CN113423434A

CN113423434A - 用于基因递送的重组腺相关病毒载体

Info

Publication number: CN113423434A
Application number: CN201980088032.2A
Authority: CN
Inventors: T.J.米勒; L.帕德吉马斯
Original assignee: Abe Onna Therapeutics Ltd
Current assignee: Abe Onna Therapeutics Ltd; Abeona Therapeutics Inc
Priority date: 2018-12-05
Filing date: 2019-12-04
Publication date: 2021-09-21
Also published as: BR112021009913A2; EP3890786A4; JP2022515338A; IL283546A; KR20220022107A; CA3121177A1; MX2021006646A; AU2019391042A1; US20220090129A1; EP3890786A1; WO2020117898A1

Abstract

本文提供了用于改进基因疗法的重组AAV载体、AAV病毒载体和衣壳蛋白，以及它们的制备和使用方法。

Description

用于基因递送的重组腺相关病毒载体

相关申请的交叉引用

本申请要求2018年12月5日提交的美国临时申请62/775,871；2019年2月5日提交的62/801,195；2019年6月18日提交的62/863,126和2019年10月14日提交的62/914,856的优先权，这些申请各自出于所有目的以引用方式整体并入本文中。

通过引用并入序列表

据此以电子文档提交的文本文件的内容全文以引用方式并入本文：序列表的计算机可读格式副本(文件名：ABEO_002_04WO_SeqList_ST25，创建日期：2019年12月3日；文件大小：556kb)。

背景技术

腺相关病毒载体是基因疗法的有前途的递送载体。然而，它们的治疗功效因载体的递送效率或有限的组织趋性而受到影响。因此，迫切需要具有更佳治疗潜力的新AAV载体。

发明内容

本公开整体涉及基因疗法领域，并且具体地涉及具有新衣壳蛋白的重组腺相关病毒(AAV)载体颗粒(也称为AAV病毒载体)、它们的制备、以及它们递送转基因以治疗或预防疾病或病症的用途。

附图说明

图1用于AIM衣壳文库构建的策略。

图2A：组织培养中转导效率的比较。将HEK 293细胞以50,000个细胞/孔接种于96孔板中。用含有AAV9-GFP或AAV214-GFP病毒的衣壳以5E+5的MOI转导细胞。在转导后45小时拍摄图像。

图2B给予AAV9或AAV214病毒的2E+11病毒基因组(vg)的小鼠的不同组织中的转导效率的比较。

图2C给予AAV9或AAV214病毒2E+11vg的小鼠的脑中的转导效率和表达水平的比较。

图3A AAV施用后小鼠视网膜的扫描激光检眼镜成像。通过视网膜下(右眼)和玻璃体内(左眼)注射，给野生型C57BL/6J小鼠施用经标记的AAV血清型。对于两种施用方法，注射1μL 5E+12vg/mL(5E+9vg/眼)的AAV载体，10天后用HRA2 Spectralis扫描激光检眼镜(Heidelberg Engineering,Carlsbad,CA)对动物成像。从图中省略了白内障妨碍充分观察的图像。

图3B对玻璃体内给予AAV204-GFP的小鼠眼的IHC分析。

图4比较了通过RT-qPCR得到的灵长类动物中由AAV204或AAV9转导所介导的GFP表达。虚线对应于计算为-RT平均值的背景加上2或4个标准偏差。

图5A-5F示出AAV204介导的眼表达。图5A示出由玻璃体内注射的AAV204介导的转导扩散，主要是外周和一些中央凹。图5B示出(通过GFP表达)在灵长类动物玻璃体内注射AAV204病毒后，包括感光细胞和RPE细胞在内的多种视网膜细胞的转导。图5C示出黄斑中大量的感光细胞和RPE转导，其中大多数视锥(负责色觉的感光细胞)是集中的。图5D-5F示出由VMD2(卵黄状黄斑变性-2启动子)驱动的AAV204的GFP的表达，VMD2是RPE的细胞特异性启动子。在玻璃体内注射2.5×10¹²个病毒基因组(vg)载体后的第14天(图5D)和第28天(图5E)进行SLO成像。图5F示出第28天时外周的GFP表达和核(DAPI)。

图6示出对离体进行的NHP眼外植体转导的IHC分析。

图7中和抗体定量策略。发光不存在指示靶AAV被中和抗体结合。

图8展示AAV204和AAV9的不同免疫原性。使用内部开发的方法获得中和抗体滴度。将AAV9-Luc或pA-AAV204-Luc与各种血清稀释液在25,000的MOI下温育。温育后，将病毒/血清混合物转移到含有20,000个Lec2细胞的孔中，并与细胞一起温育24小时，之后测量发光并与来自仅用相同MOI的病毒转导的细胞的对照值进行比较。

图9示出使用AAV204或AAV6(AAV肺转导的基准)通过气管内递送的肺转导的比较。

图10A-10C示出通过FLIPR测定得到的CFTRΔR和全长表达盒的功能性(图10A)和对AAV204包装的CFTRΔR表达盒处理的剂量反应(图10B)。图10C示出就通过FLIPR测定的膜电位而言，CFTRΔR与全长密码子优化的CFTR表达的比较。用表达这些蛋白的AAV204转导293细胞，监测荧光变化。读取基线1分钟，然后向细胞中加入50M毛喉素。

图11A-11C示出AAV204转导培养的CF患者细胞的能力(图11A)，细胞膜中CFTRΔR表达和正确定位(图11B)，并且CFTRΔR表达使人CF患者细胞中的CFTR电流恢复(图11C)。

图12A示出将包含CFTR转基因的AAV204颗粒经鼻施用给纤维化小鼠模型的体内效应。图12B示出AAV204/CFTRΔR治疗(通过增加鼻膜电位)在不同CF患者细胞中的效应。

图13示出在静脉内施用病毒颗粒30天后，AAV9-CLN3和AAV214-CLN3载体在CLN3Δex7/8小鼠模型中的生物分布。

图14示出通过RT-qPCR测量的AAV9-CLN3和AAV214-CLN3载体在CLN3Δex7/8小鼠脑组织中的表达。

图15示出GLA在转导的HEK293细胞中表达的免疫印迹。

图16示出AAV施用后C57BL/6小鼠的血浆、脑、肝、脊髓、心、肾和眼中GLA的酶活性(超生理)。

图17示出通过静脉注射进行AAV施用后C57BL/6小鼠的脑、二头肌、膈膜和肝中GAA的酶活性。

图18A-18B示出通过转染在HEK293细胞中表达的重组hGAA的免疫印迹(图18A)和酶促分析(图18B)。

图19A-19E示出AAV施用后C57BL/6小鼠的血浆(图19A)、脑(图19B)、二头肌(图19C)、膈膜(图19D)或肝(图19E)中GAA的酶活性。图19F示出用AAV衣壳经IV治疗的GAA-/-小鼠中的糖原水平。数据表示为GAA-/-小鼠中发现的糖原的百分比％。糖原减少表明通过AAV9和AAV214介导的密码子优化的GAA酶的表达使GAA功能恢复。

图20示出来自AAV204(SEQ ID NO:2)和AAV6(SEQ ID NO:63)的VP1氨基酸序列的比对。

图21示出来自下列的VP1蛋白氨基酸序列的比对：AAV214(SEQ ID NO:3)；AAV214A(SEQ ID NO:30)、AAV214AB(SEQ ID NO:84)、AAV214e(SEQ ID NO:31)、AAV214e8(SEQ IDNO:32)、AAV214e9(SEQ ID NO:33)、AAV214e10(SEQ ID NO:34)、ITB204_45(SEQ ID NO:49)、AAV9(SEQ ID NO:71)和AAV8(SEQ ID NO:67)。

图22示出来自下列的VP2蛋白氨基酸序列的比对：AAV214(SEQ ID NO:35)；AAV214A(SEQ ID NO:36)、AAV214AB(SEQ ID NO:85)、AAV214e(SEQ ID NO:37)、AAV214e8(SEQ ID NO:38)、AAV214e9(SEQ ID NO:39)、AAV214e10(SEQ ID NO:40)、ITB204_45(SEQID NO:50)、AAV9(SEQ ID NO:72)和AAV8(SEQ ID NO:68)。

图23示出来自下列的VP3蛋白氨基酸序列的比对：AAV214(SEQ ID NO:41)；AAV214A(SEQ ID NO:42)、AAV214AB(SEQ ID NO:86)、AAV214e(SEQ ID NO:43)、AAV214e8(SEQ ID NO:44)、AAV214e9(SEQ ID NO:45)、AAV214e10(SEQ ID NO:46)、ITB204_45(SEQID NO:51)、AAV9(SEQ ID NO:73)和AAV8(SEQ ID NO:69)。

图24A示出肌内施用后由AAV110载体颗粒和AAV9载体颗粒递送的GFP转基因的表达。上图以白光示出左腿和右腿，示出了整体组织结构。下图示出GFP荧光。

图24B提供了与AAV9相比，图24A中获得的AAV110颗粒(ITCord1.10)的荧光的定量分析。

图25A-25C示出肌内施用后，由AAV110颗粒(ITCord1.10)递送的转基因相对于AAV9的表达。数据显示肌肉中的AAV110表达特别高。

图26A示出肌内施用表达GFP的AAV110和AAV9颗粒后，用于检测GFP表达的肌肉组织的免疫组织化学。图示出由AAV9载体颗粒表达的GFP(左下图)、由AAV110颗粒表达的GFP(右下图)和对照肌肉(上图)。用抗GFP抗体对组织进行染色。

图26B.IM递送的AAV214比AAV9转导更大的肌肉区域。通过IM注射后10天的免疫组织化学来分析大鼠全肌(股二头肌)的GFP或mCherry表达。用GFP和mCherry pAb探测固定和冷冻切片。与AAV9相比，AAV214展示出显著更大的转导区域，其主要局限于与注射位点一致的肌肉的上部。

图27示出荧光素酶的生物发光图像，所述荧光素酶以转基因表达并暴露于荧光素。在AAV214施用后28天获得数据。

图28比较了在AAV214和AAV9中静脉内递送的SMN-1蛋白的肌肉表达。

图29示出由AAV214和AAV9的变体介导的心脏和二头肌中作为转基因的GFP的表达。y轴示出每微克基因组DNA的病毒拷贝数的log10值。

图30示出VP1、VP2和VP3衣壳蛋白的示意图。VP1和VP2特异性部分与VP3部分一起标出，该VP3部分与产生的VP3蛋白相同。示出AAV214 VP3的氨基酸序列(SEQ ID NO:41)并指示可变区I-IX。AAV214的完整VP1蛋白氨基酸序列以SEQ ID NO:3提供。

图31A-31C说明AAV214治疗的动物证实AAV9中和抗体的产生减少。图31A示出测定经IM给予AAV9或AAV214的动物的针对AAV9的中和抗体。通过测定动物血清抑制AAV9转导的能力进行分析。萤光素酶载体导入允许的细胞类型，Lec2。转导后三天，测定细胞的萤光素酶活性。每组由2或3只大鼠组成，用于对照，AAV9或AAV214。图31B和31C示出与AAV9和AAV204的交叉反应性。图31B示出AAV9测试后各种AAV中和抗体的产生。图31C示出AAV204测试后各种AAV中和抗体的产生。

具体实施方式

下文将更全面地描述根据本公开的一些实施方案。然而，本公开的各方面可以以不同的形式来体现，并且不应被解释为限于本文所阐述的实施方案。相反，提供这些实施方案是为了使本公开透彻和完整，并且将向本领域技术人员充分传达本发明的范围。在本文的描述中使用的术语仅是为了描述特定实施方案的目的，而不是旨在限制。

除非另有定义，否则本文所用的所有术语(包括技术和科学术语)具有与本发明所属领域的普通技术人员通常理解的相同含义。还应当理解，诸如在常用词典中定义的那些术语应当被解释为具有与它们在本申请和相关领域的上下文中的含义一致的含义，并且不应当以理想化或过于正式的意义来解释，除非在此明确地如此定义。

除非上下文另外指出，否则特别旨在本文所述的本发明的各种特征可以以任何组合使用。此外，本公开还预期在实施方案中，可以排除或省略本文阐述的任何特征或特征的组合。为了说明，如果说明书陈述复合物包含组分A、B和C，明确意欲可单独地或组合地忽略和不要求保护A、B或C中任一种，或它们的组合。

除非明确地另外指出，否则所有指定的一些实施方案、特征和术语旨在包括所叙述的实施方案、特征或术语以及它们的生物学等同物。

通过引用并入

本文引用的所有参考文献、文章、出版物、专利公布和专利申请出于所有目的以引用方式整体并入。然而，本文引用的任何参考文献、文章、出版物、专利公布和专利申请的提及不得且不应被视为承认或以任何形式表明它们构成有效的现有技术或形成世界上任何国家公知常识的一部分。

定义

除非另有说明，本技术的实施将采用有机化学、药理学、免疫学、分子生物学、微生物学、细胞生物学和重组DNA的常规技术，这些技术在本领域的技术范围内。参见，例如，Sambrook，Fritsch和Maniatis，Molecular Cloning：A Laboratory Manual，第2版(1989)；Current Protocols In Molecular Biology(F.M.Ausubel等编辑，(1987))；the seriesMethods in Enzymology(Academic Press,Inc.):PCR 2:A Practical Approach(M.J.MacPherson,B.D.Hames和G.R.Taylor编辑(1995))，Harlow和Lane编辑，(1988)Antibodies,a Laboratory Manual,and Animal Cell Culture(RI.Freshney，编(1987))。

如在本发明的说明书和所附权利要求中所使用的，单数形式“一/一个”、和“该/所述”也旨在包括复数形式，除非上下文另有明确指示。

如本文所用，术语“包括”旨在表示组合物和方法包括所述的要素，但不排除其他要素。如本文所用，过渡短语“基本上由......组成”(和语法上的变体)应被解释为包括所述的材料或步骤以及那些本质上不影响所述实施方案的基本和新颖特征的材料或步骤。因此，本文所用的术语“基本上由......组成”不应解释为等同于“包含......”“由......组成”应意指排除多于微量的其它成分要素以及用于施用本发明所公开的组合物的实质性方法步骤。由这些过渡术语中的每一个定义的方面在本公开的范围内。

所有的数字名称，例如pH、温度、时间、浓度和分子量，包括范围，都是近似值，其以1.0或0.1的增量适当地，或以+/-15％、10％、5％、2％的变化可选地改变(+)或(-)。应当理解，尽管不总是明确地说明，所有的数字名称前面都有术语“约”。还应理解，尽管不总是明确地说明，但本文所述的试剂仅是示例性的，并且其等同物是本领域已知的。当涉及可测量值如量或浓度等时，本文所用的术语“约”是指包括指定量的20％、10％、5％、1％、0.5％或甚至0.1％的变化。

本文所公开的术语“可接受的”、“有效的”或“足够的”当用于描述任何组分、范围、剂型等的选择时意指所述组分、范围、剂型等适用于所公开的目的。

此外，如本文所用，“和/或”是指并且包括相关联的所列项目中的一个或多个项目的任意和所有可能组合，以及当以二者择一(“或”)解释时，组合的缺乏。

除非特别说明，术语“宿主细胞”包括真核宿主细胞，包括例如真菌细胞、酵母细胞、高等植物细胞、昆虫细胞和哺乳动物细胞。真核宿主细胞的非限制性实例包括猿、牛、猪、鼠、大鼠、鸟、爬行动物和人，例如HEK293细胞和293T细胞。

如本文所用，术语“分离的”是指基本上不含其它物质的分子或生物制品或细胞物质。

如本文所用，术语“核酸序列”和“多核苷酸”可互换使用，指任何长度的核苷酸(核糖核苷酸或脱氧核糖核苷酸)的聚合形式。因此，该术语包括但不限于单链、双链或双链DNA或RNA、基因组DNA、cDNA、DNA-RNA杂交体或包含、由或基本上由嘌呤和嘧啶碱基或其他天然的、化学或生物化学修饰的、非天然的或衍生的核苷酸碱基组成的聚合物。

“基因”指含有至少一个能够编码特定多肽或蛋白质的开放阅读框(ORF)的多核苷酸。“基因产物”或可选地“基因表达产物”指当基因转录和翻译时产生的氨基酸序列(例如肽或多肽)。

如本文所用，“表达”是指多核苷酸被转录成mRNA的两步过程和/或转录的mRNA随后被翻译成肽、多肽或蛋白质的过程。如果多核苷酸来自基因组DNA，则表达可包括在真核细胞中剪接mRNA。

“在转录控制下”是本领域熟知的术语，表示多核苷酸序列(通常是DNA序列)的转录依赖于其与有助于转录起始或促进转录的元件的可操作地连接。“可操作地连接”是指多核苷酸以允许它们在细胞中发挥功能的方式排列。一方面，本发明提供了与下游序列可操作地连接的启动子。

当术语“编码”应用于多核苷酸时，是指如果在其天然状态下或当通过本领域技术人员熟知的方法操作时，其可以被转录以产生多肽和/或其片段的mRNA，则称其“编码”多肽的多核苷酸。反义链是这种核酸的互补物，并且可以从其推导出编码序列。

本文所用的术语“启动子”是指控制序列，其是多核苷酸序列的区，在该区编码序列如基因或转基因的转录的起始和速率受到控制。启动子可以是例如组成型的、诱导型的、阻遏型的或组织特异性的。启动子可以含有调节蛋白和分子如RNA聚合酶和转录因子可以结合的遗传元件。非限制性示例性启动子包括劳斯肉瘤病毒(RSV)LTR启动子(任选地与RSV增强子一起)、巨细胞病毒(CMV)启动子、SV40启动子、二氢叶酸还原酶启动子、β-肌动蛋白启动子、磷酸甘油激酶(PGK)启动子、U6启动子、H1启动子、遍在鸡β-肌动蛋白杂合(CBh)启动子、小核RNA(U1a或U1b)启动子、MeCP2启动子、MeP418启动子、MeP426启动子、最小MeCP2启动子、VMD2启动子、mRho启动子或EFI启动子。

本文提供的其它非限制性示例性启动子包括但不限于EFla、Ubc、人β-肌动蛋白、CAG、TRE、Ac5、多角体蛋白、CaMKIIa、Gal1、TEF1、GDS、ADH1、Ubi和α-1-抗胰蛋白酶(hAAT)。本领域已知，可以修饰这些启动子的核苷酸序列以提高或降低mRNA转录的效率。参见，例如Gao等(2018)Mol.Ther.:Nucleic Acids 12:135-145(修饰7SK、U6和H1启动子的TATA盒以消除RNA聚合酶III转录并刺激RNA聚合酶II依赖性mRNA转录)。合成来源的启动子可用于普遍存在的或组织特异性表达。此外，病毒来源的启动子，其中一些如上所述，可用于本文公开的方法中，例如CMV、HIV、腺病毒和AAV启动子。在实施方案中，启动子与增强子一起使用以增加转录效率。增强子的非限制性实例包括间隙类视黄醇结合蛋白(IRBP)增强子、RSV增强子或CMV增强子。

增强子是增加靶序列表达的调节元件。“启动子/增强子”是含有能够提供启动子和增强子功能的序列的多核苷酸。例如，逆转录病毒的长末端重复同时含有启动子和增强子功能。增强子/启动子可以是“内源的”或“外源的”或“异源的”“内源”增强子/启动子是与基因组中的给定基因天然连接的增强子/启动子。“外源”或“异源”增强子/启动子是通过遗传操作(即分子生物学技术)与基因并置的增强子/启动子，使得该基因的转录由连接的增强子/启动子指导。用于本文提供的方法、组合物和构建体的连接的增强子/启动子的非限制性实例包括PDE启动子加IRBP增强子或CMV增强子加U1a启动子。本领域理解增强子可以远距离操作，而与它们相对于内源或异源启动子位置的方向无关。因此，进一步理解的是，在距启动子一定距离处操作的增强子因此“可操作地连接”到该启动子，而不管其在载体中的位置或其相对于启动子位置的取向。

术语“蛋白质”、“肽”和“多肽”可互换使用，并且在其最广泛的意义上是指两个或更多个氨基酸亚基、氨基酸类似物或肽模拟物的化合物。亚基可以通过肽键连接。在另一个方面，亚基可以通过其它键例如酯、醚等连接。蛋白质或肽必须含有至少两个氨基酸，并且对可以包含、由或基本上由蛋白质或肽序列组成的氨基酸的最大数目没有限制。本文所用术语“氨基酸”是指天然和/或非天然或合成的氨基酸，包括甘氨酸和D和L光学异构体、氨基酸类似物和肽模拟物。

如本文所用，术语“信号肽”或“信号多肽”意指通常存在于新合成的分泌或膜多肽或蛋白质的N末端的氨基酸序列。它用于将多肽导向特定的细胞位置，例如穿过细胞膜、进入细胞膜或进入细胞核。在实施方案中，信号肽在定位后被去除。信号肽的实例是本领域公知的。非限制性实例是描述于美国专利8,853,381、5,958,736和8,795,965中的那些。在实施方案中，信号肽可以是IDUA信号肽。

当涉及特定分子、生物材料或细胞物质时，术语“等同物”或“生物等同物”可互换使用，并且是指具有最小同源性同时仍保持所需结构或功能的那些。等同多肽的非限制性实例包括与参照多肽(例如野生型多肽)具有至少约60％、至少约65％、至少约70％、至少约75％、至少约80％、至少约85％、至少约90％、至少约95％同一性或至少约99％同一性的多肽；或由与参考多核苷酸(例如野生型多核苷酸)具有至少约70％、至少约75％、至少约80％、至少约85％、至少约90％、至少约95％的同一性、至少约97％的序列同一性或至少约99％的序列同一性的多核苷酸编码的多肽。

“同源性”或“同一性”或“相似性”是指两个肽之间或两个核酸分子之间的序列相似性。同一性百分比可以通过比较每个序列中的位置来确定，所述序列可以为了比较的目的而比对。当被比较序列中的位置被相同的碱基或氨基酸占据时，则分子在该位置是相同的。序列之间的同一性程度取决于共享的匹配位置数目。“无关”或“非同源”序列与本公开的序列之一共享小于40％的同一性、小于25％的同一性。通过将所述核酸或氨基酸序列导入ClustalW(可从https://genome.jp/tools-bin/clustalw/获得)并使用该ClustalW，可以确定本文提供的核酸或氨基酸序列的比对和序列同一性百分比。例如，使用Gonnet(对于蛋白质)权重矩阵产生用于进行本文发现的蛋白质序列比对(例如，图20-23)的ClustalW参数。在实施方案中，使用ClustalW(用于DNA)权重矩阵产生用于使用本文发现的核酸序列进行核酸序列比对的ClustalW参数。

如本文所用，氨基酸修饰可以是氨基酸取代、氨基酸缺失或氨基酸插入。氨基酸取代可以是保守氨基酸取代或非保守氨基酸取代。保守置换(也称为保守突变、保守置换或保守变异)是蛋白质中的氨基酸置换，其将给定氨基酸改变为具有相似生化性质(例如电荷、疏水性或大小)的不同氨基酸。如本文所用，“保守变异”是指氨基酸残基被另一个生物学上相似的残基置换。保守变异的实例包括一个疏水残基如异亮氨酸、缬氨酸、亮氨酸或甲硫氨酸取代另一个；或一个带电荷或极性残基取代另一个，如精氨酸取代赖氨酸，谷氨酸取代天冬氨酸，谷氨酰胺取代天冬酰胺等。保守取代的其它示例性实例包括以下变化：丙氨酸变为丝氨酸；天冬酰胺变为谷氨酰胺或组氨酸；天冬氨酸变为谷氨酸；半胱氨酸变为丝氨酸；甘氨酸变为脯氨酸；组氨酸变为天冬酰胺或谷氨酰胺；赖氨酸变为精氨酸、谷氨酰胺或谷氨酸；苯丙氨酸变为酪氨酸，丝氨酸变为苏氨酸；苏氨酸变为丝氨酸；色氨酸变为酪氨酸；酪氨酸变为色氨酸或苯丙氨酸；等等。

如本文所用，术语“载体”指包含完整复制子、基本上由完整复制子组成或由完整复制子组成的核酸，使得当例如通过转染、感染或转化过程将载体置于细胞内时，载体可以被复制。本领域理解，一旦进入细胞，载体可以作为染色体外(附加型)元件复制或者可以整合到宿主细胞染色体中。载体可以包括来源于逆转录病毒、腺病毒、疱疹病毒、杆状病毒、修饰的杆状病毒、乳多空病毒或其它修饰的天然存在的病毒的核酸。用于递送核酸的示例性非病毒载体包括裸DNA；与阳离子脂质(单独或与阳离子聚合物结合)复合的DNA；阴离子和阳离子脂质体；DNA-蛋白质复合物和颗粒，其包含与阳离子聚合物(如异质聚赖氨酸、限定长度的寡肽和聚乙烯亚胺)凝聚的，在一些情况下包含在脂质体中的DNA、基本上由其组成或由其组成，所述阳离子聚合物例如异源聚赖氨酸、限定长度的寡肽和聚乙烯亚胺；以及包含、基本上由或由病毒和聚赖氨酸-DNA病毒和聚赖氨酸-DNA组成的三元复合物的使用。

