gly Leu Glu Lys
785 790 795 800
Leu Tyr Gln Glu Pro Arg Glu Leu Pro Pro Glu Glu Arg Ala Gln Asn
805 810 815
Val Thr Arg Leu Leu Arg Lys Gln Ala Glu Glu Val Asn Thr Glu Trp
820 825 830
Glu Lys Leu Asn Leu His Ser Ala Asp Trp Gln Arg Lys Ile Asp Glu
835 840 845
Thr Leu Glu Arg Leu Gln Glu Leu Gln Glu Ala Thr Asp Glu Leu Asp
850 855 860
Leu Lys Leu Arg Gln Ala Glu Val Ile Lys Gly Ser Trp Gln Pro Val
865 870 875 880
Gly Asp Leu Leu Ile Asp Ser Leu Gln Asp His Leu Glu Lys Val Lys
885 890 895
Ala Leu Arg Gly Glu Ile Ala Pro Leu Lys Glu Asn Val Ser His Val
900 905 910
Asn Asp Leu Ala Arg Gln Leu Thr Thr Leu Gly Ile Gln Leu Ser Pro
915 920 925
Tyr Asn Leu Ser Thr Leu Glu Asp Leu Asn Thr Arg Trp Lys Leu Leu
930 935 940
Gln Val Ala Val Glu Asp Arg Val Arg Gln Leu His Glu Ala His Arg
945 950 955 960
Asp Phe Gly Pro Ala Ser Gln His Phe Leu Ser Thr Ser Val Gln Gly
965 970 975
Pro Trp Glu Arg Ala Ile Ser Pro Asn Lys Val Pro Tyr Tyr Ile Asn
980 985 990
His Glu Thr Gln Thr Thr Cys Trp Asp His Pro Lys Met Thr Glu Leu
995 1000 1005
Tyr Gln Ser Leu Ala Asp Leu Asn Asn Val Arg Phe Ser Ala Tyr
1010 1015 1020
Arg Thr Ala Met Lys Leu Arg Arg Leu Gln Lys Ala Leu Cys Leu
1025 1030 1035
Asp Leu Leu Ser Leu Ser Ala Ala Cys Asp Ala Leu Asp Gln His
1040 1045 1050
Asn Leu Lys Gln Asn Asp Gln Pro Met Asp Ile Leu Gln Ile Ile
1055 1060 1065
Asn Cys Leu Thr Thr Ile Tyr Asp Arg Leu Glu Gln Glu His Asn
1070 1075 1080
Asn Leu Val Asn Val Pro Leu Cys Val Asp Met Cys Leu Asn Trp
1085 1090 1095
Leu Leu Asn Val Tyr Asp Thr Gly Arg Thr Gly Arg Ile Arg Val
1100 1105 1110
Leu Ser Phe Lys Thr Gly Ile Ile Ser Leu Cys Lys Ala His Leu
1115 1120 1125
Glu Asp Lys Tyr Arg Tyr Leu Phe Lys Gln Val Ala Ser Ser Thr
1130 1135 1140
Gly Phe Cys Asp Gln Arg Arg Leu Gly Leu Leu Leu His Asp Ser
1145 1150 1155
Ile Gln Ile Pro Arg Gln Leu Gly Glu Val Ala Ser Phe Gly Gly
1160 1165 1170
Ser Asn Ile Glu Pro Ser Val Arg Ser Cys Phe Gln Phe Ala Asn
1175 1180 1185
Asn Lys Pro Glu Ile Glu Ala Ala Leu Phe Leu Asp Trp Met Arg
1190 1195 1200
Leu Glu Pro Gln Ser Met Val Trp Leu Pro Val Leu His Arg Val
1205 1210 1215
Ala Ala Ala Glu Thr Ala Lys His Gln Ala Lys Cys Asn Ile Cys
1220 1225 1230
Lys Glu Cys Pro Ile Ile Gly Phe Arg Tyr Arg Ser Leu Lys His
1235 1240 1245
Phe Asn Tyr Asp Ile Cys Gln Ser Cys Phe Phe Ser Gly Arg Val
1250 1255 1260
Ala Lys Gly His Lys Met His Tyr Pro Met Val Glu Tyr Cys Thr
1265 1270 1275
Pro Thr Thr Ser Gly Glu Asp Val Arg Asp Phe Ala Lys Val Leu
1280 1285 1290
Lys Asn Lys Phe Arg Thr Lys Arg Tyr Phe Ala Lys His Pro Arg
1295 1300 1305
Met Gly Tyr Leu Pro Val Gln Thr Val Leu Glu Gly Asp Asn Met
1310 1315 1320
Glu Thr
1325
Claims (17)
1.重组杂合蛋白,其包括:
全长人Utrophin的N端结构域、铰链H1、膜收缩蛋白样重复序列R1、膜收缩蛋白样重复序列R2、膜收缩蛋白样重复序列R3和铰链H2的前半部分,以及
全长人Dystrophin的膜收缩蛋白样重复序列R23、膜收缩蛋白样重复序列R24、铰链H4和CR结构域。
2.根据权利要求1所述的重组杂合蛋白,其中,所述重组杂合蛋白包含SEQ ID NO:4所示的氨基酸序列;优选地,所述重组杂合蛋白的氨基酸序列如SEQ ID NO:4所示。
3.编码权利要求1或2所述的重组杂合蛋白的核酸分子。
4.根据权利要求3所述的核酸分子,其核苷酸序列与SEQ ID NO:8或SEQ ID NO:10所示的核苷酸序列具有至少50%的同一性,优选具有至少50%、60%、70%、80%、85%、90%、95%、99%或100%的同一性。