关于一般重组技术，含有启动子和克隆位点的载体是本领域公知的，其中多核苷酸可以可操作地连接到所述克隆位点中。这些载体能够在体外或体内转录RNA，并且可以从诸如Agilent Technologies(Santa Clara,Calif)和Promega Biotech(Madison,Wis.)的来源商购获得。为了优化表达和/或体外转录，可能需要去除、添加或改变克隆的转基因的5'和/或3'非翻译部分，以消除额外的、潜在的不适当的可选翻译起始密码子或或可能在转录或翻译层面干扰或降低表达的其它序列。或者，可将共有核糖体结合位点插入紧靠起始密码子的5'以增强表达。

“病毒载体”定义为重组产生的病毒或病毒颗粒，其含有将在体内、离体或体外递送至宿主细胞中的多核苷酸。病毒载体的实例包括逆转录病毒载体、AAV载体、慢病毒载体、腺病毒载体、甲病毒载体等。甲病毒载体，例如基于塞姆利基森林(Semliki Forest)病毒的载体和基于辛德毕斯(Sindbis)病毒的载体，也已经被开发用于基因疗法和免疫疗法。参见，例如Schlesinger和Dubensky(1999)Curr.Opin.Biotechnol.5:434-439和Ying等。(1999)Nat.Med.5(7):823-827。

如本文所用，术语“重组表达系统”或“重组载体”是指用于表达通过重组形成的某些遗传物质的遗传构建体。

“基因递送载体”定义为任何可以携带插入的多核苷酸进入宿主细胞的分子。基因递送载体的实例是脂质体、胶束、生物相容的聚合物，包括天然聚合物和合成聚合物；脂蛋白；多肽；多糖；脂多糖；人工病毒包膜；金属颗粒；细菌；病毒，如杆状病毒、腺病毒和逆转录病毒；噬菌体、粘粒、质粒和真菌载体；和本领域通常使用的其它重组载体，其已经被描述用于在多种真核和原核宿主中表达，并且可以用于基因疗法以及用于简单蛋白质表达。也包含、基本上由或由靶向抗体或其片段组成的脂质体可用于本文公开的方法中。除了将多核苷酸递送至细胞或细胞群之外，可以通过非限制性蛋白转染技术将本文所述的蛋白直接引入细胞或细胞群，或者，可以增强本文公开的蛋白的表达和/或促进其活性的培养条件是其他非限制性技术。

本文公开的多核苷酸可以使用基因递送载体递送至细胞或组织。本文所用的“基因递送”、“基因转移”、“转导”等是指将外源多核苷酸(有时称为“转基因”)导入宿主细胞，而与导入所用的方法无关。这些方法包括多种众所周知的技术，例如载体介导的基因转移(通过例如病毒感染/转染，或多种其它基于蛋白质或基于脂质的基因递送复合物)以及促进“裸”多核苷酸递送的技术(例如电穿孔、“基因枪”递送和用于多核苷酸引入的多种其它技术)。导入的多核苷酸可以稳定或瞬时维持在宿主细胞中。稳定维持通常需要引入的多核苷酸含有与宿主细胞相容的复制起点，或整合到宿主细胞的复制子中，例如染色体外复制子(例如质粒)或核或线粒体染色体。已知许多载体能够介导基因转移到哺乳动物细胞中，如本领域已知和本文所述。

“质粒”是通常与染色体DNA分离并能够独立于染色体DNA复制的DNA分子。在许多情况下，它是环状的和双链的。质粒提供了在微生物群体内水平基因转移的机制，并且通常在给定的环境状态下提供选择性优势。质粒可以携带在竞争性环境小生境中提供对天然存在的抗生素的抗性的基因，或可选地，产生的蛋白质可以在类似的环境下充当毒素。本领域已知，尽管质粒载体通常以染色体外环状DNA分子存在，但也可以设计质粒载体以随机或靶向方式稳定整合到宿主染色体中，并且可以使用环状质粒或在引入宿主细胞之前已经线性化的质粒完成这种整合。

基因工程中使用的“质粒”被称为“质粒载体”。许多质粒可商购获得用于这样的用途。将待复制的基因插入到质粒的拷贝中，所述质粒含有使细胞对特定抗生素具有抗性的基因和多克隆位点(MCS或多接头)，所述多克隆位点是含有若干个常用限制性位点(允许在该位置容易地插入DNA片段)的短区。质粒的另一个主要用途是产生大量的蛋白质。在这种情况下，研究人员培养含有携带目标基因的质粒的细菌或真核细胞，所述目标基因可被诱导以从插入的基因产生大量蛋白质。

在由DNA病毒载体如腺病毒(Ad)或腺相关病毒(AAV)介导基因转移的方面，载体构建体是指包含、基本上由或由病毒基因组或其部分以及转基因组成的多核苷酸。

本文所用的术语“腺相关病毒”或“AAV”是指与该名称相关的病毒类别的成员，并且属于依赖性细小病毒(Dependoparvovirus)属，细小病毒(Parvoviridae)科。腺相关病毒是一种单链DNA病毒，它只在细胞中生长，其中某些功能是由共同感染的辅助病毒提供的。AAV的一般信息和综述可参见例如Carter,1989,Handbook of Parvoviruses,第1卷，第169-228页，以及Berns,1990,Virology，第1743-1764页，Raven Press(纽约)。完全期望这些综述中描述的相同原理将适用于在综述的出版日期之后表征的其它AAV血清型，因为众所周知，各种血清型在结构上和功能上非常密切相关，甚至在遗传水平上也是如此。(参见，例如，Blacklowe,1988年,Parvoviruses and Human Disease第165-174页,J.R.Pattison编；和Rose,Comprehensive Virology 3:1-61(1974))。例如，所有AAV血清型显然都表现出非常相似的由同源rep基因介导的复制特性；并且都携带三种相关的衣壳蛋白，例如在AAV2中表达的那些。相关性程度进一步由异源双链分析提示，其显示了血清型之间沿基因组长度的广泛交叉杂交；以及在对应于“反向末端重复”(ITR)的末端存在类似的自退火区段。相似的感染性模式也表明每种血清型的复制功能处于相似的调控下。已知该病毒的多种血清型适于基因递送；所有已知的血清型可以感染来自各种组织类型的细胞。至少11种顺序编号的AAV血清型是本领域已知的。可用于本文所公开方法的非限制性示例性血清型包括11种血清型中的任一种，例如AAV2、AAV8、AAV9或变体血清型，例如AAV-DJ和AAV PHP.B。AAV颗粒包含下列三种主要病毒蛋白，基本上由下列三种主要病毒蛋白组成，或由下列三种主要病毒蛋白组成：VP1、VP2和VP3。在实施方案中，AAV指血清型AAV1、AAV2、AAV4、AAV5、AAV6、AAV7、AAV8、AAV9、AAV10、AAV11、AAV12、AAV13、AAVPHP.B或AAVrh74。

本文所用的“AAV载体”指包含一个或多个异源核酸(HNA)序列和一个或多个AAV反向末端重复(ITR)、基本上由其组成或由其组成的载体。当存在于提供rep和cap基因产物功能性的宿主细胞中时，这种AAV载体可被复制并包装到感染性病毒颗粒中；例如通过转染宿主细胞。在实施方案中，AAV载体含有启动子、编码至少一种蛋白质或RNA的至少一种核酸、和/或包装到感染性AAV颗粒的侧翼ITR内的增强子和/或终止子。包壳的核酸部分可称为AAV载体基因组。含有AAV载体的质粒也可含有用于制备用途的元件，例如抗生素抗性基因等，但这些不被包壳，因此不形成AAV颗粒的一部分。

如本文所用，术语“病毒衣壳”或“衣壳”是指病毒颗粒的蛋白质外壳或衣壳。衣壳的功能是包壳、保护、转运病毒基因组，并将其释放到宿主细胞中。衣壳通常由蛋白质的寡聚结构亚基(“衣壳蛋白”)组成。如本文所用，术语“包壳”是指被包含在病毒衣壳内。AAV的病毒衣壳由三种病毒衣壳蛋白的混合物组成：VP1、VP2和VP3。VP1、VP2和VP3的混合物含有60个单体，它们以T＝1二十面体对称排列，比例为1:1:10(VP1:VP2:VP3)或1:1:20(VP1:VP2:VP3)，如Sonntag F等(June 2010)所述。"A viral assembly factor promotes AAV2capsid formation in the nucleolus".Proceedings of the National Academy ofSciences of the United States of America.107(22):10220–5和Rabinowitz JE,Samulski RJ(December 2000)."Building a better vector:the manipulation of AAVvirions".Virology.278(2):301–8，其中每一篇以引用方式整体并入本文中。

“AAV病毒粒子”或“AAV病毒颗粒”或“AAV病毒载体”或“AAV载体颗粒”或“AAV颗粒”指由至少一种AAV衣壳蛋白和包壳的多核苷酸AAV载体组成的病毒颗粒。因此，AAV载体颗粒的生产必然包括AAV载体的生产，因为这样的载体包含在AAV载体颗粒中。

如本文所用，关于病毒或质粒的术语“辅助者”是指用于提供本文公开的任一种AAV载体复制和包装所必需的额外组分的病毒或质粒。辅助病毒编码的组分可以包括病毒粒子组装、包壳、基因组复制和/或包装所需的任何基因。例如，辅助病毒或质粒可编码病毒基因组复制所必需的酶。适合与AAV构建体一起使用的辅助病毒和质粒的非限制性实例包括pHELP(质粒)、腺病毒(病毒)或疱疹病毒(病毒)。在实施方案中，pHELP质粒可以是pHELPK质粒，其中氨苄青霉素表达盒与卡那霉素表达盒交换；pHELPK具有SEQ ID NO:92所示的序列。

如本文所用，包装细胞(或辅助细胞)是用于产生病毒载体的细胞。生产重组AAV病毒载体需要反式提供的Rep和Cap蛋白以及来自腺病毒的帮助AAV复制的基因序列。在一些方面，包装/辅助细胞含有稳定整合到细胞基因组中的质粒。在其它方面，包装细胞可以被瞬时转染。通常，包装细胞是真核细胞，例如哺乳动物细胞或昆虫细胞。

如本文所用，报告蛋白是一种可检测的蛋白，其与启动子可操作地连接以测定启动子的表达(例如，组织特异性和/或强度)。在一些方面，报告蛋白可以可操作地连接至多肽。在一些方面，报告蛋白可用于监测DNA递送方法、启动子和增强子元件的功能鉴定和表征、翻译和转录调节、mRNA加工和蛋白质：蛋白质相互作用。报告蛋白的非限制性实例是β-半乳糖苷酶；荧光蛋白，例如绿色荧光蛋白(GFP)或红色荧光蛋白(RFP)；荧光素酶；谷胱甘肽S-转移酶；和麦芽糖结合蛋白。

“组合物”旨在意指活性多肽、多核苷酸或抗体与另一种惰性(例如可检测标记)或活性(例如基因递送载体)化合物或组合物的组合。

“药物组合物”意在包括活性多肽、多核苷酸或抗体与惰性或活性载体如固体支持物的组合，使得组合物适于体外、体内或离体诊断或治疗用途。

如本文所用，术语“药学上可接受的载体”涵盖任何标准药物载体，如磷酸盐缓冲盐水溶液、水和乳液，如油/水或水/油乳液，及各种类型的润湿剂。组合物还可以包括稳定剂和防腐剂。载体、稳定剂和佐剂的实例，参见Martin (1975)Remington's Pharm.Sci.第15版(Mack Publ.Co.,Easton)。

诊断或治疗的“受试者”是细胞或动物，例如哺乳动物或人。受试者不限于特定物种，包括接受诊断或治疗的非人动物和接受感染或动物模型的那些动物，包括但不限于猿、鼠、大鼠、犬或兔类物种，以及其它家畜、运动类动物或宠物。在实施方案中，所述受试者是人。

本文所用术语“组织”是指活的或死亡的生物体的组织或任何来源于或设计成模仿活的或死亡的生物体的组织。所述组织可以是健康的、患病的和/或具有基因突变。生物组织可以包括任何单个组织(例如，可以相互连接的细胞的集合)，或构成器官或生物体的身体的部分或区域的一组组织。该组织可以包含、基本上由或由均质的细胞材料组成，或者它可以是复合结构，例如在包括胸腔的身体区域中发现的结构，例如可以包括肺组织、骨骼组织和/或肌肉组织。示例性组织包括但不限于源自肝脏、肺、甲状腺、皮肤、胰腺、血管、膀胱、肾脏、脑、胆道、十二指肠、腹主动脉、髂静脉、心脏和肠的那些，包括其任何组合。

如本文所用，受试者中疾病的“治疗”是指(1)预防受试者中发生的症状或疾病，所述受试者易患或尚未表现出疾病的症状；(2)抑制疾病或阻止其发展；或(3)改善或引起疾病或疾病症状的消退。如本领域所理解的，“治疗”是用于获得有益或期望结果的方法，包括临床结果。出于本技术的目的，有益或期望的结果可以包括一种或多种，但不限于，减轻或改善无论可检测的还是不可检测的一种或多种症状、减轻病状(包括疾病)的程度、病状(包括疾病)的稳定(即，不恶化)状态、延缓或减缓病状(包括疾病)、进展、改善或减轻病状(包括疾病)、状态和缓解(无论部分或全部)。

本文所用术语“有效量”旨在意指足以达到所需效果的量。在治疗或预防应用的情况下，有效量将取决于所讨论的病症的类型和严重性以及个体受试者的特征，例如一般健康、年龄、性别、体重和对药物组合物的耐受性。在基因疗法的背景下，在实施方案中，有效量是足以导致在受试者中缺陷的基因恢复部分或全部功能的量。在其它一些实施方案中，AAV病毒颗粒的有效量是足以导致基因在受试者中表达的量。在实施方案中，所述有效量是在有需要的受试者中增加半乳糖代谢所需的量。熟练的技术人员将能够根据这些和其它因素确定合适的量。

在实施方案中，有效量将取决于所讨论的应用的大小和性质。它还取决于目标受试者的性质和敏感性以及使用的方法。本领域技术人员将能够基于这些和其它考虑来确定有效量。根据实施方案，有效量可以包括组合物的一次或多次施用、基本上由组合物的一次或多次施用组成或由组合物的一次或多次施用组成。

如本文所用，术语“施用”旨在表示将物质递送至受试者，诸如动物或人。施用可以在整个治疗过程中以一个剂量、连续或间歇地进行。确定最有效的施用方式和剂量的方法是本领域技术人员已知的，并且将随用于治疗的组合物、治疗目的以及被治疗的受试者的年龄、健康或性别而变化。可以进行单次或多次施用，剂量水平和模式由治疗医师选择，或者在宠物和其它动物的情况下，由治疗兽医选择。

AAV的结构和功能

AAV是复制缺陷型细小病毒，其单链DNA基因组的长度为约4.7kb，包括两个145个核苷酸的反向末端重复(ITR)。AAV有多种血清型。AAV血清型的基因组的核苷酸序列是已知的。例如，AAV-1的完整基因组提供于GenBank登记号NC_002077；AAV-2的完整基因组提供于GenBank登记号NC_001401和Srivastava等，J.Virol.,45:555-564(1983)；AAV-3的完整基因组提供于GenBank登录号NC_l829；AAV-4的完整基因组提供于GenBank登录号NC_001829；AAV-5基因组提供于GenBank登录号AF085716；AAV-6的完整基因组提供于GenBank登记号NC_001862；AAV-7和AAV-8基因组的至少部分分别提供于GenBank登录号AX753246和AX753249；AAV-9基因组提供于Gao等，J.Virol.,78:6381-6388(2004)；AAV-10基因组提供于Mol.Ther.,13(1):67-76(2006)；并且AAV-11基因组提供于Virology,330(2):375-383(2004)。AAV rh.74基因组的序列在美国专利9,434,928中提供，其以引用方式整体并入本文中。美国专利9,434,928也提供了衣壳蛋白和自身互补基因组的序列。在一个方面，基因组是自身互补的基因组。AAV ITR中含有指导病毒DNA复制(rep)、包壳/包装和宿主细胞染色体整合的顺式作用序列。三个AAV启动子(相对图谱位置命名为p5、p19和p40)驱动编码rep和cap基因的两个AAV内部开放阅读框的表达。两个rep启动子(p5和p19)与单个AAV内含子(在核苷酸2107和2227)的差异剪接结合，导致从rep基因产生四种rep蛋白(rep 78、rep68、rep 52和rep 40)。Rep蛋白具有多种酶特性，这些特性最终负责复制病毒基因组。

cap基因从p40启动子表达，并编码三种衣壳蛋白VP1、VP2和VP3。选择性剪接和非共有翻译起始位点负责产生三种相关的衣壳蛋白。更具体地，在转录翻译VP1、VP2和VP3各自的单个mRNA后，可以以两种不同的方式剪接：可以切除更长或更短的内含子，导致形成两个mRNA库：2.3kb和2.6kb长的mRNA库。通常优选较长的内含子，因此2.3kb长的mRNA可被称为主要剪接变体。该形式缺少VP1蛋白合成从其开始的第一AUG密码子，导致VP1蛋白合成的总体水平降低。保留在主要剪接变体中的第一个AUG密码子是VP3蛋白的起始密码子。然而，在同一开放读码框中该密码子的上游是ACG序列(编码苏氨酸)，其被最佳的Kozak(翻译起始)背景包围。这导致低水平合成VP2蛋白，其实际上是具有额外N末端残基的VP3蛋白，如VP1，如Becerra SP等(1985年12月)中所述。"Direct mapping of adeno-associatedvirus capsid proteins B and C:a possible ACG initiation codon".Proceedings ofthe National Academy of Sciences of the United States of America.82(23)：7919-23，Cassinotti P等，(1988年11月)。"Organization of the adeno-associated virus(AAV)capsid gene:mapping of aminor spliced mRNA coding for virus capsidprotein 1".Virology.167(1):176–84,Muralidhar S等，(1994年1月)."Site-directedmutagenesis of adeno-associated virus type 2structural protein initiationcodons:effects on regulation of synthesis and biological activity".Journal ofVirology.68(1)：170-6，以及Trempe JP，Carter BJ(1988年9月)。"Alternate mRNAsplicing is required for synthesis of adeno-associated virus VP1 capsidprotein".Journal of Virology.62(9)：3356-63，其中每一篇以引用方式并入本文中。单个共有poly-A位点位于AAV基因组的图谱位置95。AAV的生命周期和遗传学综述于Muzyczka，Current Topics in Microbiology and Immunology,158:97-129(1992)。

每个VP1蛋白含有VP1部分、VP2部分和VP3部分。VP1部分是VP1蛋白的N-末端部分，其是VP1蛋白所特有的。VP2部分是VP1蛋白中存在的氨基酸序列，也在VP2蛋白的N-末端部分发现。VP3部分和VP3蛋白具有相同的序列。VP3部分是VP1蛋白的C端部分，其与VP1和VP2蛋白共有。参见图30。

VP3蛋白可进一步分成离散可变表面区I-IX(VR-I-IX)。每种可变表面区(VR)可包含或含有特定氨基酸序列，所述特定氨基酸序列单独或与其它VR中每一种的特定氨基酸序列组合可赋予特定血清型独特感染表型(例如，相对于其它AAV血清型，抗原性降低、转导改善和/或组织特异性向性)，如DiMatta等“Structural Insight into the UniqueProperties of Adeno-Associated Virus Serotype 9”J.Virol.,Vol.86(12):6947-6958,2012年6月，其内容以引用方式并入。

AAV具有独特的特征，使其作为载体在例如基因疗法中向细胞递送外源DNA具有吸引力。培养物中细胞的AAV感染是非致细胞病变的，而人类和其它动物的天然感染是沉默的和无症状的。此外，AAV感染许多哺乳动物细胞，使得有可能在体内靶向许多不同组织。此外，AAV转导缓慢分裂和非分裂细胞，并且可作为转录活性核附加体(染色体外元件)基本上持续这些细胞的寿命。AAV前病毒基因组作为克隆的DNA插入质粒中，这使得重组基因组的构建可行。此外，由于指导AAV复制和基因组包壳的信号包含在AAV基因组的ITR内，一些或所有内部约4.3kb的基因组(编码复制和结构衣壳蛋白，rep-cap)可被外源DNA取代以产生AAV载体。rep和cap蛋白可以以反式提供。AAV的另一个显著特征是它是一种极其稳定和旺盛的病毒。它容易经受住灭活腺病毒所用的条件(56-65℃数小时)，使得AAV的冷藏不太关键。AAV甚至可被冻干。最后，AAV感染的细胞对双重感染没有抗性。

多项研究已证明肌肉中长期(＞1.5年)重组AAV介导的蛋白质表达。参见Clark等，Hum Gene Ther,8:659-669(1997)；Kessler等，Proc Nat.Acad Sc.USA,93:14082-14087(1996)；和Xiao等，J Virol,70:8098-8108(1996)。还参见Chao等，Mol Ther,2:619-623(2000)和Chao等，Mol Ther,4:217-222(2001)。此外，由于肌肉高度血管化，重组AAV转导导致肌肉注射后体循环中转基因产物的出现，如Herzog等，Proc Natl Acad Sci USA,94:5804-5809(1997)以及Murphy等,Proc Natl Acad Sci USA,94:13921-13926(1997)。此外，Lewis等J Virol,76:8769-8775(2002)证实骨骼肌纤维具有正确抗体糖基化、折叠和分泌的必要细胞因子，表明肌肉能够稳定表达分泌的蛋白质治疗剂。本发明的重组AAV(rAAV)基因组包含编码治疗性蛋白质(例如CFTR)的核酸分子和侧接该核酸分子的一个或多个AAVITR，基本上由其组成，或由其组成。rAAV基因组中的AAV DNA可来自重组病毒可源自的任何AAV血清型，包括但不限于AAV血清型AAV-1、AAV-2、AAV-3、AAV-4、AAV-5、AAV-6、AAV-7、AAV-8、AAV-9、AAV-10、AAV-11、AAV-12、AAV-13、AAV PHP.B和AAV rh74。假型rAAV的制备公开于例如WO2001083692中。也考虑了其它类型的rAAV变体，例如具有衣壳突变的rAAV。参见，例如Marsic等，Molecular Therapy,22(11):1900-1909(2014)。各种AAV血清型的基因组的核苷酸序列是本领域已知的。

AAV载体颗粒、衣壳蛋白和AAV载体

本文提供了AAV载体颗粒、AAV载体和衣壳蛋白，其具有期望的组织特异性并且可用于递送多种治疗有效载荷，包括可用于治疗疾病的核酸和蛋白质。

AAV衣壳蛋白

本公开提供了具有高基因转移效率和增加的组织向性的AAV颗粒。AAV载体递送目前依赖于使用血清型选择用于基于病毒的天然向性的组织靶向或通过直接注射到靶组织中。如果需要全身递送以实现最大治疗益处，则血清型选择是与组织特异性启动子组合的组织靶向的唯一可用选项。因此，许多目前可用的AAV载体对于基因疗法是次优的。

本发明提供了AAV衣壳蛋白序列，其赋予包含它们的AAV衣壳高基因转移效率和增加的组织特异性。在实施方案中，本文提供的AAV衣壳序列使用图1所示的AAV衣壳生成平台生成。

在实施方案中，VP1衣壳蛋白包含表1中列出的氨基酸序列中的任一个，或与表1中列出的氨基酸序列中的任一个相比突变、缺失或添加至多1、2、3、4、5、6、7、8、9或10个氨基酸的序列。在多个方面，与这些序列相比，可突变、缺失或添加至多20个氨基酸、至多30个氨基酸或至多40个氨基酸，在实施方案中，VP1衣壳蛋白由表1中列出的核酸序列中的任一个，或与由表1中列出的核酸序列中的任一个相比具有至多5个、至多10个、至多30个或至多60个核苷酸变化的序列编码。

表1：VP1衣壳蛋白

氨基酸SEQ ID NO	NA SEQ ID NO:	AAV衣壳名称
			1	98	AAV 110
2	15	AAV 204
			3	18	AAV 214
30	19	AAV 214A
			31	20	AAV 214e
32	21	AAV 214e8
			33	22	AAV 214e9
34	23	AAV 214e10
			49	47	AAV ITB102_45
84	82	AAV 214AB

在实施方案中，AAV VP1蛋白包含、由或基本上由SEQ ID NO:1-3、30-34、49或84的氨基酸序列，或具有至多1、2、3、4、5、6、7、8、9或10个不同于SEQ ID NO:1-3、30-34、49或84的氨基酸的序列组成。还提供了编码这些VP1蛋白的多核苷酸。在实施方案中，编码VP1蛋白的多核苷酸包含、由或基本上由SEQ ID NO:15、18-23、47、82和98的序列，或与SEQ ID NO:15、18-23、47、82和98的序列相比具有至多5个、至多10个、至多30个核苷酸变化的序列组成。

在实施方案中，AAV衣壳序列是AAV-110衣壳蛋白(SEQ ID NO:1)、AAV 204衣壳蛋白(SEQ ID NO:2)、AAV 214衣壳蛋白(SEQ ID NO:3)或AAV ITB102_45衣壳蛋白(SEQ IDNO:49)。在实施方案中，AAV衣壳蛋白是AAV 214衣壳蛋白的变体。在实施方案中，AAV衣壳蛋白是AAV214A(SEQ ID NO:30)、AAV-214-AB(SEQ ID NO:84)、AAV214e(SEQ ID NO:31)、AAV214e8(SEQ ID NO:32)、AAV214e9(SEQ ID NO:33)或AAV214e10(SEQ ID NO:34)。

示例性VP2和VP3蛋白的序列提供于表2和表3中。给定VP2和VP3序列，可通过与完整的VP1蛋白序列比对来测定VP1部分。

表2：VP2衣壳蛋白

氨基酸SEQ ID NO	名称
		35	214
36	214A
		37	214e
38	214e8
		39	214e9
40	214e10
		85	214AB
50	ITB102_45

ITB102_45的示例性核酸是SEQ ID NO:47。其它衣壳VP2部分的示例性核酸可衍生自VP1衣壳蛋白核酸的相应部分。

表3：VP3衣壳蛋白

AAV214、AAV214e、AAV214e8、AAV214e9、AAV214e10的VP3蛋白具有相同的氨基酸(SEQ ID NO:41)和核酸(SEQ ID NO:24)序列。

在实施方案中，AAV VP2蛋白包含、由或基本上由SEQ ID NO:35-40、50或85的氨基酸序列，或具有至多1、2、3、4、5、6、7、8、9或10个不同于SEQ ID NO:35-40、50或85的氨基酸的序列组成。还提供了编码这些VP2蛋白的多核苷酸。在实施方案中，编码VP2蛋白的多核苷酸包含、由或基本上由SEQ ID NO:47的序列，或与SEQ ID NO:47的序列相比具有至多5个、至多10个、至多30个核苷酸变化的序列组成。

在实施方案中，AAV VP3蛋白包含、由或基本上由SEQ ID NO:17、41-46、51或86的氨基酸序列，或具有至多1、2、3、4、5、6、7、8、9或10个不同于SEQ ID NO:17、41-46、51或86的氨基酸的序列组成。还提供了编码这些VP3蛋白的多核苷酸。在实施方案中，编码蛋白质的多核苷酸包含、由或基本上由SEQ ID NO:16、24-29、48和83的序列，或与SEQ ID NO:16、24-29、48和83的序列相比具有至多5个、至多10个、至多30个核苷酸变化的序列组成。

在实施方案中，AAV衣壳蛋白是嵌合蛋白。在实施方案中，本文公开的AAV衣壳蛋白的VP1、VP2或VP3部分可被来自本文公开的不同AAV衣壳蛋白的VP1、VP2或VP3部分替代。

在实施方案中，本文提供了一种AAV衣壳蛋白，其包含在氨基酸129处的亮氨酸残基、在氨基酸586处的天冬酰胺残基和在氨基酸723处的谷氨酸残基，其中AAV衣壳蛋白中的氨基酸位置相对于SEQ ID NO:2的氨基酸序列中的氨基酸位置进行编号。在一些情况下，蛋白质包含SEQ ID NO:2的氨基酸序列。在其它情况下，这些氨基酸可以被引入到其它衣壳蛋白中。

在实施方案中，本文提供了AAV VP1衣壳蛋白，其包含VP1部分、VP2部分和VP3部分，其中所述VP1部分包含在氨基酸129处的亮氨酸(L)残基，其中所述VP2部分包含在氨基酸157处的苏氨酸(T)或天冬酰胺(N)残基和在氨基酸162处的赖氨酸(K)或丝氨酸(S)残基，并且其中所述VP3部分包含在氨基酸223处的天冬酰胺(N)残基、在氨基酸224处的丙氨酸(A)残基、在氨基酸272处的组氨酸(H)残基、在氨基酸410处的苏氨酸(T)残基、在氨基酸724处的组氨酸(H)残基和在氨基酸734处的脯氨酸(P)残基，其中所述AAV衣壳蛋白衣壳中的氨基酸位置相对于SEQ ID NO:3的氨基酸序列中的氨基酸位置进行编号(即VP1衣壳亚基编号)。

在实施方案中，VP1部分还包含在氨基酸24处的天冬氨酸(D)或丙氨酸(A)残基，其中AAV衣壳蛋白中的氨基酸位置相对于SEQ ID NO:3的氨基酸序列中的氨基酸位置进行编号。在实施方案中，VP2部分还包含下列中的一者或多者：(i)在氨基酸148处的脯氨酸(P)残基；(ii)在氨基酸152处插入的精氨酸(R)残基；(iii)在氨基酸168处的精氨酸(R)残基；(iv)在氨基酸189处的异亮氨酸(I)残基；和(v)在氨基酸200处的丝氨酸(S)残基，其中AAV衣壳蛋白中的氨基酸位置相对于SEQ ID NO:3的氨基酸序列中的氨基酸位置进行编号。

在实施方案中，在公开的VP3部分衣壳蛋白中的一个或多个可变区I-IX(参见图30)可被去除并用可变区替换。下表中确定了合适的替代方案。这些序列的位置以及其它选择的同一性可通过与SEQ ID NO:41比对来鉴定，如图30所示。在实施方案中，一个或多个VR可以具有1、2或3个氨基酸的插入。在实施方案中，一个或多个VR可以具有1、2或3个氨基酸的缺失。

本公开提供了编码本文公开的AAV衣壳蛋白中的任一种的核酸。本公开还提供了包含本文公开的核酸中的任一种的载体。

在实施方案中，AAV是AAV9血清型。可以使用替代血清型或经修饰的衣壳病毒来优化神经元向性。可选的载体包括：用于比标准AAV9更高的神经元向性的修饰的AAV9血清型载体，例如PHP.B，其使用Cre-lox重组系统来鉴定神经元靶向载体。或者，AAV9 PHP.B具有VP1的经修饰的氨基酸498(从天冬酰胺变为赖氨酸)以降低肝向性。具有突变的几个氨基酸的AAVrh74的其它变体可用于非常广泛的组织向性，包括脑。

AAV载体

AAV载体提供被包壳到AAV载体颗粒中的核酸，所述AAV载体颗粒包括参与控制核酸在受试者中表达的元件以及促进包壳的ITR。在实施方案中，本文公开的AAV载体包含至少一种异源核酸(HNA)序列，该序列在受试者的细胞中表达时可有效治疗疾病或病症。在实施方案中，HNA序列包含转基因。在实施方案中，AAV载体包含至少一个ITR序列和至少一个转基因。在实施方案中，转基因编码治疗性蛋白质或治疗性RNA。

在实施方案中，宿主细胞中转基因表达的控制可由AAV载体内包含的调节元件调节，包括启动子序列和poly-A位点。在实施方案中，AAV载体也可编码信号肽。在实施方案中，AAV载体具有5’和3’反向末端重复(ITR)。5’ITR位于启动子的上游，启动子又位于转基因的上游。在实施方案中，5’和3’ITR具有相同的序列。在实施方案中，它们具有不同的序列。在实施方案中，本公开的AAV载体可在5’至3’取向上包含第一(5’)ITR、启动子、转基因、poly-A位点和第二(3’)ITR。

在实施方案中，AAV载体具有SEQ ID NO:88(pA_CF1)、SEQ ID NO:89(pA_CF3)、SEQID NO:90(pA_CF5)或SEQ ID NO:91(pA_CF7)所示的核苷酸序列。这些载体含有下列组分：

在实施方案中，HNA(例如包含转基因的HNA)与组成型启动子可操作地连接。组成型启动子可以是本领域已知和/或本文提供的任何组成型启动子。在实施方案中，组成型启动子包含、基本上由或由劳斯肉瘤病毒(RSV)LTR启动子(任选地与RSV增强子一起)、巨细胞病毒(CMV)启动子、SV40启动子、二氢叶酸还原酶启动子、β-肌动蛋白启动子、磷酸甘油激酶(PGK)启动子、U6启动子、H1启动子、杂合鸡β肌动蛋白启动子、MeCP2启动子、H1启动子、U1a启动子、mMeP418启动子、mMeP426启动子、最小MeCP2启动子、CAG启动子或EF1启动子组成。本领域已知，可以修饰这些启动子的核苷酸序列以提高或降低mRNA转录的效率。参见，例如Gao等(2018)Mol.Ther.:Nucleic Acids 12:135-145(修饰7SK、U6和H1启动子的TATA盒以消除RNA聚合酶III转录并刺激RNA聚合酶II依赖性mRNA转录)。在实施方案中，HNA序列与组织特异性控制启动子或诱导型启动子可操作地连接。在实施方案中，组织特异性控制启动子是中枢神经系统(CNS)细胞特异性启动子、肺特异性启动子、皮肤特异性启动子、肌肉特异性启动子、肝特异性启动子、眼异性启动子(例如VMD2或mRho启动子)。

在实施方案中，启动子可包含、基本上由或由具有SEQ ID NO:96(小鼠U1启动子)或SEQ ID NO:97(H1启动子)序列的多核苷酸组成。在实施方案中，启动子是U1a或U1b启动子、EF1启动子或CBA(鸡β-肌动蛋白)。在实施方案中，启动子可以包含、基本上由或由表5中列出的核酸序列中的任一个，或与表5中列出的核酸序列中的任一个相比具有至多5个、至多10个或至多30个核苷酸变化的序列组成。

表5：

在实施方案中，HNA序列与另外的调节元件可操作地连接。所述额外的调节元件可以是土拨鼠肝炎病毒转录后调节元件(“WPRE”)。在实施方案中，AAV载体可包含适于载体在细菌宿主中生长和培养的调节组分，用于载体生产目的。例如，载体可以包含抗生素抗性基因，和细菌中质粒的维持，以及控制细菌中蛋白质表达的相关调节元件。

在实施方案中，HNA序列与poly-A位点可操作地连接。聚腺苷酸化位点包含、基本上由或由MeCP2 poly-A位点、视黄醇脱氢酶1(RDH1)poly-A位点、牛生长激素(BGH)poly-A位点、SV40 poly-A位点、SPA49 poly-A位点、sNRP-TK65 poly-A位点、sNRP poly-A位点或TK65 poly-A位点组成。示例性SPA49 poly-A序列描述于Ostedgaard等，Proc.Nat’lAcad.Sci.USA(2005年2月22日)102:2952-2957，其以引用方式并入本文汇中。

异源核酸(HNA)

本文公开的AAV载体感染一种或多种异源核酸(HNA)并将其递送至靶组织。在实施方案中，HNA序列在靶组织的细胞中被转录并且任选地被翻译。

在一些情况下，HNA编码反义RNA、微RNA、siRNA或引导RNA(gRNA)。CRISPR技术已经用于靶向活细胞的基因组以进行修饰。Cas9蛋白是一种大的酶，其必须被有效地递送至靶组织和细胞以通过CRISPR系统介导基因修复，并且目前的CRISPR/Cas9基因修正方案具有许多缺点。Cas9的长期表达可引发宿主免疫应答。由于包装限制，另外的引导RNA可以通过单独的载体递送。在实施方案中，HNA编码Cas9蛋白或其等同物。

在实施方案中，HNA包含编码蛋白质的转基因，其可以在受试者的细胞中表达以治疗由天然蛋白质的活性降低或消除引起的疾病或病症。因此，在实施方案中，转基因可编码选自下列的蛋白：囊性纤维化跨膜传导调节蛋白(CFTR)、N-乙酰基-α-氨基葡糖苷酶(NAGLU)、N-磺基葡糖胺磺基水解酶(SGSH)、棕榈酰-蛋白硫酯酶1(PPT1)、运动神经元生存蛋白1、端粒(SMN1)、碱性磷酸酶、生物矿化相关蛋白(ALPL，也称为TNALP)、神经胶质细胞源性神经营养因子(GDNF)、葡糖神经酰胺酶β(GBA1)、艾杜糖苷酸酶α-L-(IDUA)、细胞色素P450家族4亚家族V成员2(CYP4V2)、视网膜劈裂蛋白1(RS1)、磷酸二酯酶6B(PDE6B)、甲基-CpG结合蛋白2(MeCP2)、视紫红质(Rho)或蜡样质脂褐质沉积症神经元蛋白1(CLN1)。

在实施方案中，转基因编码CFTR。在实施方案中，CFTR包含CFTR的突变序列、密码子优化序列和/或截短序列。示例性的合适CFTR序列公开于美国专利公开号20110035819，其以引用方式整体并入本文中。在实施方案中，CFTR包含氨基酸708-759(“CFTRΔR”)的缺失。参见Ostedgaard等，Proc.Nat’l Acad.Sci.USA(2005年2月22日)102:2952-2957，其以引用方式整体并入本文中。

在实施方案中，转基因包含、基本上由或由具有SEQ ID NO:4(密码子优化的CFTΔR)或SEQ ID NO:93(全长密码子优化的CFTR)的序列，或与SEQ ID NO:4或93的序列相比具有至多5个、至多10个、至多30个核苷酸变化的序列的核酸组成。在实施方案中，转基因编码的蛋白质包含、基本上由或由具有SEQ ID NO:95(CFTRΔR)或SEQ IS NO 94(全长CFTR)的序列，或具有至多1、2、3、4、5、6、7、8、9或10个不同于SEQ ID NO:94或95的氨基酸的序列的氨基酸组成。

在实施方案中，转基因编码CLN3溶酶体/内体跨膜蛋白、battenin(CLN3)蛋白、α-半乳糖苷酶A(GLA)或酸性α-葡糖苷酶(GAA)。

在实施方案中，GAA蛋白由SEQ ID NO:5、6或7的序列，或与SEQ ID NO:5、6或7相比具有至多5个、至多10个或至多30个核苷酸变化的序列编码。在实施方案中，GAA蛋白包含SEQ ID NO:8的氨基酸序列，或具有至多1、2、3、4、5、6、7、8、9或10个不同于SEQ ID NO:8的氨基酸的序列。

在实施方案中，GLA蛋白由核苷酸序列SEQ ID NO:9或10，或与SEQ ID NO:9或10相比具有至多5个、至多10个或至多30个核苷酸变化的序列编码。在实施方案中，GLA蛋白包含SEQ ID NO:11的氨基酸序列，或具有至多1、2、3、4、5、6、7、8、9或10个不同于SEQ ID NO:11的氨基酸的序列。

在实施方案中，CLN3蛋白由SEQ ID NO:12或13的核苷酸序列，或与SEQ ID NO:12或13相比具有至多5个、至多10个或至多30个核苷酸变化的序列编码。在实施方案中，CLN3蛋白包含SEQ ID NO:14的氨基酸序列，或具有至多1、2、3、4、5、6、7、8、9或10个不同于SEQID NO:14的氨基酸的序列。

在实施方案中，转基因包含由表4中列出的核酸序列中的任一个，或与由表4中列出的DNA序列中的任一个相比具有至多5个、至多10个或至多30个核苷酸变化的序列。在实施方案中，转基因编码表4中列出的氨基酸序列中的任何一个，或具有至多1、2、3、4、5、6、7、8、9或10个不同于表4中列出的氨基酸序列中的任何一个的氨基酸的序列。

表4

在实施方案中，转基因包含SEQ ID No:99-133中的任一个所示的核酸序列，或与SEQ ID No:99-133中的任一个相比具有至多5个、至多10个或至多30个核苷酸变化的序列。在实施方案中，转基因包含SEQ ID No:134-151中的任一个所示的氨基酸序列，或具有至多1、2、3、4、5、6、7、8、9或10个不同于SEQ ID No:134-151中的任一个的氨基酸的序列。

在实施方案中，异源核酸编码报告蛋白；例如荧光蛋白。

制备AAV病毒载体的方法

多种方法可用于制备AAV病毒载体。在实施方案中，通过使用辅助病毒或辅助质粒和细胞系实现包装。辅助病毒或辅助质粒含有促进病毒载体产生的元件和序列。在另一个方面，辅助质粒被稳定地整合到包装细胞系的基因组中，使得包装细胞系不需要用辅助质粒进行额外的转染。

在实施方案中，细胞是包装细胞系或辅助细胞系。在方面的实施方案中，辅助细胞系是真核细胞；例如，HEK 293细胞或293T细胞。在实施方案中，辅助细胞是酵母细胞或昆虫细胞。

在实施方案中，细胞包含编码四环素激活蛋白的核酸；和调节四环素激活蛋白表达的启动子。在实施方案中，调节四环素激活蛋白表达的启动子是组成型启动子。在实施方案中，启动子是磷酸甘油酸激酶启动子(PGK)或CMV启动子。

辅助质粒可以包含，例如，至少一种病毒辅助DNA序列，其衍生自编码包装复制失能的AAV所需的反式全病毒粒子蛋白的复制失能的病毒基因组，和用于产生能够以高滴度包装复制失能的AAV而不产生复制失能的AAV的病毒粒子蛋白。

用于包装AAV的辅助质粒是本领域已知的，参见例如美国专利公开号2004/0235174A1，其以引用的方式并入本文中。如文中所述，作为非限制性实例，AAV辅助质粒可含有由各自的原始启动子或异源启动子控制的Ad5基因E2A、E4和VA作为辅助病毒DNA序列。AAV辅助质粒可另外含有表达盒，用于表达标记蛋白如荧光蛋白，以允许容易地单检测所需靶细胞的转染。

本公开提供了产生AAV颗粒的方法，包括用本文公开的AAV辅助质粒中的任一种；以及本文公开的AAV载体中的任一种来转染包装细胞系。在实施方案中，AAV辅助质粒和AAV载体共转染到包装细胞系中。在实施方案中，细胞系是哺乳动物细胞系，例如人胚肾(HEK)293细胞系。本公开提供了包含本文公开的AAV载体和/或AAV颗粒中的任一种的细胞。

药物组合物

本公开提供了包含本文所述AAV载体、AAV衣壳和/或AAV颗粒中的任一种的药物组合物。通常，施用AAV颗粒以用于疗法。

如本文所述，药物组合物可通过药理学领域已知或开发的任何方法配制，所述方法包括但不限于使活性成分(例如病毒颗粒或重组载体)与赋形剂或其它辅助成分接触，将产物划分或包装为剂量单位。本公开的病毒颗粒可以配制为具有期望的特征，例如增加的稳定性、增加的细胞转染、持续或延迟的释放、生物分布或向性、体内编码蛋白的调节或增强的翻译、以及体内编码蛋白的释放特征谱。

因此，药物组合物可以进一步包含盐水、类脂质、脂质体、脂质纳米粒子、聚合物、脂质复合物、核-壳纳米粒子、肽、蛋白质、用病毒载体转染的细胞(例如，用于移植到受试者中)、纳米粒子模拟物或其组合。在实施方案中，药物组合物被配制为纳米粒子。在实施方案中，纳米粒子是自组装的核酸纳米粒子。

根据本公开的药物组合物可以以单一单位剂量和/或以多个单一单位剂量制备、包装和/或散装销售。活性成分的量通常等于将被施用给受试者的活性成分的剂量和/或这样的剂量的合宜比率，例如这样的剂量的一半或三分之一。本发明的制剂可以包括一种或多种赋形剂，各赋形剂的量一起增加病毒载体的稳定性，增加细胞转染或病毒载体转导，增加病毒载体编码的蛋白质的表达，和/或改变病毒载体编码的蛋白质的释放特征谱。在实施方案中，药物组合物包含赋形剂。赋形剂的非限制性实例包括溶剂、分散介质、稀释剂或其它液体媒介物、分散或悬浮助剂、表面活性剂、等渗剂、增稠剂或乳化剂、防腐剂或其组合。

在实施方案中，药物组合物包含冷冻保护剂。术语“冷冻保护剂”是指能够在冷冻期间减少或消除对物质的损害的试剂。冷冻保护剂的非限制性实例包括蔗糖、海藻糖、乳糖、甘油、右旋糖、棉子糖和/或甘露醇。

治疗方法

本公开提供了预防或治疗病症的方法，包括向受试者施用治疗有效量的本文公开的任一种药物组合物，基本上由其组成或由其组成。

在实施方案中，所述病症是CNS病症、皮肤病症、肺病症、肌肉病症、肺病症或眼科疾病(或视网膜疾病)。在实施方案中，所述病症是囊性纤维化。

在实施方案中，所述病症是低磷酸酯酶症、肌萎缩性侧索硬化(ALS)、脊髓性肌萎缩(SMA)、隐性营养不良性大疱性表皮松解症(RDEB)、溶酶体贮积症(包括杜兴氏肌营养不良和贝克肌营养不良)、青少年巴特氏病(Batten disease)、小儿巴特氏病、常染色体显性病症、肌营养不良、Bietti晶状体营养不良、视网膜劈裂症(例如变性、遗传、牵拉、渗出性)、血友病A、血友病B、多发性硬化、糖尿病、法布里病(Fabry disease)、庞皮病(Pompedisease)、神经元蜡样质脂褐质沉积症1(CLN1)、CLN3病(或青少年神经元蜡样质脂褐质沉积症)、戈谢病、癌症、关节炎、肌肉消瘦、心脏病、内膜增生、Rett综合征、癫痫、亨延顿氏舞蹈病(Huntington's disease)、阿尔茨海默病、自身免疫性疾病、囊性纤维化、地中海贫血、赫尔勒氏综合征(MPS IH)、Sly综合征、沙伊综合征(Scheie Syndrome)、胡-射二氏综合征(Hurler-Scheie Syndrome)、亨特综合征、Sanfilippo综合征A(粘多糖贮积病IIIA或MPSIIIA)、Sanfilippo综合征B(粘多糖贮积病IIIB或MPS IIIB)、Sanfilippo综合征C、Sanfilippo综合征D、莫基奥综合征(Morquio Syndrome)、马-兰二氏综合征(Maroteaux-Lamy Syndrome)、克腊比氏病(Krabbe's disease)、苯丙酮尿症、脊髓小脑性共济失调、LDL受体缺乏、高血氨症、贫血、关节炎或腺苷脱氨酶缺乏。

除了本文公开的特定转基因之外，已知的活性酶序列可以用作转基因以递送功能性酶活性。

治疗囊性纤维化的挑战之一是在病毒颗粒中包装CFTR基因时的大小限制和病毒颗粒向肺细胞递送的困难。本公开的AAV颗粒通过提供有效包装并具有更好的肺向性的CFTR转基因构建体解决了这些问题。因此，在实施方案中，本公开提供了用于治疗囊性纤维化的组合物和方法。

在实施方案中，所述病症是CLN3疾病。CLN3疾病或幼年神经元蜡样质脂褐质沉积症是由CLN3基因中常染色体隐性遗传突变引起的溶酶体贮积病。CLN3疾病是进行性神经变性疾病，其中中枢神经系统(CNS)受到极大影响，导致行为问题、视力丧失和其它认知障碍。

在实施方案中，所述病症是法布里病。法布里病是由α-半乳糖苷酶A(GLA)活性缺乏引起的X-连锁溶酶体贮积症，所述α-半乳糖苷酶A(GLA)活性缺乏导致溶酶体中糖脂产物、球形三酰神经酰胺(Gb3)和溶血Gb3的积累。疾病表现是高度异质性的，但通常包括外周神经营养性疼痛的频繁发作、血管角化病、减少的汗液产生、角膜营养不良和胃肠道并发症。随着疾病的发展，患者患有心肌病、肾功能不全和脑血管疾病，所有这些疾病都是法布里病患者寿命缩短的主要原因。尽管男性是受GLA基因突变影响最严重的患者群体，但越来越清楚女性患者也经常出现症状，但经常被误诊。酶替代疗法(ERT)是目前唯一FDA批准的治疗法布里病的疗法，需要每周两次注射相对大量的重组蛋白。虽然ERT可减少Gb3在心脏、肾脏和脉管系统中的累积，但其无法完全治疗法布里病(Fabry)的所有症状，主要是因为其无法有效进入CNS。基因疗法策略已经被研究，虽然许多策略在纠正糖脂累积方面显示出巨大的前景，但是大多数都未能有效地进入CNS，并且还遭受在GLA替代期间经常看到的免疫应答。

在实施方案中，本文公开的AAV病毒载体用于治疗对ERT无反应或ERT未能解决所有症状的患者的法布里病。在实施方案中，本文公开的AAV病毒载体用于治疗已施用ERT的患者的法布里病。

在实施方案中，所述病症是庞皮病。庞皮病是由酸性α-葡糖苷酶(GAA)活性缺乏导致糖原在溶酶体中积累所引起的溶酶体贮积症。该疾病表现为肌营养不良症的形式，其主要影响平滑肌和横纹肌以及中枢神经系统(CNS)，具有早期死亡率。酶替代疗法(ERT)是目前唯一FDA批准的治疗庞皮病的疗法，需要每周两次注射相对大量的重组蛋白。虽然ERT能显著降低未治疗而典型地死于两岁的幼儿庞皮症患者的死亡率，但它不能完全改善庞皮症的所有症状，主要是由于其不能有效进入CNS并导致对GAA蛋白的免疫应答。基因疗法策略已经被研究，并且尽管许多在纠正庞皮病的糖原积累和其它症状方面显显示出很大的前景。大多数患者在GAA替代期间经历了严重的免疫应答。以前的工作已经证明肝特异性表达可以使动物耐受GAA蛋白并显著降低体液应答。

在实施方案中，本文公开的AAV病毒载体用于治疗已施用ERT的患者的庞皮病；例如对ERT无反应的患者，或ERT不能治疗所有症状的患者。

在实施方案中，癌症是实体癌；例如膀胱、乳腺、宫颈、结肠、直肠、子宫内膜、肾、唇、口、肝、黑素瘤、间皮瘤、非小细胞肺、非黑素瘤皮肤、卵巢、胰腺、前列腺、肉瘤、小细胞肺肿瘤或甲状腺。