5.根据权利要求4所述的核酸分子,其中,所述核酸分子包含SEQ ID NO:8或SEQ IDNO:10所示的核苷酸序列,优选地,所述核酸分子的核苷酸序列如SEQ ID NO:8或SEQ IDNO:10所示。
6.转基因表达盒,其包括:启动子、权利要求3至5中任一项所述的核酸分子、minipolyA。
7.根据权利要求6所述的转基因表达盒,其中,所述启动子选自:CB启动子、CAG启动子、肌肉肌酸激酶MCK启动子、人肌酸激酶hCK启动子、截短的人肌酸激酶CK(shCK)启动子、骨骼肌α-actin启动子、心肌α-actin启动子、肌球蛋白重链(MyHC)启动子、肌球蛋白轻链2(MLC2)启动子、肌球蛋白轻链3F启动子、结蛋白(desmin)基因启动子和生肌调控因子家族(MyoG、Myf5、Mrf4和Myogenin)等肌肉特异性基因的启动子;优选地,所述启动子为hCK启动子或shCK启动子;更优选地,所述启动子为shCK启动子。
8.根据权利要求6或7所述的转基因表达盒,其中,所述启动子的核苷酸序列如SEQ IDNO:9所示。
9.根据权利要求6至8中任一项所述的转基因表达盒,其中,所述转基因表达盒还包括调控元件,例如位于两端的两个ITR,所述ITR为正常ITR或缩短ITR;优选地,所述两个ITR均为145bp的正常ITR。
10.根据权利要求6至9中任一项所述的转基因表达盒,其中,所述转基因表达盒还包括复制起点、聚腺苷酸化信号、内部核糖体进入位点(IRES)和/或2A信号,例如P2A、T2A和F2A。
11.根据权利要求6至10中任一项所述的转基因表达盒,其中,所述转基因表达盒的核苷酸序列如SEQ ID NO:3、SEQ ID NO:5、SEQ ID NO:6或SEQ ID NO:7所示。
12.基因递送***,其包括:权利要求6至11中任一项所述的转基因表达盒和AAV衣壳蛋白。
13.根据权利要求12所述的基因递送***,其中,所述AAV衣壳蛋白为天然AAV衣壳蛋白或人工改造的AAV衣壳蛋白;优选地,所述AAV选自:AAV1、AAV2、AAV3、AAV4、AAV5、AAV6、AAV7、AAV8、AAV9、AAV10、AAV11,AAV12、AAV-DJ、AAV-DJ8、AAV-DJ9、AAVrh8、AAVrh8R、AAVrh10、AAVrh39、AAVrh43、AAV32.33、AAV3B、AAVv66、AAVXL32和AAV.PHP.B。
14.权利要求6至11中任一项所述的转基因表达盒或权利要求12或13所述的基因递送***在制备用于治疗肌营养不良症的药物中的应用。
15.根据权利要求14所述的应用,其中,所述肌营养不良症包括:杜氏型肌营养不良症、贝克型肌营养不良症,以及其他肌肉退行性疾病;优选地,所述肌营养不良症为杜氏型肌营养不良症。
16.药物,其包含:权利要求1或2所述的重组杂合蛋白、权利要求3至5中任一项所述的核酸分子、权利要求6至11中任一项所述的转基因表达盒和权利要求12或13所述的基因递送***中的一种,以及赋形剂。
17.根据权利要求16所述的药物,其中,所述药物通过全身途径或局部途径施用,例如静脉内施用、肌内施用、皮下施用、经口施用、局部接触、腹膜内施用和病灶内施用;优选地,所述药物通过全身途径施用,例如静脉内施用;还优选地,所述药物通过局部途径施用于肌肉,例如注射至肱二头肌或腓肠肌。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109641944A (zh) * | 2016-06-21 | 2019-04-16 | 班布疗法公司 | 优化的小型抗肌萎缩蛋白基因和表达盒和它们的用途 |
CN111683673A (zh) * | 2017-12-05 | 2020-09-18 | 皇家霍洛威和贝德福德新学院 | 肌营养不良症的治疗 |
Family Cites Families (10)
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WO2001083695A2 (en) * | 2000-04-28 | 2001-11-08 | Xiao Xiao | Dna sequences encoding dystrophin minigenes and methods of use thereof |
EP3194600B1 (en) * | 2014-07-26 | 2019-08-28 | Consiglio Nazionale Delle Ricerche | Compositions and methods for treatment of muscular dystrophy |
IL286316B2 (en) * | 2015-01-16 | 2023-03-01 | Univ Washington | New micro-dystrophins and related method of use |
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CN111057157A (zh) * | 2020-01-02 | 2020-04-24 | 北京辉润合众生物科技有限公司 | 一种抗肌萎缩融合蛋白mDp116 |
RU2767335C1 (ru) * | 2021-03-02 | 2022-03-17 | Общество с ограниченной ответственностью «Марлин Биотех» | Химерные белки на основе утрофина и дистрофина человека и их применение для лечения миодистрофии Дюшенна |
CN114316070B (zh) * | 2021-12-29 | 2022-11-15 | 上海勉亦生物科技有限公司 | 用于治疗肌营养不良症的转基因表达盒 |
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109641944A (zh) * | 2016-06-21 | 2019-04-16 | 班布疗法公司 | 优化的小型抗肌萎缩蛋白基因和表达盒和它们的用途 |
CN111683673A (zh) * | 2017-12-05 | 2020-09-18 | 皇家霍洛威和贝德福德新学院 | 肌营养不良症的治疗 |
Non-Patent Citations (1)
Title |
---|
赵丹丹: "肌肉特异性基因启动子的上游转录调控元件研究进展", 《中国细胞生物学学报》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023124741A1 (zh) * | 2021-12-29 | 2023-07-06 | 上海勉亦生物科技有限公司 | 用于治疗肌营养不良症的转基因表达盒 |
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