在实施方案中，所述病症是眼科疾病。眼睛是免疫豁免组织。只有非常少量的病毒是治疗益处所必需的。在实施方案中，眼科疾病影响感光细胞和RPE细胞。在一些实施方案中，所述眼科疾病包括、基本上由或由下列各项组成：色素性视网膜炎(例如，常染色体隐性(SPATA7基因；LRAT基因；TULP1基因)、常染色体显性(AIPL1基因)和X连锁(RPGR基因))、与斑萎蛋白(bestrophin)-1(BEST-1)基因中的突变相关的眼病(例如，卵黄状黄斑营养不良、年龄相关性黄斑变性、常染色体显性玻璃体视网膜脉络膜病、青光眼、白内障)、Leber先天性黑朦(LCA；芳基-烃互作用蛋白样1(AIPL1)基因)、视锥-视杆营养不良(CRD；ABCA4基因)、斯特格式病(Stargardt's)(ABCA4基因)、无脉络膜(CHM基因)、乌谢尔综合征(UsherSyndrome)(MYO7A基因；CDH23基因；USH2A基因；CLRN1基因)、视网膜劈裂症(RS1基因)、Bietti晶状体营养不良(CYP4V2基因)或全色盲(CNGA3基因、CNGB3基因、GNAT2基因、PDE6C基因或PDE6H基因)。组成。

在实施方案中，所述受试者是哺乳动物；例如人。在特定方面，所述人是婴儿；例如，3岁以下、2岁以下或1岁以下。

本文公开的治疗和预防方法可以与适当的诊断技术组合以鉴定和选择用于疗法或预防的患者。例如，本文公开的治疗或预防病症例如囊性纤维化的方法还可以包括进行遗传测试以鉴定与受试者中的病症相关的基因突变或缺失的步骤。在实施方案中，治疗或预防病症例如囊性纤维化的方法包括向先前已被鉴定为携带与所述病症相关的突变或处于发生所述病症的高风险(例如基于遗传因素)的受试者施用。

本公开提供了增加宿主细胞中的蛋白质水平的方法，所述方法包括使所述宿主细胞与本文公开的AAV颗粒中的任一种接触，其中所述AAV颗粒包含本文公开的AAV载体中的任一种，所述AAV载体包含编码所述蛋白的HNA序列。在实施方案中，蛋白质是治疗性蛋白质。在实施方案中，宿主细胞是体外、体内或离体的。在实施方案中，宿主细胞来源于受试者。在实施方案中，受试者患有病症，与正常受试者中蛋白质的水平和/或功能相比，所述病症导致蛋白质的水平和/或功能降低。

在实施方案中，蛋白质的水平在宿主细胞中被提高到约1×10^-7ng、约3×10^-7ng、约5×10^-7ng、约7×10^-7ng、约9×10^-7ng、约1×10^-6ng、约2×10^-6ng、约3×10^-6ng、约4×10^- ⁶ng、约6×10^-6ng、约7×10^-6ng、约8×10^-6ng、约9×10^-6ng、约10×10^-6ng、约12×10^-6ng、约14×10^-6ng、约16×10^-6ng、约18×10^-6ng、约20×10^-6ng、约25×10^-6ng、约30×10^-6ng、约35×10^-6ng、约40×10^-6ng、约45×10^-6ng、约50×10^-6ng、约55×10^-6ng、约60×10^-6ng、约65×10^-6ng、约70×10^-6ng、约75×10^-6ng、约80×10^-6ng、约85×10^-6ng、约90×10^-6ng、约95×10^- ⁶ng、约10×10^-5ng、约20×10^-5ng、约30×10^-5ng、约40×10^-5ng、约50×10^-5ng、约60×10^- ⁵ng、约70×10^-5ng、约80×10^-5ng或约90×10^-5ng的水平。

本公开提供了将目标基因导入受试者细胞的方法，包括使细胞与有效量的本文公开的任一种AAV病毒载体颗粒接触，其中所述颗粒含有本文公开的任一种包含目标基因的AAV载体。

剂量和施用

确定最有效的施用方式和剂量的方法是本领域技术人员已知的，并且将随用于治疗的组合物、治疗的目的和被治疗的受试者而变化。可以进行单次或多次施用，剂量水平和模式由治疗医师选择。注意到剂量可能受施用途径的影响。合适的剂量制剂和施用所述试剂的方法是本领域已知的。这种合适剂量的非限制性实例可以是每次施用低至10⁹个载体基因组至至多10¹⁷个载体基因组。

在本文所述方法的实施方案中，施用给受试者的病毒颗粒(例如AAV)的数量范围为约10⁹个至约10¹⁷个。在特定的一些实施方案中，给受试者施用约10¹⁰至约10¹²、约10¹¹至约10¹³、约10¹¹至约10¹²、约10¹¹至约10¹⁴、约5×l0¹¹至约5×10¹²或约10¹²至约10¹³个病毒颗粒。对于向人眼的施用，可以使用约1×10¹⁰vg/眼的总剂量，并且可以将5×10⁹vg/眼的总剂量用于小鼠的眼。非侵入性体内成像技术可用于监测动物的功效/安全性，其包括但不限于扫描激光检眼镜检查(SLO)、光学相干断层扫描(OCT)、多光子显微术、荧光素血管造影术。

在实施方案中，AAV颗粒修复受试者的基因缺陷。在实施方案中，在成功治疗的细胞、组织、器官或受试者中修复的靶多核苷酸或多肽与未修复的靶多核苷酸或多肽的比率为至少约1.5:1、约2:1、约3:1、约4:1、约5:1、约6:1、约7:1、约8:1、约9:1、约10:1、约20:1、约50:1、约100:1、约1000:1、约10,000:1、约100,000:1或约1,000,000:1。修复的靶多核苷酸或多肽的量或比率可以通过本领域已知的任何方法来确定，包括但不限于Western印迹、Northern印迹、Southern印迹、PCR、测序、质谱、流式细胞术、免疫组织化学、免疫荧光、荧光原位杂交、下一代测序、免疫印迹和ELISA。

在实施方案中，通过静脉内、鞘内、脑内、心室内、鼻内、气管内、耳内、眼内或眼周、口服、直肠、透粘膜、吸入、经皮、肠胃外、皮下、皮内、肌内、胸膜内、局部、淋巴内、脑池内将病毒颗粒引入受试者；这样的引入也可以是动脉内、心脏内、心室下、硬膜外、大脑内、脑室内、视网膜下、玻璃体内、关节内、腹膜内、子宫内或其任何组合。在实施方案中，作为非限制性实例，将病毒颗粒递送至所需靶组织，例如肺、眼或CNS。在实施方案中，病毒颗粒的递送是全身性的。脑池内施用途径包括将药物直接施用至脑室的脑脊液中。其可以通过直接注射到大池中或通过永久定位的管来执行。

为了眼内治疗眼科疾病(或眼病症)，存在本领域技术人员已知的多种施用模式，包括但不限于：泪腺(LG)施用、局部滴眼剂、角膜基质内施用、前房内施用(前房)、玻璃体内施用、视网膜下施用、全身施用或其组合。80％的遗传性眼病发生在感光细胞中。小容量基因疗法的玻璃体内递送可在门诊部进行。

本公开的AAV载体、AAV颗粒或组合物的施用可以在整个治疗过程中以一个剂量、连续或间歇地实现。在实施方案中，本公开的AAV载体、AAV颗粒或组合物通过注射、输注或植入进行肠胃外施用。

在实施方案中，本公开的AAV颗粒显示出增强的脑和颈椎向性。在实施方案中，本公开的病毒颗粒可以穿过血脑屏障(BBB)。在实施方案中，本公开的AAV颗粒通过视网膜下和玻璃体内注射表现出高视网膜向性。在实施方案中，本公开的AAV颗粒靶向多种类型的眼细胞，例如视锥细胞、视杆细胞和视网膜色素上皮细胞(RPE)。在实施方案中，本公开的AAV颗粒逃脱针对天然血清型的中和抗体，并因此能够实现潜在的重新给药。在另一方面，本公开的AAV颗粒和组合物可与用于治疗的病症的其它已知治疗组合施用。

试剂盒

在实施方案中，本文所述的试剂、载体或组合物可以组装成药物或诊断或研究试剂盒以促进它们在治疗、诊断或研究应用中的使用。在实施方案中，本公开的试剂盒包括本文所述的修饰的AAV衣壳蛋白、AAV载体、AAV颗粒、宿主细胞、分离的组织、组合物或药物组合物中的任一种。

在实施方案中，试剂盒还包括使用说明书。具体地，这样的试剂盒可以包括一种或多种本文所述的试剂，以及描述这些试剂的预期应用和正确使用的说明书。作为一个实例，在实施方案中，试剂盒可以包括关于混合试剂盒的一种或多种组分和/或分离和混合样品并施用于受试者的说明书。在实施方案中，试剂盒中的试剂是适合于特定应用和试剂的施用方法的药物制剂和剂量。用于研究目的试剂盒可以含有用于进行各种实验的适当浓度或量的组分。

试剂盒可以设计成便于使用本文所述的方法，并且可以采取许多形式。在适用的情况下，试剂盒的每种组合物可以以液体形式(例如，在溶液中)或以固体形式(例如，干粉)提供。在某些情况下，一些组合物可以是可构成的或另外可加工的(例如，加工成活性形式)，例如，通过添加合适的溶剂或其它物质(例如，水或细胞培养基)，其可以或可以不与试剂盒一起提供。在实施方案中，组合物可以在保存溶液(例如，冷冻保存溶液)中提供。保存溶液的非限制性实例包括DMSO、多聚甲醛和

(Stem Cell Technologies,Vancouver,Canada)。在实施方案中，保存溶液含有一定量的金属蛋白酶抑制剂。

在实施方案中，试剂盒在一个或多个容器中含有本文所述的任何一种或多种组分。因此，在实施方案中，试剂盒可以包括容纳本文所述的试剂的容器。所述试剂可以是液体、凝胶或固体(粉末)的形式。所述试剂可以无菌制备，包装在注射器中并冷冻运输。或者，它们可以容纳在小瓶或其它容器中以便储存。第二容器可以具有无菌制备的其它试剂。或者，试剂盒可以包括预混合的活性剂，并在注射器、小瓶、管或其它容器中运输。试剂盒可以具有将试剂施用于受试者所需的一种或多种或所有组分，例如注射器、局部施用装置或IV针管和袋。

应当理解，虽然已经结合上述实施方案描述了本发明，但是上述描述和示例旨在说明而不是限制本发明的范围。本发明范围内的其它方面、优点和修改对于本发明所属领域的技术人员将是显而易见的。

另外，在本发明的特征或方面以马库什组的形式描述的情况下，本领域技术人员将认识到本发明也因此以马库什组的任何单独成员或成员的亚组的形式描述。

实施例

实施例1

衣壳生成平台

使用图1所示的AAV衣壳生成平台生成本文提供的一些AAV衣壳序列(例如AAV204、AAV110)。简言之，该平台包括脱氧核糖核酸酶I片段化步骤，以及组装和扩增步骤，其最终导致嵌合衣壳文库的形成。本文提供的其它AAV衣壳序列(例如AAV214)通过合理设计产生。

通过与已知AAV衣壳蛋白的氨基酸序列比对来分析使用这些方法产生的衣壳蛋白。来自AAV204(SEQ ID NO:2)和AAV6(SEQ ID NO:63)的VP1蛋白序列的序列比对示出于图20中。AAV 214、AAV 214A、AAV 214e、AAV 214e8、AAV 214e9、AAV 214e10、AAV 214AB和AAVITB102_45的VP1氨基酸序列的序列比对在图21中提供。AAV 214、AAV 214A、AAV 214e、AAV214e8、AAV 214e9、AAV 214e10、AAV 214AB和AAV ITB102_45的VP2氨基酸序列的序列比对在图22中提供。AAV 214、AAV 214A、AAV 214e、AAV 214e8、AAV 214e9、AAV 214e10、AAV214AB和AAV ITB102_45的VP1氨基酸序列的序列比对在图23中提供。

病毒载体可以使用本领域已知的标准三重转染方法制备。简言之，将分别表达病毒衣壳蛋白、辅助蛋白(例如必需病毒Rep和Cap蛋白)和目的转基因的三个分开的质粒转染到贴壁或悬浮293细胞中，随后使用超速离心或层析，接着渗滤/超滤和末端无菌过滤收获病毒颗粒。参见，例如，Guo等，Mol.Ther.Methods Clin.Dev.第13卷第40-46页中的第44页(2018年11月)；Wang等，Human Gene Ther.Methods,第25卷第261-68页中的第262页；以及Gao等，Human Gene Ther.Methods,第11卷第2079-91页，其中每篇文献都以引用方式整体并入本文中以用于所有目的。

实施例2

AAV214和AAV204病毒载体的表征

如下所述评估AAV214或AAV204载体在不同靶组织中的转导效率。

体外评价了包含EGFP转基因的AAV214病毒载体(AAV214-GFP)和包含EGFP转基因的AAV9病毒载体(AAV9-GFP)的转导效率。HEK 293细胞以50,000个细胞/孔接种于96孔板中。用5E+5MOI的AAV214-GFP或AAV9-GFP转导细胞。转导后45小时拍摄的图像示出，在HEK293细胞中AAV214-GFP的转导效率更高(图2A)。注意到，除非另有说明，本文所用的“GFP”是指EGFP(参见，例如Zhang等(1996)Biochem.Biophys.Res.Commc’n.227(3):707-11)。

为了测试体内转导效率，通过静脉内(IV)注射在200μL TMN200(200mM Tris-HCl、1mM MgCl2、200mM NaCl和0.001％Pluronic F68)中的2E+11vg AAV214-GFP或AAV9-GFP对10周龄的C57BL/6小鼠给药。十三天后，将小鼠安乐死，收集内脏(脑、脊髓(颈和腰)、坐骨神经、眼、心、肾、肝、肺、睾丸、脾和肌肉)的组织样品，分离总DNA并使用绝对qPCR方法分析GFP基因拷贝数估计。使用Prism软件(GraphPad软件)对获得的AAV生物分布数据作图，进行统计分析。在大多数测试组织中，对对数变换数据进行的非配对t-检验未显示AAV9-GFP和AAV214-GFP转导效率之间的统计学显著差异(p＜0.05)。然而，在坐骨神经和肌肉的情况下，从给予AAV214-GFP的动物分离的每微克总DNA中检测到的病毒DNA拷贝数的平均值较高，并且在统计学上显著不同于给予AAV9-GFP的动物(坐骨神经：4.1倍，p＝0.0228；肌肉：3倍，p＝0.0125)(图2B)。

将脑样品分成两半重复相同的实验。一半用于总DNA分离，随后使用绝对qPCR进行生物分布分析。另一半用于总RNA分离、脱氧核糖核酸酶处理、转化为cDNA和qPCR分析以定量EGFP基因表达水平。使用Prism软件对获得的AAV生物分布和转基因表达数据作图，进行统计分析。对对数变换数据进行的非配对t-检验未显示脑组织中AAV9-GFP和AAV214-GFP转导效率(p＝0.7668)或表达水平(p＝0.0709)之间的统计学显著差异(图2C)。

通过视网膜下(右眼)和玻璃体内(左眼)注射，给野生型C57BL/6J小鼠施用一组AAV病毒载体，包括AAV204-GFP、AAV110-GFP和AAV214-GFP。对于两种施用方法，注射1μL 5E+12vg/mL(5E+9vg/眼)的AAV载体，10天后用HRA2 Spectralis扫描激光检眼镜(HeidelbergEngineering,Carlsbad,CA)对动物成像。从分析中省略了白内障妨碍充分观察的图像。检眼镜检查成像显示，如果给予到视网膜下腔内，所有测试的病毒都能够转染视网膜细胞。然而，仅AAV204和AAV110显示出通过玻璃体内递送介导的视网膜细胞的增强的转导(图3A)。玻璃体内给予AAV204-GFP的小鼠眼睛的免疫组织化学分析证实GFP在各种类型的视网膜细胞中表达，所述视网膜细胞包括感光细胞、RPE、Müller胶质细胞、视网膜神经节细胞和双极细胞(图3B)。

将AAV204-GFP和AAV9-GFP鞘内注射(1E+13vg)和/或玻璃体内注射(1.5E+12vg)给予2.5-3岁的食蟹猴(Macaca fascicularis)，每只体重约2kg。四周后，将动物安乐死，通过RT-qPCR评价GFP表达。数据分析表明AAV204-GFP介导的递送导致在大多数被分析的组织中增强的GFP表达，包括脑和脊髓的特定区域。参见图4。玻璃体内给予(每只眼1.5E+12vgAAV204-GFP)的食蟹猴的眼睛通过扫描激光检眼镜检查(SLO)进行评价，切片并使用常规免疫化学染色方法分析GFP、视紫红质和基因组DNA。如图5A和5B所示，AAV204-GFP的施用导致载体在眼睛的周边视网膜和中央凹区域中的显著转导。在视网膜细胞包括感光细胞、RPE、双极细胞和神经节细胞中观察到AAV204递送的GFP表达增强(图5B)。大量的视杆细胞和视锥细胞被转导到黄斑中(图5C)。

AAV204载体也可与RPE特异性启动子组合以特异性表达蛋白质。图5D-5F示出由VMD2(卵黄状黄斑变性-2)启动子(SEQ ID NO159)驱动的来自AAV204的GFP表达。玻璃体内施用2.5×10¹²个病毒基因组(vg)载体，并在14天和28天(处死)监测表达。在第14天(图5D)和第28天(图5E)进行扫描激光检眼镜(SLO)成像。图5F示出第28天时外周的GFP表达和核(DAPI)。

还在非人灵长类动物外植体培养物中评价AAV204-GFP。在人道安乐死的动物的1小时内从眼睛分离食蟹猴视网膜。将视网膜解剖成～5×5mm切片，并在Transwell插入培养皿中培养。分离后一天，用培养基中的AAV204-GFP转导外植体，并在转导后温育一周。固定外植体，包埋并切片用于标准免疫组织化学。切片用GFP(绿色)和视紫红质(红色)染色，并用荧光显微镜成像。在AAV204-GFP转导后，切片在感光细胞层中显示出显著的GFP表达(图6)。

使用中和抗体测定法评价AAV204载体的免疫原性(图7)。将包含AAV9衣壳和萤火虫萤光素酶表达盒的AAV9-Luc病毒或包含AAV204衣壳和萤火虫萤光素酶表达盒的AAV204-Luc病毒与来自AAV9处理的人受试者(处理后60天)的各种血清稀释液在MOI为25,000下温育。温育后，将病毒/血清混合物转移至含有20,000个Lec2细胞的孔中。将血清处理的细胞温育24小时，然后测量发射的发光，并与来自以相同MOI用未处理病毒转导的细胞的对照值进行比较。结果表明，AAV204载体颗粒与AAV9载体颗粒相比具有降低的免疫原性(参见图8)。

实施例3

使用由AAV204病毒载体递送的CFTR转基因改善由囊性纤维化跨膜传导调节蛋白(CFTR)基因中的突变引起的缺陷

使用从5’到3’具有5’ITR、小鼠U1A启动子(SEQ ID NO:96)、CFTRΔR转基因、合成poly-A序列(49bp)和3’ITR的pA-CF3质粒(SEQ ID NO:89)制备含有编码密码子优化的CFTR转基因(即，包含SEQ ID NO:4中所示的核酸序列并且编码蛋白质的CFTRΔR基因缺乏全长CFTR的氨基酸708-759)的核酸的AAV204载体颗粒。如下所述，将得到的颗粒用于将CFTRΔR转基因传递到细胞或小鼠中。

体外测定:使用包含CFTRΔR转基因的AAV204病毒载体转导Lec2细胞。FLIPR测定用于测量由AAV204-ΔR病毒载体递送的CFTRΔR转基因的功能性。结果表明，与用缺乏转基因的对照AAV204病毒载体转染的细胞相比，当使用AAV204-CFTRΔR病毒载体转导细胞时，通过用毛喉素(CFTR氯化物通道的已知开放子)刺激，人CFTR(hCFTR)离子通道功能得以恢复。此外，与对照相比，使用AAV204-CFTRΔR病毒载体转导的细胞中的氯离子特异性电流信号与基线相比增加3.5倍。参见图10A，左图。与CFTR选择性抑制剂CFTRinh-172(4-[[4-氧代-2-硫代-3-[3-三氟甲基)苯基]-5-噻唑烷亚基]甲基]苯甲酸)(Tocris Bioscience)(通过http://tocris.com/products/cftrinh-172_3430获得)预温育阻止了CFTRΔR存在时毛喉素诱导的膜电位变化。参见图10B。这些结果证明CFTRΔR表达盒的功能性。

进行膜电位分析以评价CFTRΔR表达盒的功能性是否依赖于用于转染的AAV204-CFTRΔR病毒的量。参见图10B。结果表明在CFTRΔR存在下膜电位的变化确实依赖于递送转基因的病毒颗粒的剂量。我们还使用AAV204表达全长CFTR并获得响应于毛喉素的增加的荧光。(图10C)。我们还通过western印迹证实了AAV204的表达导致全长CFTR和CFTRΔR的完全加工(数据未示出)。这些数据证实AAV204递送任一蛋白都恢复体外氯离子通道功能。

使用小鼠模型的体内测定：气管内给予小鼠包含萤光素酶转基因的AAV204病毒载体。生物发光成像(BLI)用于评估AAV204病毒载体转导肺细胞的能力，如荧光素酶表达所反映，与AAV6相比。图9，上图，示出AAV204病毒载体介导的萤光素酶表达比AAV6病毒载体高约3.5倍。图9下图示出离体BLI示出的左肺和右肺中的表达，在肝或肾中很少或没有表达。这些结果证明AAV204病毒载体能够促进报告转基因在小鼠特定组织中增强的表达。

在称为“F508del”的囊性纤维化小鼠模型中测试包含CFTRΔR转基因的AAV204载体颗粒的效力。这些小鼠携带突变CFTR基因，其包含单个氨基酸F508的缺失，这是在人中最常见的CFTR突变，影响大约90％的CF患者(参见，例如Park等，PLoS One(Feb.10,2016)11(2):e0149131)。将包含CFTRΔR转基因或萤光素酶转基因的AAV204载体颗粒鼻内施用给野生型和F508del小鼠。测定鼻电位差(NPD)以确定CFTRΔR转基因的功能。如图12A所示，与施用含有荧光素酶转基因的对照载体(AAV204-Luc)的小鼠相比，施用AAV204-CFTR载体颗粒的小鼠显示出校正的毛喉素刺激电流。

使用人患者细胞的测定：评价了包含CFTRΔR转基因的AAV204载体颗粒介导hCFTR递送到分离自囊性纤维化患者的人气道细胞中，以及校正这些细胞中氯离子转运的能力。当将包含GFP转基因的AAV204载体颗粒应用于顶端和基底外侧区室时，AAV204转导从囊性纤维化患者分离的人鼻和支气管上皮(HNE和HBE)细胞，并维持在气-液界面培养物中。参见图11A。CFTRΔR蛋白在这些细胞中是膜定位的；参见图11B，左图。图11B，右图示出阐明膜定位的western印迹。

如下所述评价包含CFTRΔR转基因的AAV204载体颗粒的功能性。结果表明，转导包含CFTRΔR转基因的AAV204载体后，CFTR电流在来自囊性纤维化患者的人鼻上皮细胞的外植体培养物中恢复。参见图11C。还通过使用本领域技术人员已知的测量离子在极化上皮表面之间运动的Using室测量跨膜电导的变化，测试AAV颗粒是否能恢复从人囊性纤维化患者分离的鼻和支气管细胞中的CFTR功能。简言之，在Using室中，上皮的顶面和基底外侧表面面向两个含有对称盐溶液的分开的室。离子穿过上皮的转运在两个室之间产生电位差。通过施加穿过上皮的短路电流(I_sc)主动地抵消原本会产生电位差的扩散力。这使得离子在刺激后通过主动转运而移动，如本领域所熟知的，通过该电流的变化(ΔI_sc)和囊性纤维化跨膜电导的计算来测量。参见，例如Li等，J.Cystic Fibrosis(2004年7月)3:123-126；Park等，PLoS One(2016年2月10日)11(2):e0149131。如图12B所示，当转导CFTRΔR时，与载体相比，毛喉素刺激的CFTRinh-172抑制电流恢复到6-7μA/cm²。

总之，我们的结果表明AAV204介导高效递送高表达的功能性CFTR，并且进一步在体外细胞、小鼠模型和人类患者细胞的外植体培养物中恢复CFTR功能。这些结果证明了包含CFTRΔR转基因的AAV204颗粒在囊性纤维化中的治疗潜力。

实施例4：

使用由AAV214载体递送的优化的CLN3转基因改善CLN3疾病引起的缺陷

开发了全身施用后对CNS组织具有增强的向性的AAV衣壳(AAV214)和用于改善CNS和体细胞组织中的生物分布和表达的优化的CLN3(包含SEQ ID NO:122的核酸序列)转基因盒，并测试了其功能性。使用AAV9作为基准来评估AAV214的向性和优化的CLN3转基因盒在幼年神经元蜡样质脂褐质沉积症的小鼠模型中的生物分布，所述模型在C57BL/6背景中缺少跨越CLN3(CLN3Δex7/8)的外显子7和8的1.02kb区段。该CLN3缺失发生在约85％的突变CLN3等位基因中，并概括了许多与人类疾病相关的疾病表型，包括运动缺陷、神经胶质活化和溶酶体贮积材料的进行性积累。

表6.CLN3^Δex7/8小鼠模型的研究设计

将各自包含CLN3转基因的AAV9和AAV214病毒载体(分别为AAV9-CLN3和AAV214-CLN3)静脉内施用给野生型小鼠，剂量为2.0×10¹³vg/kg(病毒载体基因组/千克)。参见表6。30天后，人道地处死动物，收集组织用于生物分布分析，其评价载体颗粒向几个不同器官的递送，包括CNS和脊髓的主要区域(颈和腰)。对对数变换数据进行的非配对t-检验未显示AAV214-CLN3和AAV9-CLN3之间在大多数测试组织的生物分布值上有统计学显著性差异(见图13)。然而，使用AAV214-CLN3与AAV9相比，坐骨神经统计学上显著地(p＝0.0001)高(744％)生物分布，而用AAV9-CLN3更好转导脾(p<0.0001)。目前在较长时间内评估表达和剂量反应的研究表明AAV214-CLN3可用于通过全身施用将CLN3表达盒有效递送到CNS组织。

CLN3转基因的表达通过RTqPCR使用从左脑半球分离的总RNA评估。对对数转化数据的单向ANOVA分析显示给予AAV9-CLN3与AAV214-CLN3的动物(p＝0.4489)的平均CLN3表达值无统计学显著差异。然而，两种测试的病毒载体产生比对照更高的CLN3表达水平(p＜0.0001；图14)。

总之，这些结果表明，如果在CLN3疾病的小鼠模型中通过全身施用，包含优化的CLN3表达盒的新AAV214病毒载体在包括CNS的大多数组织中显示出与AAV9相当的向性。这些结果表明，包含本文所述优化的CLN3转基因的AAV214载体可用于预防和治疗CLN3疾病。

实施例5

使用由AAV214载体递送的优化的GLA转基因改善法布里病引起的缺陷

通过IV注射将包含CBh启动子、CBA-MVM杂合内含子、天然GLA转基因序列和TK65poly-A位点的AAV9和AAV214病毒载体施用给野生型C57BL/6小鼠(参见表7)。通过免疫印迹证实血浆样品中预期的转基因GLA蛋白的大小(图15)。在评估血浆、脑、脊髓、心脏、肾、肝和眼中的GLA酶活性。对log转化的GLA酶活性值进行的统计分析表明，所有AAV214-GLA转导样品与对照相比具有统计学上显著更高的GLA活性(p＜0.0001)。与AAV9-GLA相比，在AAV214-GLA转导的血浆、脑和脊髓组织中GLA酶活性也统计学显着更高(图16)。总之，GLA酶活性分析表明AAV214构建体有效转导进入多个靶组织，特别是CNS组织，证明AAV214载体在法布里病患者中的治疗益处。

表7.动物研究设计

在野生型动物中进行10天的研究后，没有观察到通过AAV9或AAV214病毒载体全身施用GLA转基因的急性毒性效应。在本实验中，没有动物显示出任何由于治疗而产生的副作用。全身施用后AAV9和AAV214有效递送至靶组织，特别是递送至CNS、心脏和肾脏证明能安全转导与法布里病相关的关键靶组织。

实施例6

使用由AAV214载体递送的优化GAA转基因改善由Pompe病引起的缺陷

将包含CBh启动子、CBA-MVM杂合内含子、密码子优化的GAA转基因序列和BGHpoly-A位点的AAV9-GAA和AAV214-GAA载体静脉内给予到野生型C57BL/6小鼠中(见表8)。为了确定转基因是否被有效传递到靶组织，在来自治疗小鼠的脑、脊髓、膈膜、二头肌、肝和血浆中测试GAA酶活性蛋白。GAA酶活性的对数转化值的单向ANOVA分析显示，与对照动物相比，给药动物的所有测试组织具有统计学上显著(p＜0.002)更高的GAA活性。除了血浆中AAV9有轻微优势(p＝0.0018)外，给予AAV214和AAV9的组织之间没有显示出酶活性的统计学显著差异(图19A-E)。GAA酶活性的分析证实AAV214构建体有效转导到多个靶组织中，包括穿过血脑屏障的能力，以及转导到对于治疗庞皮病重要的组织，如二头肌和膈膜(图19)。这些结果提示单次静脉内注射包含如本文所述的优化的GAA表达盒的AAV214病毒载体可能足以实现将校正的GAA转基因递送至靶组织。在野生型动物中进行10天研究后，没有观察到GAA转基因通过AAV9或AAV2l4载体全身施用的急性毒性效应。

图19F示出AAV递送的GAA对潜在分子病理学的修复。来自用包装有密码子优化的人GAA的AAV衣壳静脉内处理的GAA-/-小鼠的糖原分析。糖原含量是通过在淀粉葡糖苷酶处理后释放葡萄糖来间接测量的。用无限葡萄糖试剂(Infinity Glucose Reagent)测量游离葡萄糖，并在SpectraMax i3x上分析。数据表示为gaa-/-媒介物对照治疗的动物的％。数据显示由AAV递送的GAA获得的糖原水平的降低。用AAV214在所有靶组织中观察到糖原清除，其表现与AAV9一样有效。

这些数据证实AAV9和AAV214的全身递送，特别是具有肌肉和外周神经系统(PNS)表达的全身递送，证明了安全转导与庞皮病相关的关键靶组织和恢复GAA功能的能力。

表8：动物研究设计

实施例7

AAV110载体颗粒显示出高度特异性的肌肉向性

使用编码AAV110衣壳蛋白的pAAV110质粒(也称为ITCord1.10质粒)制备AAV110颗粒。在C57Bl/6野生型小鼠中，以单次注射将包含CBh启动子、CBA-MVM杂合内含子、EGFP转基因序列和BGH poly-A位点的AAV110-GFP病毒载体施用(总共1×10¹¹vg，相当于5×10¹²vg/kg)到每条腿(股二头肌)。另一组动物施用等量的AAV9-GFP病毒载体用于比较。

通过腿部肌肉荧光成像来评价GFP表达。图24A。数据显示，施用AAV110-GFP病毒载体的右腿和左腿均表达高水平的GFP，从而建立AAV110衣壳的肌肉向性。相比之下，AAV9-GFP载体颗粒提供了显著更少的肌肉表达(图24B)。

为了评估通过肌内给予AAV110-GFP或AAV9-GFP诱导的其它组织中的GFP转基因分布，我们检测了一组器官中的转基因生物分布(BD)。参见图25。数据证实AAV110转导主要发生在肌肉中，以及坐骨神经和脾中。与AAV9相比，AAV110在脑、肾、眼、肺、心、肝和睾丸中显示出极少或没有生物分布。在每种情况下，BD为用AAV9肌内递送转基因获得的BD的约3％或更低。

肌肉组织的免疫组织化学分析证实，用AAV110在肌肉中的GFP表达水平高，而用AAV9的GFP表达水平低(图26)。该数据证实AAV110的优异肌肉向性和表达。

实施例8

AAV214载体颗粒在IM和IV施用后在肌肉中提供高水平的表达

产生包含AAV214衣壳蛋白和由U1a启动子驱动的萤光素酶表达盒(AAV214-Luc)的AAV病毒载体。我们将AAV214-Luc给予至成年野生型大鼠的右腿，剂量为每肌肉5×10¹²vg/kg，总体积为每肌肉0.1mL。左腿未处理。为了测量表达，我们将肌肉暴露于荧光素并测量发射光。下表中的数据显示注射的肌肉而非未治疗的肌肉在施用后28天显示出高表达。图27示出组织中的荧光素酶活性，表明表达的酶的活性。

用CBh启动子驱动的不同的转基因、密码子优化的SMN-1(运动神经元生存蛋白1)(其在脊髓性肌肉萎缩(SMA)中有缺陷)获得了类似的结果。我们比较了静脉内施用的AAV214-SMN1病毒载体颗粒与AAV9-SMN1载体颗粒在静脉内给予时表达SMN-1的能力。图28示出感染幼年野生型小鼠后胫骨前肌组织中SMN1的表达。数据说明，当静脉内递送时，AAV214载体颗粒提供相对于载体至少10％至30％增加的改善的表达，并适于肌肉转导。

比较AAV214和AAV9病毒载体转导肌肉组织显示出IM递送的AAV214能够比AAV9转导更大的肌肉区域。通过IM注射后10天的免疫组织化学来分析大鼠全肌(股二头肌)的GFP或mCherry表达。用GFP和mCherry pAb探测固定和冷冻切片。与AAV9相比，AAV214展示出显著更大的转导区域，其主要局限于与注射位点一致的肌肉的上部。(图26B)。

实施例9

含有源自AAV214的衣壳蛋白的AAV载体颗粒在IV给予后在肌肉中展示高表达

通过用已知AAV血清型(AAV8、AAV9、AAVrh10)的氨基酸序列交换AAV214 VP1蛋白的N-末端来修饰它们，从而产生下表中所示的变体。然后基本上如实施例1所述，用每种新获得的衣壳蛋白制备AAV病毒载体颗粒，并评估它们在静脉内施用后转导肌肉的能力。我们发现每种病毒载体在腿部和心脏中赋予良好的肌肉转导(图29)。对数转化的生物分布数据的单向ANOVA分析没有显示所测试的病毒载体的平均生物分布值的统计学显著差异(p＞0.05)。

VP1氨基酸SEQ ID NO	VP1核酸SEQ ID NO	AAV衣壳名称
			31	20	AAV 214e
32	21	AAV 214e8
			33	22	AAV 214e9
34	23	AAV 214e10

实施例10

衣壳诱导的交叉中和抗体产生

AAV204和AAV214与AAV9 nAbs具有有限的或非常低的交叉反应性，并且诱导nAbs产物与AAV9交叉反应的可能性低。

我们测试了IM给予AAV9或AAV214的动物产生针对AAV9的中和抗体的能力。(图31A)。通过测定动物血清抑制AAV9转导的能力进行分析。萤光素酶载体导入允许的细胞类型，Lec2。转导后三天测定细胞的萤光素酶活性。每组由2或3只大鼠组成，用于对照，AAV9或AAV214。有利地，通过IM注射AAV214的动物未显示出对AAV9的交叉反应免疫反应，这可能导致较大的患者群体，因为包括了对AAV9预先存在免疫力的患者，无论是天然存在的还是由于先前给药。

在非人灵长类动物(NHP)中获得了类似的数据。AAV9鞘内(IT)和静脉内(IV)给予的NHP都产生针对AAV9的nAb(图31B)。IT给予的动物血清显示出对其它测试病毒(AAV204、AAV214和AAV6)高得多的交叉反应性。然而，我们相信给药途径对nAb的发育差异没有显著影响，因为两只动物通过鞘内加玻璃体内途径(IT+IV)给予AAV204也显示出交叉反应性的相似差异(图31C；参见NHP-2和NHP-3)。此外，仅玻璃体内(IVT)给予AAV204的动物(图31C；参见NHP-4)显示出与IT+IVT治疗的动物(NHP-3)相似的交叉反应性。所形成的交叉反应性的差异可能由产生nAbs的AAV衣壳蛋白表位的同一性来解释。用给予AAV9的动物血清样品均显示出对AAV204的低反应性(图31B)，并且三个AAV204治疗的动物中的两个显示出对AAV9和AAV214的非常低反应性，表明高相容性概率(图31C)。相比之下，AAV6在所有给予AAV204的动物中示出高交叉反应性(图31B和C)。

替代实施方案

1.一种编码包含与SEQ ID NO:3、30-34、49或84具有至少70％同一性的氨基酸序列的腺相关病毒(AAV)衣壳蛋白的多核苷酸，或编码包含与SEQ ID NO:1具有至少70％同一性的氨基酸序列的腺相关病毒(AAV)衣壳蛋白的多核苷酸的用途。

2.根据实施方案1所述的多核苷酸，其中所述氨基酸序列与SEQ ID NO:3、30-34、49或84具有至少80％的同一性。

3.根据实施方案1所述的多核苷酸，其中所述氨基酸序列与SEQ ID NO:3、30-34、49或84具有至少90％的同一性。

4.根据实施方案1所述的多核苷酸，其中所述氨基酸序列与SEQ ID NO:3、30-34、49或84具有至少95％的同一性。

5.根据实施方案1所述的多核苷酸，其中所述氨基酸序列与SEQ ID NO:3、30-34、49或84具有至少99％的同一性。

6.根据实施方案1所述的多核苷酸，其中所述氨基酸序列包含SEQ ID NO:3、30-34、49或84。

7.根据实施方案1-6中任一项所述的多核苷酸，其中所述氨基酸序列包含所述AAV衣壳蛋白的VP1部分、VP2部分、和VP3部分，并且其中所述VP3部分具有SEQ ID NO:41的序列。

8.根据实施方案7所述的多核苷酸，其中所述AAV衣壳蛋白与SEQ ID NO:3、30-34、49或84具有至少70％、80％、90％或99％的同一性。

9.根据实施方案1-8中任一项所述的多核苷酸，其中所述多核苷酸包含在质粒、细菌人工染色体、酵母人工染色体、噬菌体或病毒载体内。

10.一种宿主细胞，包含根据实施方案1-8中任一项所述的多核苷酸。

11.一种AAV衣壳蛋白，包含与SEQ ID NO:3、30-34、49或84具有至少70％、80％、90％或99％同一性的氨基酸序列。

12.一种AAV衣壳蛋白，包含具有SEQ ID NO2、3、30-34、49或84的序列的氨基酸序列。

13.一种AAV病毒载体，包含

(i)根据实施方案11或12所述的AAV衣壳蛋白，和

(ii)AAV载体。

14.根据实施方案13所述的AAV病毒载体，其中所述AAV载体包含异源核酸。

15.根据实施方案14所述的AAV病毒载体，其中所述异源核酸是转基因。

16.根据实施方案13至15所述的AAV病毒载体，其中所述转基因编码囊性纤维化跨膜传导调节蛋白(CFTR)、CLN3蛋白、α-半乳糖苷酶A(GLA)或酸性α-葡糖苷酶(GAA)。

17.根据实施方案15所述的AAV病毒载体，其中所述转基因包含与SEQ ID NO:5、6、7、9、10、12和13中的任一个具有至少70％、80％、90％或99％同一性的序列。

18.根据实施方案15所述的AAV病毒载体，其中所述转基因编码包含与SEQ ID NO:4、5、8、11和14中的任一个具有至少70％、80％、90％或99％同一性的氨基酸序列的蛋白质。

19.根据实施方案13至18所述的AAV病毒载体，其中所述异源核酸与启动子可操作地连接。

20.根据实施方案19所述的AAV病毒载体，其中所述启动子是组织特异性控制启动子或组成型启动子。

21.根据实施方案20所述的AAV病毒载体，其中所述启动子是组成型启动子，所述组成型启动子是劳斯肉瘤病毒(RSV)LTR启动子(任选地与RSV增强子一起)、巨细胞病毒(CMV)启动子、SV40启动子、二氢叶酸还原酶启动子、β-肌动蛋白启动子、磷酸甘油激酶(PGK)启动子、U6启动子、H1启动子、CAG启动子、杂合鸡β-肌动蛋白启动子、MeCP2启动子、EF1启动子、遍在鸡β-肌动蛋白杂合(CBh)启动子、U1a启动子、U1b启动子、MeCP2启动子、MeP418启动子、MeP426启动子、最小MeCP2启动子、VMD2启动子、mRho启动子、EFla启动子、Ubc启动子、人β-肌动蛋白启动子、TRE启动子、Ac5启动子、多角体蛋白启动子、CaMKIIa启动子、Gal1启动子、TEF1启动子、GDS启动子、ADH1启动子、Ubi启动子或α-1-抗胰蛋白酶(hAAT)启动子。

22.根据实施方案10所述的AAV病毒载体，其中所述启动子是组织特异性控制启动子，其是中枢神经系统(CNS)细胞特异性启动子、肺特异性启动子、皮肤特异性启动子、肌肉特异性启动子、肝特异性启动子或眼异性启动子。

23.根据实施方案14所述的AAV病毒载体，其中所述异源核酸编码mRNA、siRNA、gRNA或微RNA。

24.根据实施方案14所述的AAV病毒载体，其中所述异源核酸编码多肽。

25.根据实施方案14所述的AAV病毒载体，其中所述异源核酸编码囊性纤维化跨膜传导调节蛋白(CFTR)、CLN3蛋白、α-半乳糖苷酶A(GLA)或酸性α-葡糖苷酶(GAA)。

26.根据实施方案25所述的AAV病毒载体，其中所述异源核酸编码CFTR。

27.根据实施方案26所述的AAV病毒载体，其中所述CFTR包含SEQ ID NO:4编码的氨基酸序列或由其组成。

28.根据实施方案15所述的AAV病毒载体，其中所述异源核酸编码包含与SEQ IDNO:5、8、11和14中的任一个具有至少70％、80％、90％或99％同一性的氨基酸序列的蛋白质。

29.根据实施方案15所述的AAV病毒载体，其中所述异源核酸包含与SEQ ID NO:4、5、6、7、9、10、12和13中的任一个具有至少70％、80％、90％或99％同一性的序列。

30.根据实施方案18所述的AAV病毒载体，其中所述异源核酸编码报告蛋白。

31.一种将目标基因导入受试者细胞的方法，包括使细胞与有效量的根据实施方案13-30中任一项所述的AAV病毒载体接触。

32.根据实施方案31所述的方法，其中所述AAV病毒载体经口服、直肠、透粘膜、吸入、经皮、肠胃外、静脉内、皮下、皮内、肌内、胸膜内、脑内、鞘内、脑内、心室内、鼻内、耳内、眼内、眼周、局部、淋巴内、脑池内、鞘内或玻璃体内引入所述受试者。

33.根据实施方案31或32所述的方法，其中所述受试者是哺乳动物。

34.根据实施方案31至33所述的方法，其中所述受试者是人。

35.根据实施方案31至34所述的方法，其中所述细胞是体细胞。

36.根据实施方案35所述的方法，其中所述体细胞是神经细胞、视网膜细胞、肌肉细胞、上皮细胞、肺细胞、肝细胞、干细胞或皮肤细胞。

37.一种药物组合物，包含根据实施方案1-8中任一项所述的多核苷酸、根据实施方案11或12所述的AAV衣壳蛋白或根据实施方案13-30中任一项所述的AAV病毒载体。

38.一种治疗病症的方法，其包括向受试者施用治疗有效量的根据实施方案37所述的药物组合物。

39.根据实施方案38所述的方法，其中所述病症是CNS病症、皮肤病症、肺病症、肌肉病症、肺病症或视网膜病症。

40.根据实施方案38或39所述的方法，其中所述病症是肌萎缩性侧索硬化(ALS)、脊髓性肌萎缩(SMA)、法布里病、庞皮病、CLN3病(或青少年神经元蜡样质脂褐质沉积症)、隐性营养不良性大疱性表皮松解症(RDEB)、青少年巴特氏病、常染色体显性病症、肌营养不良、血友病A、血友病B、多发性硬化、糖尿病、戈谢病、癌症、关节炎、肌肉消瘦、心脏病、内膜增生、癫痫、亨延顿氏舞蹈病、帕金森病、阿尔茨海默病、囊性纤维化、地中海贫血、赫尔勒综合征、Sly综合征、沙伊综合征、胡-射二氏综合征、亨特综合征、Sanfilippo综合征A(粘多糖贮积病IIIA或MPS IIIA)、Sanfilippo综合征B(粘多糖贮积病IIIB或MPS IIIB)、Sanfilippo综合征C、Sanfilippo综合征D、莫基奥综合征、马-兰二氏综合征、克腊比氏病、苯丙酮尿症、巴特氏病、脊髓小脑性共济失调、LDL受体缺乏、高血氨症、关节炎、黄斑变性、色素性视网膜炎、神经元蜡样质脂褐质沉积症1(CLN1)或腺苷脱氨酶缺乏。

41.根据实施方案38所述的方法，其中所述病症是脊髓性肌萎缩(SMA)、隐性营养不良性大疱性表皮松解症(RDEB)、法布里病、庞皮病、CLN3病(或青少年神经元蜡样质脂褐质沉积症)、MPS IIIA、MPS IIIB、青少年巴特氏病和杜兴氏肌营养不良(DMD)或贝克肌营养不良。

42.根据实施方案38所述的方法，其中所述病症是癌症，并且所述癌症是膀胱癌、乳腺癌、宫颈癌、结肠癌、直肠癌、子宫内膜癌、肾癌、唇癌、口腔癌、肝癌、黑素瘤、间皮瘤、非小细胞肺癌、非黑素瘤皮肤癌、口腔癌、卵巢癌、胰腺癌、前列腺癌、肉瘤、小细胞肺癌或甲状腺癌。

43.根据实施方案37至42所述的方法，其中所述受试者是哺乳动物。

44.根据实施方案43所述的方法，其中所述受试者是人。

45.一种试剂盒，包含根据实施方案1-8中任一项所述的多核苷酸、根据实施方案10所述的细胞、根据实施方案12或13所述的AAV衣壳蛋白和/或根据实施方案13-30中任一项所述的AAV病毒载体。

46.一种AAV包装系统，包含

根据实施方案1-8中任一项所述的多核苷酸，以及辅助细胞。

47.根据根据实施方案46所述的AAV包装系统，其中所述辅助细胞是酵母细胞、

哺乳动物细胞或昆虫细胞。

48.一种编码AAV衣壳蛋白的核酸，所述AAV衣壳蛋白包含在氨基酸129处的亮氨酸残基、在氨基酸586处的天冬酰胺残基和在氨基酸723处的谷氨酸残基，其中所述AAV衣壳蛋白中的氨基酸位置相对于SEQ ID NO:2的氨基酸序列中的氨基酸位置进行编号。

49.根据实施方案48所述的核酸，其中所述编码的AAV衣壳氨基酸序列与SEQ IDNO:2的氨基酸序列具有至少95％的同一性。

50.根据实施方案48所述的核酸，其中所述编码的AAV衣壳氨基酸序列与SEQ IDNO:2的氨基酸序列具有至少99％的同一性。

51.根据实施方案48所述的核酸，其中所述核酸序列与SEQ ID NO:15的核苷酸序列具有至少99％的同一性。

52.根据实施方案48所述的核酸，其中所述核酸序列与SEQ ID NO:15的核苷酸序列具有100％的同一性。

53.一种载体，包含根据实施方案48至52所述的核酸。

54.一种AAV衣壳蛋白，由根据实施方案48至52所述的核酸编码。

55.根据实施方案54所述的AAV衣壳蛋白，其中所述蛋白包含SEQ ID NO:2的氨基酸序列。

56.一种AAV病毒载体，包含由根据实施方案54或55所述的核酸编码的所述AAV衣壳蛋白和AAV载体，其中所述AAV载体包含异源核酸。

57.根据实施方案56所述的AAV病毒载体，其中所述异源核酸与组成型启动子可操作地连接。

58.根据实施方案56或57所述的AAV病毒载体，其中所述异源核酸编码多肽。

59.根据实施方案56或57所述的AAV病毒载体，其中异源核酸编码反义RNA、微RNA或RNAi。

60.根据实施方案56所述的AAV病毒载体，其中所述AAV衣壳蛋白包含SEQ ID NO:2的氨基酸序列。

61.一种编码AAV衣壳蛋白的核酸，所述AAV衣壳蛋白包含VP1部分、VP2部分和VP3部分，其中所述VP3部分包含可变区(VR)I至IX，其中：

(a)VR-II包含氨基酸序列DNNGVK(SEQ ID NO:54)；

(b)VR-III包含氨基酸序列NDGS(SEQ ID NO:55)；

(c)VR-IV包含氨基酸序列INGSGQNQQT(SEQ ID NO:56)；

(d)VR-V包含氨基酸序列RVSTTTGQNNNSNFAWTA(SEQ ID NO:57)；

(e)VR-VI包含氨基酸序列HKEGEDRFFPLSG(SEQ ID NO:58)；

(f)VR-VII包含氨基酸序列KQNAARDNADYSDV(SEQ ID NO:59)；

(g)VR-VIII包含氨基酸序列ADNLQQQNTAPQI(SEQ ID NO:60)；以及

(h)VR-IX包含氨基酸序列NYYKSTSVDF(SEQ ID NO:61)。

62.根据实施方案61所述的核酸，其中所述VR-I区包含SASTGAS(SEQ ID NO:52)。

63.根据实施方案61所述的核酸，其中所述VR-I区包含NSTSGGSS(SEQ ID NO:53)或SSTSGGSS(SEQ ID NO:87)。

64.根据实施方案61至63所述的核酸，其中所述VP3部分还包含下列中的一者或多者：

(i)在氨基酸223处的天冬酰胺(N)；

(ii)在氨基酸224处的丙氨酸(A)残基；

(iii)在氨基酸410处的苏氨酸(T)残基；

(iv)在氨基酸724处的组氨酸残基；以及

(v)在氨基酸734处的脯氨酸(P)残基，

其中所述AAV衣壳蛋白中的氨基酸位置相对于SEQ ID NO:3的氨基酸序列中的氨基酸位置进行编号。

65.根据实施方案61至64所述的核酸，其中所述编码的AAV衣壳氨基酸序列与SEQID NO:3、30、31、32、33、34、49或84的氨基酸序列具有至少95％的同一性。

66.根据实施方案61至65所述的核酸，其中所述编码的AAV衣壳氨基酸序列与SEQID NO:3、30、31、32、33、34、49或84的氨基酸序列具有至少99％的同一性。

67.根据实施方案61至66所述的核酸，其中所述核酸序列与选自SEQ ID NO:18、19、20、21、22、23、47、82或98的核苷酸序列具有至少99％的同一性。

68.根据实施方案61所述的核酸，其中所述核酸序列与选自SEQ ID NO:18、19、20、21、22、23、47、82或98的核苷酸序列具有100％的同一性。

69.一种载体，包含根据实施方案61至68所述的核酸。

70.一种AAV衣壳蛋白，由根据实施方案61至68所述的核酸编码。

71.根据实施方案70所述的AAV衣壳蛋白，其中所述蛋白质包含SEQ ID NO:3、30、31、32、33、34、49或84的氨基酸序列。

72.一种AAV病毒载体，包含由根据实施方案61至68所述的核酸编码的AAV衣壳蛋白和AAV载体，其中所述AAV载体包含异源核酸。

73.根据实施方案72所述的AAV病毒载体，其中所述异源核酸与组成型启动子可操作地连接。

74.根据实施方案72或73所述的AAV病毒载体，其中所述异源核酸编码多肽。

75.根据实施方案72或73所述的AAV病毒载体，其中所述异源核酸编码反义RNA、微RNA或RNAi。

76.根据实施方案72至75所述的AAV病毒载体，其中所述AAV衣壳蛋白包含SEQ IDNO:3、30、31、32、33、34、49或84的氨基酸序列。

77.一种编码AAV衣壳蛋白的核酸，所述AAV衣壳蛋白包含VP1部分、VP2部分和VP3部分，其中所述VP3部分包含可变区(VR)I至IX，其中：

(a)VR-I包含氨基酸序列SASTGAS(SEQ ID NO:52)

(b)VR-II包含氨基酸序列DNNGVK(SEQ ID NO:54)；

(c)VR-III包含氨基酸序列NDGS(SEQ ID NO:55)；

(d)VR-IV包含氨基酸序列INGSGQNQQT(SEQ ID NO:56)；

(e)VR-V包含氨基酸序列RVSTTTGQNNNSNFAWTA(SEQ ID NO:57)；

(f)VR-VI包含氨基酸序列HKEGEDRFFPLSG(SEQ ID NO:58)；

(g)VR-VII包含氨基酸序列KQNAARDNADYSDV(SEQ ID NO:59)；

(h)VR-VIII包含氨基酸序列ADNLQQQNTAPQI(SEQ ID NO:60)；以及

(i)VR-IX包含氨基酸序列NYYKSTSVDF(SEQ ID NO:61)。

78.根据实施方案77所述的核酸，其中所述VP3部分还包含下列中的一者或多者：

(i)在氨基酸223处的天冬酰胺(N)；

(ii)在氨基酸224处的丙氨酸(A)残基；

(iii)在氨基酸410处的苏氨酸(T)残基；

(iv)在氨基酸724处的组氨酸残基；以及

(v)在氨基酸734处的脯氨酸(P)残基，

79.根据实施方案77或78所述的核酸，其中所述VP3部分具有SEQ ID NO:41的序列。

80.根据实施方案77至79所述的核酸，其中所述编码的AAV衣壳氨基酸序列的所述VP1和所述VP2部分与SEQ ID NO:3、31、32、33或34的所述VP1和所述VP2部分的氨基酸序列具有至少95％的同一性。

81.根据实施方案77至80所述的核酸，其中所述编码的AAV衣壳氨基酸序列与SEQID NO:3、31、32、33或34的氨基酸序列具有至少99％的同一性。

82.根据实施方案77至81所述的核酸，其中所述核酸序列与选自SEQ ID NO:18、20、21、22或23的核苷酸序列具有至少99％的同一性。

83.根据实施方案77至82所述的核酸，其中所述核酸序列与选自SEQ ID NO:18、20、21、22或23的核苷酸序列具有100％的同一性。

84.一种载体，包含根据实施方案57至83所述的核酸。

85.一种AAV衣壳蛋白，由根据实施方案77至83所述的核酸编码。

86.根据实施方案85所述的AAV衣壳蛋白，其中所述蛋白包含SEQ ID NO:3、31、32、33或34的氨基酸序列。

87.一种AAV病毒载体，包含由根据实施方案88所述的核酸编码的AAV衣壳蛋白和AAV载体，其中所述AAV载体包含异源核酸。

88.根据实施方案87所述的AAV病毒载体，其中所述异源核酸与组成型启动子可操作地连接。

89.根据实施方案87或88所述的AAV病毒载体，其中所述异源核酸编码多肽。

90.根据实施方案87或88所述的AAV病毒载体，其中所述异源核酸编码反义RNA、微RNA或RNAi。

91.根据实施方案87～90所述的AAV病毒载体，其中所述AAV衣壳蛋白包含SEQ IDNO:3、31、32、33或34的氨基酸序列。

92.一种编码AAV衣壳蛋白的核酸，所述AAV衣壳蛋白包含VP1部分、VP2部分和VP3部分，其中所述VP1部分包含在氨基酸129处的亮氨酸(L)残基，其中所述VP2部分包含在氨基酸157处的苏氨酸(T)或天冬酰胺(N)残基和在氨基酸162处的赖氨酸(K)或丝氨酸(S)残基，并且其中所述VP3部分包含在氨基酸223处的天冬酰胺(N)残基、在氨基酸224处的丙氨酸(A)残基、在氨基酸272处的组氨酸(H)残基、在氨基酸410处的苏氨酸(T)残基、在氨基酸724处的组氨酸(H)残基和在氨基酸734处的脯氨酸(P)残基，其中所述AAV衣壳蛋白衣壳中的氨基酸位置相对于SEQ ID NO:3的氨基酸序列中的氨基酸位置进行编号。

93.根据实施方案92所述的核酸，其中所述VP3部分包含可变区(VR)I至IX，其中：

(a)VR-I包含氨基酸序列SASTGAS(SEQ ID NO:52)；

(b)VR-II包含氨基酸序列DNNGVK(SEQ ID NO:54)；

(c)VR-III包含氨基酸序列NDGS(SEQ ID NO:55)；

(d)VR-IV包含氨基酸序列INGSGQNQQT(SEQ ID NO:56)；

(e)VR-V包含氨基酸序列RVSTTTGQNNNSNFAWTA(SEQ ID NO:57)；

(f)VR-VI包含氨基酸序列HKEGEDRFFPLSG(SEQ ID NO:58)；

(g)VR-VII包含氨基酸序列KQNAARDNADYSDV(SEQ ID NO:59)；

(h)VR-VIII包含氨基酸序列ADNLQQQNTAPQI(SEQ ID NO:60)；以及

(i)VR-IX包含氨基酸序列NYYKSTSVDF(SEQ ID NO:61)。

94.根据实施方案92或93所述的核酸，其中所述VP1部分还在氨基酸24处包含天冬氨酸(D)或丙氨酸(A)残基，其中所述AAV衣壳蛋白中的氨基酸位置相对于SEQ ID NO:3的氨基酸序列中的氨基酸位置进行编号。

95.根据实施方案92至94所述的核酸，其中所述VP2部分还包含下列中的一者或多者：

(i)在氨基酸148处的脯氨酸(P)残基；

(ii)在氨基酸152处插入的精氨酸(R)残基；

(iii)在氨基酸168处的精氨酸(R)残基；

(iv)在氨基酸189处的异亮氨酸(I)残基；以及

(v)在氨基酸200处的丝氨酸(S)残基，

96.根据实施方案92至96所述的核酸，其中所述编码的AAV衣壳氨基酸序列与SEQID NO:31、32、33或34的氨基酸序列具有至少95％的同一性。

97.根据实施方案92所述的核酸，其中所述编码的AAV衣壳氨基酸序列与SEQ IDNO:31、32、33或34的氨基酸序列具有至少99％的同一性。

98.根据实施方案92所述的核酸，其中所述核酸序列与选自SEQ ID NO:20、21、22或23的核苷酸序列具有至少99％的同一性。

99.根据实施方案98所述的核酸，其中所述核酸序列与选自SEQ ID NO:20、21、22或23的核苷酸序列具有100％的同一性。

100.一种载体，包含根据实施方案92至99所述的核酸。

101.一种AAV衣壳蛋白，由根据实施方案92至99所述的核酸编码。

102.根据实施方案101所述的AAV衣壳蛋白，其中所述蛋白包含SEQ ID NO:31、32、33或34的氨基酸序列。

103.一种AAV病毒载体，包含由根据实施方案101或102所述的核酸编码的所述AAV衣壳蛋白和AAV载体，其中所述AAV载体包含异源核酸。

104.根据实施方案103所述的AAV病毒载体，其中所述异源核酸与组成型启动子可操作地连接。

105.根据实施方案103或104所述的AAV病毒载体，其中所述异源核酸编码多肽、反义RNA、微RNA或RNAi。

序列表

<110> 阿贝奥纳治疗有限公司

<120> 用于基因递送的重组腺相关病毒载体

<130> ABEO-002/04WO 337067-2028

<150> US 62/914,856

<151> 2019-10-14

<150> US 62/863,126

<151> 2019-06-18

<150> US 62/801,195

<151> 2019-02-05

<150> US 62/775,871

<151> 2018-12-05

<160> 163

<170> PatentIn 3.5版

<210> 1

<211> 737

<212> PRT

<213> 人工序列

<220>

<223> AAV110 VPl

<400> 1

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro

180 185 190

Pro Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn

210 215 220

Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn

260 265 270

His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn

370 375 380

Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn

435 440 445

Arg Thr Gln Asn Gln Ser Gly Ser Ala Gln Asn Lys Asp Leu Leu Phe

450 455 460

Ser Arg Gly Ser Pro Ala Gly Met Ser Val Gln Pro Lys Asn Trp Leu

465 470 475 480

Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Lys Thr Asp

485 490 495

Asn Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Ser Lys Tyr Asn Leu

500 505 510

Asn Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr Ala Met Ala Ser His

515 520 525

Lys Asp Asp Lys Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe

530 535 540

Gly Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val Met

545 550 555 560

Ile Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu

565 570 575

Arg Phe Gly Thr Val Ala Val Asn Leu Gln Ser Ser Ser Thr Asp Pro

580 585 590

Ala Thr Gly Asp Val His Val Met Gly Ala Leu Pro Gly Met Val Trp

595 600 605

Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro

610 615 620

His Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly

625 630 635 640

Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro

645 650 655

Ala Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile

660 665 670

Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu

675 680 685

Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Val Gln Tyr Thr Ser

690 695 700

Asn Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn Gly

705 710 715 720

Leu Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro

725 730 735

Leu

<210> 2

<211> 736

<212> PRT

<213> 人工序列

<220>

<223> AAV204 VP1

<400> 2

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His

260 265 270

Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe

275 280 285

His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn

290 295 300

Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln

305 310 315 320

Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn

325 330 335

Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro

340 345 350

Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala

355 360 365

Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly

370 375 380

Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro

385 390 395 400

Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe

405 410 415

Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp

420 425 430

Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg

435 440 445

Thr Gln Asn Gln Ser Gly Ser Ala Gln Asn Lys Asp Leu Leu Phe Ser

450 455 460

Arg Gly Ser Pro Ala Gly Met Ser Val Gln Pro Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Lys Thr Asp Asn

485 490 495

Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Ser Lys Tyr Asn Leu Asn

500 505 510

Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr Ala Met Ala Ser His Lys

515 520 525

Asp Asp Lys Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Gly

530 535 540

Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val Met Ile

545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Arg

565 570 575

Phe Gly Thr Val Ala Val Asn Leu Gln Asn Ser Ser Thr Asp Pro Ala

580 585 590

Thr Gly Asp Val His Val Met Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Val Gln Tyr Thr Ser Asn

690 695 700

Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn Gly Leu

705 710 715 720

Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 3

<211> 735

<212> PRT

<213> 人工序列

<220>

<223> AAV214 VPl

<400> 3

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Phe Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His

260 265 270

Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe

275 280 285

His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn

290 295 300

Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln

305 310 315 320

Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn Asn

325 330 335

Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu Pro

340 345 350

Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala

355 360 365

Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp Gly

370 375 380

Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro

385 390 395 400

Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe

405 410 415

Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp

420 425 430

Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Lys

435 440 445

Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser Gln

450 455 460

Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu Pro Gly

465 470 475 480

Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln Asn Asn

485 490 495

Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu Asn Gly

500 505 510

Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys Glu

515 520 525

Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly Lys

530 535 540

Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val Met Leu Thr

545 550 555 560

Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Glu Tyr

565 570 575

Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln Ile

580 585 590

Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln Asn

595 600 605

Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr

610 615 620

Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys

625 630 635 640

His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp

645 650 655

Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr Gln

660 665 670

Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys

675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr

690 695 700

Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly Val Tyr

705 710 715 720

Ser Glu Pro His Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 4

<211> 4287

<212> DNA

<213> 人工序列

<220>

<223> CFTR△R

<400> 4

atgcagagaa gccccctgga gaaggcctct gtggtgagca agctgttctt cagctggacc 60

agacccatcc tgagaaaggg ctacagacag agactggagc tgtctgacat ctaccagatc 120

ccctctgtgg actctgctga caacctgtct gagaagctgg agagagagtg ggacagagag 180

ctggccagca agaagaaccc caagctgatc aatgccctga gaagatgctt cttctggaga 240

ttcatgttct atggcatctt cctgtacctg ggggaggtga ccaaggctgt gcagcccctg 300

ctgctgggca gaatcattgc cagctatgac cctgacaaca aggaggagag aagcattgcc 360

atctacctgg gcattggcct gtgcctgctg ttcattgtga gaaccctgct gctgcaccct 420

gccatctttg gcctgcacca cattggcatg cagatgagaa ttgccatgtt cagcctgatc 480

tacaagaaga ccctgaagct gagcagcaga gtgctggaca agatcagcat tggccagctg 540

gtgagcctgc tgagcaacaa cctgaacaag tttgatgagg gcctggccct ggcccacttt 600

gtgtggattg cccccctgca ggtggccctg ctgatgggcc tgatctggga gctgctgcag 660

gcctctgcct tctgtggcct gggcttcctg attgtgctgg ccctgttcca ggctggcctg 720

ggcagaatga tgatgaagta cagagaccag agagctggca agatctctga gagactggtg 780

atcacctctg agatgattga gaacatccag tctgtgaagg cctactgctg ggaggaggcc 840

atggagaaga tgattgagaa cctgagacag acagagctga agctgaccag aaaggctgcc 900

tatgtgagat acttcaacag ctctgccttc ttcttctctg gcttctttgt ggtgttcctg 960

tctgtgctgc cctatgccct gatcaagggc atcatcctga gaaagatctt caccaccatc 1020

agcttctgca ttgtgctgag aatggctgtg accagacagt tcccctgggc tgtgcagacc 1080

tggtatgaca gcctgggggc catcaacaag atccaggact tcctgcagaa gcaggagtac 1140

aagaccctgg agtacaacct gaccaccaca gaggtggtga tggagaatgt gacagccttc 1200

tgggaggagg gctttgggga gctgtttgag aaggccaagc agaacaacaa caacagaaag 1260

accagcaatg gggatgacag cctgttcttc agcaacttca gcctgctggg cacccctgtg 1320

ctgaaggaca tcaacttcaa gattgagaga ggccagctgc tggctgtggc tggcagcaca 1380

ggggctggca agaccagcct gctgatgatg atcatggggg agctggagcc ctctgagggc 1440

aagatcaagc actctggcag aatcagcttc tgcagccagt tcagctggat catgcctggc 1500

accatcaagg agaacatcat ctttggggtg agctatgatg agtacagata cagatctgtg 1560

atcaaggcct gccagctgga ggaggacatc agcaagtttg ctgagaagga caacattgtg 1620

ctgggggagg ggggcatcac cctgtctggg ggccagagag ccagaatcag cctggccaga 1680

gctgtgtaca aggatgctga cctgtacctg ctggacagcc cctttggcta cctggatgtg 1740

ctgacagaga aggagatctt tgagagctgt gtgtgcaagc tgatggccaa caagaccaga 1800

atcctggtga ccagcaagat ggagcacctg aagaaggctg acaagatcct gatcctgcat 1860

gagggcagca gctacttcta tggcaccttc tctgagctgc agaacctgca gcctgacttc 1920

agcagcaagc tgatgggctg tgacagcttt gaccagttct ctgctgagag aagaaacagc 1980

atcctgacag agaccctgca cagattcagc ctggaggggg atgcccctgt gagctggaca 2040

gagaccaaga agcagagctt caagcagaca ggggagtttg gggagaagag aaagaacagc 2100

atcctgaacc ccatcaacag caccctgcag gccagaagaa gacagtctgt gctgaacctg 2160

atgacccact ctgtgaacca gggccagaac atccacagaa agaccacagc cagcaccaga 2220

aaggtgagcc tggcccccca ggccaacctg acagagctgg acatctacag cagaagactg 2280

agccaggaga caggcctgga gatctctgag gagatcaatg aggaggacct gaaggagtgc 2340

ttctttgatg acatggagag catccctgct gtgaccacct ggaacaccta cctgagatac 2400

atcacagtgc acaagagcct gatctttgtg ctgatctggt gcctggtgat cttcctggct 2460

gaggtggctg ccagcctggt ggtgctgtgg ctgctgggca acacccccct gcaggacaag 2520

ggcaacagca cccacagcag aaacaacagc tatgctgtga tcatcaccag caccagcagc 2580

tactatgtgt tctacatcta tgtgggggtg gctgacaccc tgctggccat gggcttcttc 2640

agaggcctgc ccctggtgca caccctgatc acagtgagca agatcctgca ccacaagatg 2700

ctgcactctg tgctgcaggc ccccatgagc accctgaaca ccctgaaggc tgggggcatc 2760

ctgaacagat tcagcaagga cattgccatc ctggatgacc tgctgcccct gaccatcttt 2820

gacttcatcc agctgctgct gattgtgatt ggggccattg ctgtggtggc tgtgctgcag 2880

ccctacatct ttgtggccac agtgcctgtg attgtggcct tcatcatgct gagagcctac 2940

ttcctgcaga ccagccagca gctgaagcag ctggagtctg agggcagaag ccccatcttc 3000

acccacctgg tgaccagcct gaagggcctg tggaccctga gagcctttgg cagacagccc 3060

tactttgaga ccctgttcca caaggccctg aacctgcaca cagccaactg gttcctgtac 3120

ctgagcaccc tgagatggtt ccagatgaga attgagatga tctttgtgat cttcttcatt 3180

gctgtgacct tcatcagcat cctgaccaca ggggaggggg agggcagagt gggcatcatc 3240

ctgaccctgg ccatgaacat catgagcacc ctgcagtggg ctgtgaacag cagcattgat 3300

gtggacagcc tgatgagatc tgtgagcaga gtgttcaagt tcattgacat gcccacagag 3360

ggcaagccca ccaagagcac caagccctac aagaatggcc agctgagcaa ggtgatgatc 3420

attgagaaca gccatgtgaa gaaggatgac atctggccct ctgggggcca gatgacagtg 3480

aaggacctga cagccaagta cacagagggg ggcaatgcca tcctggagaa catcagcttc 3540

agcatcagcc ctggccagag agtgggcctg ctgggcagaa caggctctgg caagagcacc 3600

ctgctgtctg ccttcctgag actgctgaac acagaggggg agatccagat tgatggggtg 3660

agctgggaca gcatcaccct gcagcagtgg agaaaggcct ttggggtgat cccccagaag 3720

gtgttcatct tctctggcac cttcagaaag aacctggacc cctatgagca gtggtctgac 3780

caggagatct ggaaggtggc tgatgaggtg ggcctgagat ctgtgattga gcagttccct 3840

ggcaagctgg actttgtgct ggtggatggg ggctgtgtgc tgagccatgg ccacaagcag 3900

ctgatgtgcc tggccagatc tgtgctgagc aaggccaaga tcctgctgct ggatgagccc 3960

tctgcccacc tggaccctgt gacctaccag atcatcagaa gaaccctgaa gcaggccttt 4020

gctgactgca cagtgatcct gtgtgagcac agaattgagg ccatgctgga gtgccagcag 4080

ttcctggtga ttgaggagaa caaggtgaga cagtatgaca gcatccagaa gctgctgaat 4140

gagagaagcc tgttcagaca ggccatcagc ccctctgaca gagtgaagct gttcccccac 4200

agaaacagca gcaagtgcaa gagcaagccc cagattgctg ccctgaagga ggagaccgag 4260

gaggaggtgc aggacaccag actgtaa 4287

<210> 5

<211> 2859

<212> DNA

<213> 人工序列

<220>

<223> GAA

<400> 5

atgggagtcc gccacccgcc ctgctcacat cgcctgcttg ctgtctgtgc cctcgtgtca 60

cttgctaccg ccgcgctgct tggtcacatt ctgctgcacg actttttact agttccgagg 120

gaactgtcgg gatccagccc cgtgctcgag gaaactcacc ccgcgcacca acagggggcg 180

tccaggccgg gaccgcgcga cgcccaggcc cacccgggcc ggcctcgggc cgtgccaact 240

cagtgcgatg tgccgccgaa ctcccgcttc gactgtgcgc ctgacaaggc cataacccag 300

gaacagtgcg aagcacgcgg ctgctgctat attccggcga agcagggctt gcagggtgcc 360

caaatgggtc agccttggtg cttctttccc ccgtcgtacc cctcgtacaa gctggagaac 420

ctgagcagca gcgaaatggg gtacaccgcc actctgaccc ggacgacccc gaccttcttc 480

ccgaaagaca tcctgaccct gcggctggat gtgatgatgg aaactgagaa cagactgcac 540

ttcactatca aggaccccgc gaaccgcaga tatgaggtgc cactggaaac ccctcatgtg 600

cattcccggg ccccatcccc tctgtactcg gtggaattct ccgaagaacc cttcggggtc 660

attgtgcgcc ggcagcttga tggccgggtc ctgctcaaca ccaccgtggc accccttttc 720

ttcgctgacc agttcctcca gctgagcacc tcgctgccga gccagtacat caccggactg 780

gccgagcacc tctcccctct gatgctgtcc actagctgga ctaggatcac tctgtggaac 840

cgggatctgg cccctacccc gggcgcgaac ctgtacggat cgcacccctt ctacctggcc 900

ctcgaggacg gaggctccgc ccacggagtg ttcctgctga actccaacgc tatggacgtg 960

gtgctccagc cgtcccctgc actgtcctgg cggagcacag ggggtattct ggatgtctac 1020

atcttcctcg gcccggagcc aaagtccgtg gtgcaacagt atctggatgt cgtgggttac 1080

ccattcatgc cgccatactg gggccttggc ttccacctgt gccgctgggg atacagctcc 1140

accgccatca ctagacaggt cgtggaaaac atgactagag cccacttccc cctcgatgtc 1200

cagtggaatg acctggacta catggattcc agacgcgact tcactttcaa caaggatgga 1260

ttcagagatt tccccgctat ggtccaagaa ctgcaccagg gtggccggcg gtacatgatg 1320

attgtggacc ccgccatttc aagctccgga ccagcgggct cgtaccggcc ctacgacgaa 1380

ggtttgcgcc gcggcgtgtt catcactaac gaaaccggcc agccactgat tgggaaggtc 1440

tggcctggaa gcaccgcgtt cccggacttc actaacccaa cggccttggc gtggtgggag 1500

gacatggtgg ccgaattcca cgaccaagtc ccattcgacg gaatgtggat cgacatgaac 1560

gagcccagca acttcatccg aggctccgag gacggctgcc ctaacaacga acttgagaac 1620

cctccgtacg tgcctggcgt cgtcggcgga acactgcagg ccgctacgat ctgtgcctca 1680

tcgcatcagt tcctgtcaac ccactacaac ctccataatc tgtacggcct caccgaagcc 1740

atcgcctccc accgggccct ggtcaaggcc cgggggacta ggcccttcgt gattagccgg 1800

agcactttcg ccggacacgg aagatacgcc ggacattgga ccggcgacgt gtggtcatcg 1860

tgggagcagc tcgcctcctc cgtccccgaa atcctgcagt tcaatctcct gggagtcccc 1920

ctcgtgggcg cggacgtgtg cggattcctg ggcaatacct ctgaggagct gtgcgtgaga 1980

tggacccagc tgggggcgtt ctaccccttc atgcggaacc acaactcact gctgtccctg 2040

cctcaagagc cgtactcatt ctccgagccg gcacaacagg ccatgcgaaa ggctctgacc 2100

ctccgctatg cgctcttgcc ccacctctac actctgtttc accaagccca tgtcgcgggc 2160

gaaacagtgg ccagaccact ctttctggaa ttcccaaagg actcctcaac ctggactgtg 2220

gatcatcagc tgctctgggg agaggcactg ctgatcaccc cggtgctcca agccggaaag 2280

gcggaagtga ccggatactt ccctctcggt acttggtacg acctccaaac cgtgccggtc 2340

gaggccctgg gcagcttgcc tccgccgccg gctgccccgc gggagcctgc aatccactcc 2400

gaggggcaat gggtgaccct ccctgcacca ctggacacca tcaacgtgca cctccgggcc 2460

ggctacatca tcccgctgca aggaccgggt ctgactacca ccgaatcccg gcagcagccc 2520

atggcactgg ccgtggccct gaccaaggga ggggaagcac ggggagaact cttttgggac 2580

gatggagaat ccctggaagt gctcgagcgg ggagcctaca ctcaagtcat ctttcttgcc 2640

cgcaacaaca ccatcgtgaa cgaattggtc cgcgtgacct ccgagggggc cggactccag 2700

ctgcaaaaag tgaccgtgct gggggtggca accgccccgc aacaagtgtt gtctaacgga 2760

gtgccggtgt ccaacttcac ctactcccct gataccaaag ttctagatat ttgcgtgagc 2820

ctgctgatgg gagaacagtt cctggtgtcc tggtgctga 2859

<210> 6

<211> 2859

<212> DNA

<213> 人工序列

<220>

<223> GAA密码子优化的核苷酸序列1 (GAA 15)

<400> 6

atgggagtcc gccacccgcc ctgctcacat cgcctgcttg ctgtctgtgc cctcgtgtca 60

cttgctaccg ccgcgctgct tggtcacatt ctgctgcacg actttttact agttccgagg 120

gaactgtcgg gatccagccc cgtgctcgag gaaactcacc ccgcgcacca acagggggcg 180

tccaggccgg gaccgcgcga cgcccaggcc cacccgggcc ggcctcgggc cgtgccaact 240

cagtgcgatg tgccgccgaa ctcccgcttc gactgtgcgc ctgacaaggc cataacccag 300

gaacagtgcg aagcacgcgg ctgctgctat attccggcga agcagggctt gcagggtgcc 360

caaatgggtc agccttggtg cttctttccc ccgtcgtacc cctcgtacaa gctggagaac 420

ctgagcagca gcgaaatggg gtacaccgcc actctgaccc ggacgacccc gaccttcttc 480

ccgaaagaca tcctgaccct gcggctggat gtgatgatgg aaactgagaa cagactgcac 540

ttcactatca aggaccccgc gaaccgcaga tatgaggtgc cactggaaac ccctcatgtg 600

cattcccggg ccccatcccc tctgtactcg gtggaattct ccgaagaacc cttcggggtc 660

attgtgcgcc ggcagcttga tggccgggtc ctgctcaaca ccaccgtggc accccttttc 720

ttcgctgacc agttcctcca gctgagcacc tcgctgccga gccagtacat caccggactg 780

gccgagcacc tctcccctct gatgctgtcc actagctgga ctaggatcac tctgtggaac 840

cgggatctgg cccctacccc gggcgcgaac ctgtacggat cgcacccctt ctacctggcc 900

ctcgaggacg gaggctccgc ccacggagtg ttcctgctga actccaacgc tatggacgtg 960

gtgctccagc cgtcccctgc actgtcctgg cggagcacag ggggtattct ggatgtctac 1020

atcttcctcg gcccggagcc aaagtccgtg gtgcaacagt atctggatgt cgtgggttac 1080

ccattcatgc cgccatactg gggccttggc ttccacctgt gccgctgggg atacagctcc 1140

accgccatca ctagacaggt cgtggaaaac atgactagag cccacttccc cctcgatgtc 1200

cagtggaatg acctggacta catggattcc agacgcgact tcactttcaa caaggatgga 1260

ttcagagatt tccccgctat ggtccaagaa ctgcaccagg gtggccggcg gtacatgatg 1320

attgtggacc ccgccatttc aagctccgga ccagcgggct cgtaccggcc ctacgacgaa 1380

ggtttgcgcc gcggcgtgtt catcactaac gaaaccggcc agccactgat tgggaaggtc 1440

tggcctggaa gcaccgcgtt cccggacttc actaacccaa cggccttggc gtggtgggag 1500

gacatggtgg ccgaattcca cgaccaagtc ccattcgacg gaatgtggat cgacatgaac 1560

gagcccagca acttcatccg aggctccgag gacggctgcc ctaacaacga acttgagaac 1620

cctccgtacg tgcctggcgt cgtcggcgga acactgcagg ccgctacgat ctgtgcctca 1680

tcgcatcagt tcctgtcaac ccactacaac ctccataatc tgtacggcct caccgaagcc 1740

atcgcctccc accgggccct ggtcaaggcc cgggggacta ggcccttcgt gattagccgg 1800

agcactttcg ccggacacgg aagatacgcc ggacattgga ccggcgacgt gtggtcatcg 1860

tgggagcagc tcgcctcctc cgtccccgaa atcctgcagt tcaatctcct gggagtcccc 1920

ctcgtgggcg cggacgtgtg cggattcctg ggcaatacct ctgaggagct gtgcgtgaga 1980

tggacccagc tgggggcgtt ctaccccttc atgcggaacc acaactcact gctgtccctg 2040

cctcaagagc cgtactcatt ctccgagccg gcacaacagg ccatgcgaaa ggctctgacc 2100

ctccgctatg cgctcttgcc ccacctctac actctgtttc accaagccca tgtcgcgggc 2160

gaaacagtgg ccagaccact ctttctggaa ttcccaaagg actcctcaac ctggactgtg 2220

gatcatcagc tgctctgggg agaggcactg ctgatcaccc cggtgctcca agccggaaag 2280

gcggaagtga ccggatactt ccctctcggt acttggtacg acctccaaac cgtgccggtc 2340

gaggccctgg gcagcttgcc tccgccgccg gctgccccgc gggagcctgc aatccactcc 2400

gaggggcaat gggtgaccct ccctgcacca ctggacacca tcaacgtgca cctccgggcc 2460

ggctacatca tcccgctgca aggaccgggt ctgactacca ccgaatcccg gcagcagccc 2520

atggcactgg ccgtggccct gaccaaggga ggggaagcac ggggagaact cttttgggac 2580

gatggagaat ccctggaagt gctcgagcgg ggagcctaca ctcaagtcat ctttcttgcc 2640

cgcaacaaca ccatcgtgaa cgaattggtc cgcgtgacct ccgagggggc cggactccag 2700

ctgcaaaaag tgaccgtgct gggggtggca accgccccgc aacaagtgtt gtctaacgga 2760

gtgccggtgt ccaacttcac ctactcccct gataccaaag ttctagatat ttgcgtgagc 2820

ctgctgatgg gagaacagtt cctggtgtcc tggtgctga 2859

<210> 7

<211> 2859

<212> DNA

<213> 人工序列

<220>

<223> GAA密码子优化的2 (GAA21)

<400> 7

atgggagtta gacaccctcc atgtagccac agactgctgg ccgtgtgtgc tctggtgtct 60

ctggctacag ctgccctgct gggacatatc ctgctgcacg acttcttact agttcccaga 120

gagctgtccg gcagcagccc tgtgctggaa gaaacacacc ctgcacatca gcagggcgcc 180

tctagacctg gacctagaga tgctcaggcc catcctggca gacctagagc tgtgcccaca 240

cagtgtgacg tgccacctaa cagcagattc gactgcgccc ctgacaaggc catcacacaa 300

gagcagtgtg aagccagagg ctgctgctac atccctgcca aacaaggact gcagggcgct 360

cagatgggac agccctggtg cttcttccca ccatcttacc ccagctacaa gctggaaaac 420

ctgagcagca gcgagatggg ctacaccgcc acactgacca gaaccacacc tacattcttc 480

ccgaaggaca tcctgacact gcggctggac gtgatgatgg aaaccgagaa ccggctgcac 540

ttcaccatca aggaccccgc caatcggaga tacgaggtgc cactggaaac ccctcacgtg 600

cactctagag ccccatctcc actgtacagc gtggaattca gcgaggaacc cttcggcgtg 660

atcgtgcgga gacagctgga tggaagagtg ctgctgaaca ccacagtggc ccctctgttc 720

ttcgccgacc agtttctgca gctgtccacc agcctgccta gccagtatat cacaggcctg 780

gccgagcacc tgtctccact gatgctgtct accagctgga cccggatcac cctgtggaac 840

agggatcttg ctcctacacc tggcgccaac ctgtacggct ctcacccttt ttatctggcc 900

ctggaagatg gcggatctgc ccacggtgtc tttctgctga actccaacgc catggacgtg 960

gtgctgcagc catctcctgc tctgtcttgg agaagcacag gcggcatcct ggacgtgtac 1020

atctttctgg gccccgagcc taagagcgtg gtgcagcagt atctggacgt cgtgggctac 1080

cccttcatgc ctccttattg gggcctgggc ttccacctgt gcagatgggg atacagcagc 1140

accgccatca ccagacaggt ggtggaaaac atgacccggg ctcacttccc actggatgtg 1200

cagtggaacg acctggacta catggacagc agacgggact tcaccttcaa caaggacggc 1260

ttcagagact tccccgccat ggtgcaagaa ctgcaccaag gcggcagacg gtacatgatg 1320

atcgtggatc cagccatcag ctctagcggc cctgccggct cttacagacc ttacgatgag 1380

ggcctgagaa gaggcgtgtt catcaccaac gagacaggcc agcctctgat cggcaaagtg 1440

tggcctggca gcacagcctt tccagacttc acaaacccca ccgctctggc ttggtgggaa 1500

gatatggtgg ccgagtttca cgatcaggtg cccttcgacg gcatgtggat cgacatgaac 1560

gagcccagca acttcatccg gggcagcgag gatggctgcc ccaacaacga actggaaaat 1620

cctccttacg tgcccggcgt tgtcggcgga acacttcagg ccgctacaat ctgtgccagc 1680

agccaccagt tcctcagcac ccactacaac ctgcacaatc tgtatggcct gaccgaggcc 1740

attgccagcc atagagccct ggttaaggcc aggggcacca gacctttcgt gatcagcaga 1800

agcaccttcg ccggccacgg cagatatgcc ggacattgga caggcgacgt gtggtctagt 1860

tgggagcagc tggctagcag cgtgccagag atcctgcagt tcaatctgct gggcgtgcca 1920

ctcgtgggag ccgatgtttg tggcttcctg ggcaacacct ccgaggaact gtgtgtgcgt 1980

tggacacagc tgggcgcctt ctatcccttc atgagaaacc acaacagcct tctcagcctg 2040

ccacaagagc cctacagctt ctctgagcct gcacagcagg ccatgagaaa ggccctgact 2100

ctgagatacg ctctgctgcc ccacctgtac accctgtttc accaggctca tgtggccggg 2160

gagacagtgg ctagacctct gttcctggaa ttccccaagg acagctccac ctggaccgtg 2220

gatcatcagc tgctgtgggg agaagccctg ctcatcacac ctgttctgca ggccggaaag 2280

gccgaagtga ccggctattt tcctctcggc acttggtacg acctgcagac cgtgcctgtt 2340

gaggctctgg gatctcttcc tccacctcct gccgctccta gagagcctgc cattcactct 2400

gaaggccagt gggttaccct gcctgctcct ctggacacca tcaacgtgca cctgagagct 2460

ggctacatca tccctctgca aggccctggc ctgacaacca ccgaatctag acagcagccc 2520

atggctctgg ccgtggcttt gacaaaaggc ggagaggcta gaggcgagct gttctgggat 2580

gatggcgaga gcctggaagt gctggaacgg ggcgcttata cccaagtgat cttcctggcc 2640

agaaacaaca ccatcgtgaa cgaactcgtg cgcgtgacca gtgaaggtgc tggactgcaa 2700

ctgcagaaag tgaccgtgct cggagtggcc acagcacctc agcaggttct gtctaatggc 2760

gtgcccgtgt ccaacttcac atacagcccc gacaccaagg tcctggacat ctgtgtgtca 2820

ctgctgatgg gcgagcagtt cctggtgtcc tggtgttga 2859

<210> 8

<211> 952

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(952)

<223> 酸性α-葡糖苷酶 (GAA)

<400> 8

Met Gly Val Arg His Pro Pro Cys Ser His Arg Leu Leu Ala Val Cys

1 5 10 15

Ala Leu Val Ser Leu Ala Thr Ala Ala Leu Leu Gly His Ile Leu Leu

20 25 30

His Asp Phe Leu Leu Val Pro Arg Glu Leu Ser Gly Ser Ser Pro Val

35 40 45

Leu Glu Glu Thr His Pro Ala His Gln Gln Gly Ala Ser Arg Pro Gly

50 55 60

Pro Arg Asp Ala Gln Ala His Pro Gly Arg Pro Arg Ala Val Pro Thr

65 70 75 80

Gln Cys Asp Val Pro Pro Asn Ser Arg Phe Asp Cys Ala Pro Asp Lys

85 90 95

Ala Ile Thr Gln Glu Gln Cys Glu Ala Arg Gly Cys Cys Tyr Ile Pro

100 105 110

Ala Lys Gln Gly Leu Gln Gly Ala Gln Met Gly Gln Pro Trp Cys Phe

115 120 125

Phe Pro Pro Ser Tyr Pro Ser Tyr Lys Leu Glu Asn Leu Ser Ser Ser

130 135 140

Glu Met Gly Tyr Thr Ala Thr Leu Thr Arg Thr Thr Pro Thr Phe Phe

145 150 155 160

Pro Lys Asp Ile Leu Thr Leu Arg Leu Asp Val Met Met Glu Thr Glu

165 170 175

Asn Arg Leu His Phe Thr Ile Lys Asp Pro Ala Asn Arg Arg Tyr Glu

180 185 190

Val Pro Leu Glu Thr Pro His Val His Ser Arg Ala Pro Ser Pro Leu

195 200 205

Tyr Ser Val Glu Phe Ser Glu Glu Pro Phe Gly Val Ile Val Arg Arg

210 215 220

Gln Leu Asp Gly Arg Val Leu Leu Asn Thr Thr Val Ala Pro Leu Phe

225 230 235 240

Phe Ala Asp Gln Phe Leu Gln Leu Ser Thr Ser Leu Pro Ser Gln Tyr

245 250 255

Ile Thr Gly Leu Ala Glu His Leu Ser Pro Leu Met Leu Ser Thr Ser

260 265 270

Trp Thr Arg Ile Thr Leu Trp Asn Arg Asp Leu Ala Pro Thr Pro Gly

275 280 285

Ala Asn Leu Tyr Gly Ser His Pro Phe Tyr Leu Ala Leu Glu Asp Gly

290 295 300

Gly Ser Ala His Gly Val Phe Leu Leu Asn Ser Asn Ala Met Asp Val

305 310 315 320

Val Leu Gln Pro Ser Pro Ala Leu Ser Trp Arg Ser Thr Gly Gly Ile

325 330 335

Leu Asp Val Tyr Ile Phe Leu Gly Pro Glu Pro Lys Ser Val Val Gln

340 345 350

Gln Tyr Leu Asp Val Val Gly Tyr Pro Phe Met Pro Pro Tyr Trp Gly

355 360 365

Leu Gly Phe His Leu Cys Arg Trp Gly Tyr Ser Ser Thr Ala Ile Thr

370 375 380

Arg Gln Val Val Glu Asn Met Thr Arg Ala His Phe Pro Leu Asp Val

385 390 395 400

Gln Trp Asn Asp Leu Asp Tyr Met Asp Ser Arg Arg Asp Phe Thr Phe

405 410 415

Asn Lys Asp Gly Phe Arg Asp Phe Pro Ala Met Val Gln Glu Leu His

420 425 430

Gln Gly Gly Arg Arg Tyr Met Met Ile Val Asp Pro Ala Ile Ser Ser

435 440 445

Ser Gly Pro Ala Gly Ser Tyr Arg Pro Tyr Asp Glu Gly Leu Arg Arg

450 455 460

Gly Val Phe Ile Thr Asn Glu Thr Gly Gln Pro Leu Ile Gly Lys Val

465 470 475 480

Trp Pro Gly Ser Thr Ala Phe Pro Asp Phe Thr Asn Pro Thr Ala Leu

485 490 495

Ala Trp Trp Glu Asp Met Val Ala Glu Phe His Asp Gln Val Pro Phe

500 505 510

Asp Gly Met Trp Ile Asp Met Asn Glu Pro Ser Asn Phe Ile Arg Gly

515 520 525

Ser Glu Asp Gly Cys Pro Asn Asn Glu Leu Glu Asn Pro Pro Tyr Val

530 535 540

Pro Gly Val Val Gly Gly Thr Leu Gln Ala Ala Thr Ile Cys Ala Ser

545 550 555 560

Ser His Gln Phe Leu Ser Thr His Tyr Asn Leu His Asn Leu Tyr Gly

565 570 575

Leu Thr Glu Ala Ile Ala Ser His Arg Ala Leu Val Lys Ala Arg Gly

580 585 590

Thr Arg Pro Phe Val Ile Ser Arg Ser Thr Phe Ala Gly His Gly Arg

595 600 605

Tyr Ala Gly His Trp Thr Gly Asp Val Trp Ser Ser Trp Glu Gln Leu

610 615 620

Ala Ser Ser Val Pro Glu Ile Leu Gln Phe Asn Leu Leu Gly Val Pro

625 630 635 640

Leu Val Gly Ala Asp Val Cys Gly Phe Leu Gly Asn Thr Ser Glu Glu

645 650 655

Leu Cys Val Arg Trp Thr Gln Leu Gly Ala Phe Tyr Pro Phe Met Arg

660 665 670

Asn His Asn Ser Leu Leu Ser Leu Pro Gln Glu Pro Tyr Ser Phe Ser

675 680 685

Glu Pro Ala Gln Gln Ala Met Arg Lys Ala Leu Thr Leu Arg Tyr Ala

690 695 700

Leu Leu Pro His Leu Tyr Thr Leu Phe His Gln Ala His Val Ala Gly

705 710 715 720

Glu Thr Val Ala Arg Pro Leu Phe Leu Glu Phe Pro Lys Asp Ser Ser

725 730 735

Thr Trp Thr Val Asp His Gln Leu Leu Trp Gly Glu Ala Leu Leu Ile

740 745 750

Thr Pro Val Leu Gln Ala Gly Lys Ala Glu Val Thr Gly Tyr Phe Pro

755 760 765

Leu Gly Thr Trp Tyr Asp Leu Gln Thr Val Pro Val Glu Ala Leu Gly

770 775 780

Ser Leu Pro Pro Pro Pro Ala Ala Pro Arg Glu Pro Ala Ile His Ser

785 790 795 800

Glu Gly Gln Trp Val Thr Leu Pro Ala Pro Leu Asp Thr Ile Asn Val

805 810 815

His Leu Arg Ala Gly Tyr Ile Ile Pro Leu Gln Gly Pro Gly Leu Thr

820 825 830

Thr Thr Glu Ser Arg Gln Gln Pro Met Ala Leu Ala Val Ala Leu Thr

835 840 845

Lys Gly Gly Glu Ala Arg Gly Glu Leu Phe Trp Asp Asp Gly Glu Ser

850 855 860

Leu Glu Val Leu Glu Arg Gly Ala Tyr Thr Gln Val Ile Phe Leu Ala

865 870 875 880

Arg Asn Asn Thr Ile Val Asn Glu Leu Val Arg Val Thr Ser Glu Gly

885 890 895

Ala Gly Leu Gln Leu Gln Lys Val Thr Val Leu Gly Val Ala Thr Ala

900 905 910

Pro Gln Gln Val Leu Ser Asn Gly Val Pro Val Ser Asn Phe Thr Tyr

915 920 925

Ser Pro Asp Thr Lys Val Leu Asp Ile Cys Val Ser Leu Leu Met Gly

930 935 940

Glu Gln Phe Leu Val Ser Trp Cys

945 950

<210> 9

<211> 1290

<212> DNA

<213> 人工序列

<220>

<223> GLA

<400> 9

atgcagctga ggaacccaga actacatctg ggctgcgcgc ttgcgcttcg cttcctggcc 60

ctcgtttcct gggacatccc tggggctaga gcactggaca atggattggc aaggacgcct 120

accatgggct ggctgcactg ggagcgcttc atgtgcaacc ttgactgcca ggaagagcca 180

gattcctgca tcagtgagaa gctcttcatg gagatggcag agctcatggt ctcagaaggc 240

tggaaggatg caggttatga gtacctctgc attgatgact gttggatggc tccccaaaga 300

gattcagaag gcagacttca ggcagaccct cagcgctttc ctcatgggat tcgccagcta 360

gctaattatg ttcacagcaa aggactgaag ctagggattt atgcagatgt tggaaataaa 420

acctgcgcag gcttccctgg gagttttgga tactacgaca ttgatgccca gacctttgct 480

gactggggag tagatctgct aaaatttgat ggttgttact gtgacagttt ggaaaatttg 540

gcagatggtt ataagcacat gtccttggcc ctgaatagga ctggcagaag cattgtgtac 600

tcctgtgagt ggcctcttta tatgtggccc tttcaaaagc ccaattatac agaaatccga 660

cagtactgca atcactggcg aaattttgct gacattgatg attcctggaa aagtataaag 720

agtatcttgg actggacatc ttttaaccag gagagaattg ttgatgttgc tggaccaggg 780

ggttggaatg acccagatat gttagtgatt ggcaactttg gcctcagctg gaatcagcaa 840

gtaactcaga tggccctctg ggctatcatg gctgctcctt tattcatgtc taatgacctc 900

cgacacatca gccctcaagc caaagctctc cttcaggata aggacgtaat tgccatcaat 960

caggacccct tgggcaagca agggtaccag cttagacagg gagacaactt tgaagtgtgg 1020

gaacgacctc tctcaggctt agcctgggct gtagctatga taaaccggca ggagattggt 1080

ggacctcgct cttataccat cgcagttgct tccctgggta aaggagtggc ctgtaatcct 1140

gcctgcttca tcacacagct cctccctgtg aaaaggaagc tagggttcta tgaatggact 1200

tcaaggttaa gaagtcacat aaatcccaca ggcactgttt tgcttcagct agaaaataca 1260

atgcagatgt cattaaaaga cttactttaa 1290

<210> 10

<211> 1290

<212> DNA

<213> 人工序列

<220>

<223> GLA密码子优化的

<400> 10

atgcagctga gaaatcctga actgcacctg ggctgtgccc tggctctgag atttctggct 60

ctggtgtcct gggacattcc tggcgctaga gccctggata atggcctggc cagaacacct 120

acaatgggct ggctgcactg ggagagattc atgtgcaacc tggactgcca agaggaaccc 180

gacagctgca tcagcgagaa gctgttcatg gaaatggccg agctgatggt gtccgaaggc 240

tggaaggatg ccggctacga gtacctgtgc atcgacgatt gctggatggc ccctcagaga 300

gattctgagg gcagactgca ggccgatcct cagagatttc ctcacggaat ccggcagctg 360

gccaactacg tgcactctaa gggactgaag ctgggcatct acgccgacgt gggcaacaag 420

acatgtgccg gctttccagg cagcttcggc tactacgata tcgacgccca gacctttgcc 480

gattggggcg tcgacctgct gaagttcgat ggctgctact gcgacagcct ggaaaacctg 540

gccgacggct acaaacacat gtctctggcc ctgaaccgga ccggcagatc tatcgtgtac 600

tcttgcgagt ggcccctgta catgtggccc ttccagaagc ctaactacac cgagatcaga 660

cagtactgca accactggcg gaacttcgcc gacatcgatg acagctggaa gtccatcaag 720

agcatcctgg actggaccag cttcaatcaa gagcggatcg tggatgtggc tggcccaggc 780

ggatggaacg atcctgatat gctggtcatc ggcaacttcg gcctgagctg gaatcagcaa 840

gtgacccaga tggccctgtg ggccattatg gccgctcctc tgttcatgag caacgacctg 900

agacacatca gccctcaggc caaggctctg ctgcaggata aggacgtgat cgccatcaac 960

caggatcctc tgggcaagca gggctatcag ctgagacagg gcgacaattt cgaagtgtgg 1020

gaaagacctc tgagcggcct ggcttgggcc gtcgccatga tcaatagaca agagatcggc 1080

ggaccccggt cctatacaat tgccgtggct tctctcggaa aaggcgtggc ctgcaatcct 1140

gcctgcttta tcacacagct gctccccgtg aagagaaagc tgggctttta cgagtggacc 1200

agcagactga gatcccacat caaccccaca ggcactgttc tgctgcaact ggaaaacaca 1260

atgcagatga gcctgaagga cctgctgtag 1290

<210> 11

<211> 429

<212> PRT

<213> 人工序列

<220>

<223> GLA

<400> 11

Met Gln Leu Arg Asn Pro Glu Leu His Leu Gly Cys Ala Leu Ala Leu

1 5 10 15

Arg Phe Leu Ala Leu Val Ser Trp Asp Ile Pro Gly Ala Arg Ala Leu

20 25 30

Asp Asn Gly Leu Ala Arg Thr Pro Thr Met Gly Trp Leu His Trp Glu

35 40 45

Arg Phe Met Cys Asn Leu Asp Cys Gln Glu Glu Pro Asp Ser Cys Ile

50 55 60

Ser Glu Lys Leu Phe Met Glu Met Ala Glu Leu Met Val Ser Glu Gly

65 70 75 80

Trp Lys Asp Ala Gly Tyr Glu Tyr Leu Cys Ile Asp Asp Cys Trp Met

85 90 95

Ala Pro Gln Arg Asp Ser Glu Gly Arg Leu Gln Ala Asp Pro Gln Arg

100 105 110

Phe Pro His Gly Ile Arg Gln Leu Ala Asn Tyr Val His Ser Lys Gly

115 120 125

Leu Lys Leu Gly Ile Tyr Ala Asp Val Gly Asn Lys Thr Cys Ala Gly

130 135 140

Phe Pro Gly Ser Phe Gly Tyr Tyr Asp Ile Asp Ala Gln Thr Phe Ala

145 150 155 160

Asp Trp Gly Val Asp Leu Leu Lys Phe Asp Gly Cys Tyr Cys Asp Ser

165 170 175

Leu Glu Asn Leu Ala Asp Gly Tyr Lys His Met Ser Leu Ala Leu Asn

180 185 190

Arg Thr Gly Arg Ser Ile Val Tyr Ser Cys Glu Trp Pro Leu Tyr Met

195 200 205

Trp Pro Phe Gln Lys Pro Asn Tyr Thr Glu Ile Arg Gln Tyr Cys Asn

210 215 220

His Trp Arg Asn Phe Ala Asp Ile Asp Asp Ser Trp Lys Ser Ile Lys

225 230 235 240

Ser Ile Leu Asp Trp Thr Ser Phe Asn Gln Glu Arg Ile Val Asp Val

245 250 255

Ala Gly Pro Gly Gly Trp Asn Asp Pro Asp Met Leu Val Ile Gly Asn

260 265 270

Phe Gly Leu Ser Trp Asn Gln Gln Val Thr Gln Met Ala Leu Trp Ala

275 280 285

Ile Met Ala Ala Pro Leu Phe Met Ser Asn Asp Leu Arg His Ile Ser

290 295 300

Pro Gln Ala Lys Ala Leu Leu Gln Asp Lys Asp Val Ile Ala Ile Asn

305 310 315 320

Gln Asp Pro Leu Gly Lys Gln Gly Tyr Gln Leu Arg Gln Gly Asp Asn

325 330 335

Phe Glu Val Trp Glu Arg Pro Leu Ser Gly Leu Ala Trp Ala Val Ala

340 345 350

Met Ile Asn Arg Gln Glu Ile Gly Gly Pro Arg Ser Tyr Thr Ile Ala

355 360 365

Val Ala Ser Leu Gly Lys Gly Val Ala Cys Asn Pro Ala Cys Phe Ile

370 375 380

Thr Gln Leu Leu Pro Val Lys Arg Lys Leu Gly Phe Tyr Glu Trp Thr

385 390 395 400

Ser Arg Leu Arg Ser His Ile Asn Pro Thr Gly Thr Val Leu Leu Gln

405 410 415

Leu Glu Asn Thr Met Gln Met Ser Leu Lys Asp Leu Leu

420 425

<210> 12

<211> 1317

<212> DNA

<213> 人工序列

<220>

<223> CLN3

<400> 12

atgggaggct gtgcaggctc gcggcggcgc ttttcggatt ccgaggggga ggagaccgtc 60

ccggagcccc ggctccctct gttggaccat cagggcgcgc attggaagaa cgcggtgggc 120

ttctggctgc tgggcctttg caacaacttc tcttatgtgg tgatgctgag tgccgcccac 180

gacatcctta gccacaagag gacatcggga aaccagagcc atgtggaccc aggcccaacg 240

ccgatccccc acaacagctc atcacgattt gactgcaact ctgtctctac ggctgctgtg 300

ctcctggcgg acatcctccc cacactcgtc atcaaattgt tggctcctct tggccttcac 360

ctgctgccct acagcccccg ggttctcgtc agtgggattt gtgctgctgg aagcttcgtc 420

ctggttgcct tttctcattc tgtggggacc agcctgtgtg gtgtggtctt cgctagcatc 480

tcatcaggcc ttggggaggt caccttcctc tccctcactg ccttctaccc cagggccgtg 540

atctcctggt ggtcctcagg gactggggga gctgggctgc tgggggccct gtcctacctg 600

ggcctcaccc aggccggcct ctcccctcag cagaccctgc tgtccatgct gggtatccct 660

gccctgctgc tggccagcta tttcttgttg ctcacatctc ctgaggccca ggaccctgga 720

ggggaagaag aagcagagag cgcagcccgg cagcccctca taagaaccga ggccccggag 780

tcgaagccag gctccagctc cagcctctcc cttcgggaaa ggtggacagt gttcaagggt 840

ctgctgtggt acattgttcc cttggtcgta gtttactttg ccgagtattt cattaaccag 900

ggactttttg aactcctctt tttctggaac acttccctga gtcacgctca gcaataccgc 960

tggtaccaga tgctgtacca ggctggcgtc tttgcctccc gctcttctct ccgctgctgt 1020

cgcatccgtt tcacctgggc cctggccctg ctgcagtgcc tcaacctggt gttcctgctg 1080

gcagacgtgt ggttcggctt tctgccaagc atctacctcg tcttcctgat cattctgtat 1140

gaggggctcc tgggaggcgc agcctacgtg aacaccttcc acaacatcgc cctggagacc 1200

agtgatgagc accgggagtt tgcaatggcg gccacctgca tctctgacac actggggatc 1260

tccctgtcgg ggctcctggc tttgcctctg catgacttcc tctgccagct ctcctga 1317

<210> 13

<211> 1318

<212> DNA

<213> 人工序列

<220>

<223> CLN3密码子优化的

<400> 13

atgggaggat gtgctgggtc aagaagacgg tttagcgatt ccgaaggaga ggagactgtg 60

cctgagccaa gactgcccct gctggatcac cagggagcac actggaagaa cgcagtggga 120

ttctggctgc tgggcctgtg caacaacttc agctacgtgg tcatgctgtc cgccgcccac 180

gacatcctgt cccacaagcg gacctccggc aatcagtctc acgtggaccc cggccctaca 240

ccaatccccc acaacagcag cagccggttc gactgtaatt ccgtgtctac cgcagccgtg 300

ctgctggcag acatcctgcc caccctggtc atcaagctgc tggcaccact gggcctgcac 360

ctgctgcctt attctccaag ggtgctggtg agcggcatct gcgcagcagg cagcttcgtg 420

ctggtggcct ttagccactc cgtgggcacc tctctgtgcg gagtggtgtt tgcaagcatc 480

agctccggcc tgggagaggt gaccttcctg agcctgacag ccttttaccc tcgcgccgtg 540

atctcctggt ggtctagcgg cacaggagga gcaggcctgc tgggcgccct gtcctatctg 600

ggcctgaccc aggcaggcct gtccccacag cagacactgc tgtctatgct gggcatccct 660

gccctgctgc tggcaagcta cttcctgctg ctgacctccc cagaggcaca ggaccccgga 720

ggagaggagg aggccgagag cgccgcaagg cagccactga tcaggaccga ggcaccagag 780

tccaagcctg gctcctctag ctccctgtct ctgcgggaga gatggacagt gttcaagggc 840

ctgctgtggt acatcgtgcc cctggtggtg gtgtacttcg ccgagtactt catcaaccag 900

ggcctgtttg agctgctgtt cttttggaat acctctctga gccacgccca gcagtaccgg 960

tggtatcaga tgctgtatca ggcaggcgtg ttcgcctccc ggtctagcct gagatgctgt 1020

cggatcagat tcacctgggc actggccctg ctgcagtgcc tgaacctggt gttcctgctg 1080

gccgacgtgt ggttcggctt tctgccctct atctacctgg tgtttctgat catcctgtat 1140

gagggcctgc tgggaggagc agcctatgtg aacaccttcc acaatatcgc cctggagaca 1200

tctgacgagc acagagagtt tgctatggcc gccacctgta tcagcgatac actgggcatc 1260

tctctgagcg gactgctggc tctgcctctg catgactttc tgtgccagct gagttaat 1318

<210> 14

<211> 438

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(438)

<223> 蜡样质脂褐质沉积症神经元蛋白3 (CLN3)

<400> 14

Met Gly Gly Cys Ala Gly Ser Arg Arg Arg Phe Ser Asp Ser Glu Gly

1 5 10 15

Glu Glu Thr Val Pro Glu Pro Arg Leu Pro Leu Leu Asp His Gln Gly

20 25 30

Ala His Trp Lys Asn Ala Val Gly Phe Trp Leu Leu Gly Leu Cys Asn

35 40 45

Asn Phe Ser Tyr Val Val Met Leu Ser Ala Ala His Asp Ile Leu Ser

50 55 60

His Lys Arg Thr Ser Gly Asn Gln Ser His Val Asp Pro Gly Pro Thr

65 70 75 80

Pro Ile Pro His Asn Ser Ser Ser Arg Phe Asp Cys Asn Ser Val Ser

85 90 95

Thr Ala Ala Val Leu Leu Ala Asp Ile Leu Pro Thr Leu Val Ile Lys

100 105 110

Leu Leu Ala Pro Leu Gly Leu His Leu Leu Pro Tyr Ser Pro Arg Val

115 120 125

Leu Val Ser Gly Ile Cys Ala Ala Gly Ser Phe Val Leu Val Ala Phe

130 135 140

Ser His Ser Val Gly Thr Ser Leu Cys Gly Val Val Phe Ala Ser Ile

145 150 155 160

Ser Ser Gly Leu Gly Glu Val Thr Phe Leu Ser Leu Thr Ala Phe Tyr

165 170 175

Pro Arg Ala Val Ile Ser Trp Trp Ser Ser Gly Thr Gly Gly Ala Gly

180 185 190

Leu Leu Gly Ala Leu Ser Tyr Leu Gly Leu Thr Gln Ala Gly Leu Ser

195 200 205

Pro Gln Gln Thr Leu Leu Ser Met Leu Gly Ile Pro Ala Leu Leu Leu

210 215 220

Ala Ser Tyr Phe Leu Leu Leu Thr Ser Pro Glu Ala Gln Asp Pro Gly

225 230 235 240

Gly Glu Glu Glu Ala Glu Ser Ala Ala Arg Gln Pro Leu Ile Arg Thr

245 250 255

Glu Ala Pro Glu Ser Lys Pro Gly Ser Ser Ser Ser Leu Ser Leu Arg

260 265 270

Glu Arg Trp Thr Val Phe Lys Gly Leu Leu Trp Tyr Ile Val Pro Leu

275 280 285

Val Val Val Tyr Phe Ala Glu Tyr Phe Ile Asn Gln Gly Leu Phe Glu

290 295 300

Leu Leu Phe Phe Trp Asn Thr Ser Leu Ser His Ala Gln Gln Tyr Arg

305 310 315 320

Trp Tyr Gln Met Leu Tyr Gln Ala Gly Val Phe Ala Ser Arg Ser Ser

325 330 335

Leu Arg Cys Cys Arg Ile Arg Phe Thr Trp Ala Leu Ala Leu Leu Gln

340 345 350

Cys Leu Asn Leu Val Phe Leu Leu Ala Asp Val Trp Phe Gly Phe Leu

355 360 365

Pro Ser Ile Tyr Leu Val Phe Leu Ile Ile Leu Tyr Glu Gly Leu Leu

370 375 380

Gly Gly Ala Ala Tyr Val Asn Thr Phe His Asn Ile Ala Leu Glu Thr

385 390 395 400

Ser Asp Glu His Arg Glu Phe Ala Met Ala Ala Thr Cys Ile Ser Asp

405 410 415

Thr Leu Gly Ile Ser Leu Ser Gly Leu Leu Ala Leu Pro Leu His Asp

420 425 430

Phe Leu Cys Gln Leu Ser

435

<210> 15

<211> 2211

<212> DNA

<213> 人工序列

<220>

<223> AAV204 VP1

<400> 15

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acttgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaac gtccggtaga gcagtcacca caagagccag actcctcctc gggcatcggc 480

aagacaggcc agcagcccgc taaaaagaga ctcaattttg gtcagactgg cgactcagag 540

tcagtccccg acccacaacc tctcggagaa cctccagcaa cccccgctgc tgtgggacct 600

actacaatgg cttcaggcgg tggcgcacca atggcggaca ataacgaagg cgccgacgga 660

gtgggtaatg cctcaggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc 720

accaccagca cccgaacatg ggccttgccc acctataaca accacctcta caagcaaatc 780

tccagtgctt caacgggggc cagcaacgac aaccactact tcggctacag caccccctgg 840

gggtattttg atttcaacag attccactgc catttctcac cacgtgactg gcagcgactc 900

atcaacaaca attggggatt ccggcccaag agactcaact tcaagctctt caacatccaa 960

gtcaaggagg tcacgacgaa tgatggcgtc acgaccatcg ctaataacct taccagcacg 1020

gttcaagtct tctcggactc ggagtaccag ttgccgtacg tcctcggctc tgcgcaccag 1080

ggctgcctcc ctccgttccc ggcggacgtg ttcatgattc cgcagtacgg ctacctaacg 1140

ctcaacaatg gcagccaggc agtgggacgg tcatcctttt actgcctgga atatttccca 1200

tcgcagatgc tgagaacggg caataacttt accttcagct acaccttcga ggacgtgcct 1260

ttccacagca gctacgcgca cagccagagc ctggaccggc tgatgaatcc tctcatcgac 1320

cagtacctgt attacctgaa cagaactcag aatcagtccg gaagtgccca aaacaaggac 1380

ttgctgttta gccgggggtc tccagctggc atgtctgttc agcccaaaaa ctggctacct 1440

ggaccctgtt accggcagca gcgcgtttct aaaacaaaaa cagacaacaa caacagcaac 1500

tttacctgga caggtgcttc aaaatataac cttaatgggc gtgaatctat aatcaaccct 1560

ggcactgcta tggcctcaca caaagacgac aaagacaagt tctttcccat gagcggtgtc 1620

atgatttttg gaaaggagag cgccggagct tcaaacactg cattggacaa tgtcatgatc 1680

acagacgaag aggaaatcaa agccactaac cccgtggcca ccgaaagatt tgggactgtg 1740

gcagtcaatc tccagaacag cagcacagac cctgcgaccg gagatgtgca tgttatggga 1800

gccttacctg gaatggtgtg gcaagacaga gacgtatacc tgcagggtcc tatttgggcc 1860

aaaattcctc acacggatgg acactttcac ccgtctcctc tcatgggcgg ctttggactt 1920

aagcacccgc ctcctcagat cctcatcaaa aacacgcctg ttcctgcgaa tcctccggca 1980

gagttttcgg ctacaaagtt tgcttcattc atcacccagt attccacagg acaagtgagc 2040

gtggagattg aatgggagct gcagaaagaa aacagcaaac gctggaatcc cgaagtgcag 2100

tatacatcta actatgcaaa atctgccaac gttgatttca ctgtagacaa caatggactt 2160

tatactgagc ctcgccccat tggcacccgt tacctcaccc gtcccctgta a 2211

<210> 16

<211> 1605

<212> DNA

<213> 人工序列

<220>

<223> AAV204 VP3

<400> 16

atggcttcag gcggtggcgc accaatggcg gacaataacg aaggcgccga cggagtgggt 60

aatgcctcag gaaattggca ttgcgattcc acatggctgg gcgacagagt catcaccacc 120

agcacccgaa catgggcctt gcccacctat aacaaccacc tctacaagca aatctccagt 180

gcttcaacgg gggccagcaa cgacaaccac tacttcggct acagcacccc ctgggggtat 240

tttgatttca acagattcca ctgccatttc tcaccacgtg actggcagcg actcatcaac 300

aacaattggg gattccggcc caagagactc aacttcaagc tcttcaacat ccaagtcaag 360

gaggtcacga cgaatgatgg cgtcacgacc atcgctaata accttaccag cacggttcaa 420

gtcttctcgg actcggagta ccagttgccg tacgtcctcg gctctgcgca ccagggctgc 480

ctccctccgt tcccggcgga cgtgttcatg attccgcagt acggctacct aacgctcaac 540

aatggcagcc aggcagtggg acggtcatcc ttttactgcc tggaatattt cccatcgcag 600

atgctgagaa cgggcaataa ctttaccttc agctacacct tcgaggacgt gcctttccac 660

agcagctacg cgcacagcca gagcctggac cggctgatga atcctctcat cgaccagtac 720

ctgtattacc tgaacagaac tcagaatcag tccggaagtg cccaaaacaa ggacttgctg 780

tttagccggg ggtctccagc tggcatgtct gttcagccca aaaactggct acctggaccc 840

tgttaccggc agcagcgcgt ttctaaaaca aaaacagaca acaacaacag caactttacc 900

tggacaggtg cttcaaaata taaccttaat gggcgtgaat ctataatcaa ccctggcact 960

gctatggcct cacacaaaga cgacaaagac aagttctttc ccatgagcgg tgtcatgatt 1020

tttggaaagg agagcgccgg agcttcaaac actgcattgg acaatgtcat gatcacagac 1080

gaagaggaaa tcaaagccac taaccccgtg gccaccgaaa gatttgggac tgtggcagtc 1140

aatctccaga acagcagcac agaccctgcg accggagatg tgcatgttat gggagcctta 1200

cctggaatgg tgtggcaaga cagagacgta tacctgcagg gtcctatttg ggccaaaatt 1260

cctcacacgg atggacactt tcacccgtct cctctcatgg gcggctttgg acttaagcac 1320

ccgcctcctc agatcctcat caaaaacacg cctgttcctg cgaatcctcc ggcagagttt 1380

tcggctacaa agtttgcttc attcatcacc cagtattcca caggacaagt gagcgtggag 1440

attgaatggg agctgcagaa agaaaacagc aaacgctgga atcccgaagt gcagtataca 1500

tctaactatg caaaatctgc caacgttgat ttcactgtag acaacaatgg actttatact 1560

gagcctcgcc ccattggcac ccgttacctc acccgtcccc tgtaa 1605

<210> 17

<211> 534

<212> PRT

<213> 人工序列

<220>

<223> AAV204 VP3

<400> 17

Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly

50 55 60

Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr

65 70 75 80

Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln

85 90 95

Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe

100 105 110

Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Thr Asn Asp Gly Val

115 120 125

Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Ser Asp

130 135 140

Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys

145 150 155 160

Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr

165 170 175

Leu Thr Leu Asn Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr

180 185 190

Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe

195 200 205

Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala

210 215 220

His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr

225 230 235 240

Leu Tyr Tyr Leu Asn Arg Thr Gln Asn Gln Ser Gly Ser Ala Gln Asn

245 250 255

Lys Asp Leu Leu Phe Ser Arg Gly Ser Pro Ala Gly Met Ser Val Gln

260 265 270

Pro Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser

275 280 285

Lys Thr Lys Thr Asp Asn Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala

290 295 300

Ser Lys Tyr Asn Leu Asn Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr

305 310 315 320

Ala Met Ala Ser His Lys Asp Asp Lys Asp Lys Phe Phe Pro Met Ser

325 330 335

Gly Val Met Ile Phe Gly Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala

340 345 350

Leu Asp Asn Val Met Ile Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn

355 360 365

Pro Val Ala Thr Glu Arg Phe Gly Thr Val Ala Val Asn Leu Gln Asn

370 375 380

Ser Ser Thr Asp Pro Ala Thr Gly Asp Val His Val Met Gly Ala Leu

385 390 395 400

Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile

405 410 415

Trp Ala Lys Ile Pro His Thr Asp Gly His Phe His Pro Ser Pro Leu

420 425 430

Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys

435 440 445

Asn Thr Pro Val Pro Ala Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys

450 455 460

Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu

465 470 475 480

Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu

485 490 495

Val Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr

500 505 510

Val Asp Asn Asn Gly Leu Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg

515 520 525

Tyr Leu Thr Arg Pro Leu

530

<210> 18

<211> 2208

<212> DNA

<213> 人工序列

<220>

<223> ITB102 214 (AAV214) VP1

<400> 18

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg cgctgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga accttttggt ctggttgagg aaggtgctaa gacggctcct 420

ggaaagaaac gtccggtaga gcagtcgcca caagagccag actcctcctc gggcatcggc 480

aagacaggcc agcagcccgc taaaaagaga ctcaattttg gtcagactgg cgactcagag 540

tcagtccccg acccacaacc tctcggagaa cctccagcaa cccccgctgc tgtgggacct 600

actacaatgg cttcaggcgg tggcgcacca atggcggaca ataacgaagg cgccgacgga 660

gtgggtaatg cctcaggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc 720

accaccagca cccgcacctg ggccttgccc acctacaata accacctcta caagcaaatc 780

tccagtgctt caacgggggc cagcaacgac aaccactact tcggctacag caccccctgg 840

gggtattttg acttcaacag attccactgc cacttttcac cacgtgactg gcaaagactc 900

atcaacaaca actggggatt ccgacccaag agactcaact tcaagctctt taacattcaa 960

gtcaaagagg ttacggacaa caatggagtc aagaccatcg ccaataacct taccagcacg 1020

gtccaggtct tcacggactc agactatcag ctcccgtacg tcctcggctc tgcgcaccag 1080

ggctgcctcc ctccgttccc ggcggacgtg ttcatgattc cgcagtacgg ctacctaacg 1140

ctcaacgacg gcagccaggc agtgggacgg tcatcctttt actgcctgga atatttccca 1200

tcgcagatgc tgagaacggg caacaacttt accttcagct acacctttga ggacgttcct 1260

ttccacagca gctacgctca cagccagagt ctggaccgtc tcatgaatcc tctgattgac 1320

cagtacctgt actacttgtc taagactatc aacggatccg gccagaatca gcagactctg 1380

aagttcagcc aaggtgggcc taatacaatg gccaatcagg caaagaactg gctgccagga 1440

ccctgttacc gccaacaacg cgtctcaacg acaaccgggc aaaacaacaa tagcaacttt 1500

gcctggactg ctgggaccaa ataccatctg aatggaagaa attcattgat gaatcctggc 1560

cccgctatgg catcccacaa agagggcgag gaccgttttt ttcccctgtc cgggtccctg 1620

atttttggca aacaaaatgc tgccagagac aatgcggatt acagcgatgt catgctcacc 1680

agcgaggaag aaatcaaaac cactaaccct gtggctacag aggaatacgg tatcgtggca 1740

gataacttgc agcagcaaaa cacggctcct caaattggaa ctgtcaacag ccagggggcc 1800

ttacccggta tggtctggca gaaccgggac gtgtacctgc agggtcccat ctgggccaag 1860

attcctcaca cggacggcaa cttccacccg tctccgctga tgggcggctt tggcctgaaa 1920

catcctccgc ctcagatcct gatcaagaac acgcctgtac ctgcggatcc tccgaccacc 1980

ttcaaccagt caaagctgaa ctctttcatc acgcaataca gcaccggaca ggtcagcgtg 2040

gaaattgaat gggagctgca gaaggaaaac agcaagcgct ggaaccccga gatccagtac 2100

acctccaact actacaaatc tacaagtgtg gactttgctg ttaatacaga aggcgtgtac 2160

tctgaacccc accccattgg cacccgttac ctcacccgtc ccctgtaa 2208

<210> 19

<211> 2211

<212> DNA

<213> 人工序列

<220>

<223> AAV214-A VP1

<400> 19

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg cgctgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga accttttggt ctggttgagg aaggtgctaa gacggctcct 420

ggaaagaaac gtccggtaga gcagtcgcca caagagccag actcctcctc gggcatcggc 480

aagacaggcc agcagcccgc taaaaagaga ctcaattttg gtcagactgg cgactcagag 540

tcagtccccg acccacaacc tctcggagaa cctccagcaa cccccgctgc tgtgggacct 600

actacaatgg cttcaggcgg tggcgcacca atggcggaca ataacgaagg cgccgacgga 660

gtgggtaatg cctcaggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc 720

accaccagca cccgcacctg ggccttgccc acctacaata accacctcta caagcaaatc 780

tccaacagca catctggagg atcttcaaat gacaacgcct acttcggcta cagcaccccc 840

tgggggtatt ttgacttcaa cagattccac tgccactttt caccacgtga ctggcaaaga 900

ctcatcaaca acaactgggg attccgaccc aagagactca acttcaagct ctttaacatt 960

caagtcaaag aggttacgga caacaatgga gtcaagacca tcgccaataa ccttaccagc 1020

acggtccagg tcttcacgga ctcagactat cagctcccgt acgtcctcgg ctctgcgcac 1080

cagggctgcc tccctccgtt cccggcggac gtgttcatga ttccgcagta cggctaccta 1140

acgctcaacg acggcagcca ggcagtggga cggtcatcct tttactgcct ggaatatttc 1200

ccatcgcaga tgctgagaac gggcaacaac tttaccttca gctacacctt tgaggacgtt 1260

cctttccaca gcagctacgc tcacagccag agtctggacc gtctcatgaa tcctctgatt 1320

gaccagtacc tgtactactt gtctaagact atcaacggat ccggccagaa tcagcagact 1380

ctgaagttca gccaaggtgg gcctaataca atggccaatc aggcaaagaa ctggctgcca 1440

ggaccctgtt accgccaaca acgcgtctca acgacaaccg ggcaaaacaa caatagcaac 1500

tttgcctgga ctgctgggac caaataccat ctgaatggaa gaaattcatt gatgaatcct 1560

ggccccgcta tggcatccca caaagagggc gaggaccgtt tttttcccct gtccgggtcc 1620

ctgatttttg gcaaacaaaa tgctgccaga gacaatgcgg attacagcga tgtcatgctc 1680

accagcgagg aagaaatcaa aaccactaac cctgtggcta cagaggaata cggtatcgtg 1740

gcagataact tgcagcagca aaacacggct cctcaaattg gaactgtcaa cagccagggg 1800

gccttacccg gtatggtctg gcagaaccgg gacgtgtacc tgcagggtcc catctgggcc 1860

aagattcctc acacggacgg caacttccac ccgtctccgc tgatgggcgg ctttggcctg 1920

aaacatcctc cgcctcagat cctgatcaag aacacgcctg tacctgcgga tcctccgacc 1980

accttcaacc agtcaaagct gaactctttc atcacgcaat acagcaccgg acaggtcagc 2040

gtggaaattg aatgggagct gcagaaggaa aacagcaagc gctggaaccc cgagatccag 2100

tacacctcca actactacaa atctacaagt gtggactttg ctgttaatac agaaggcgtg 2160

tactctgaac cccaccccat tggcacccgt tacctcaccc gtcccctgta a 2211

<210> 20

<211> 2211

<212> DNA

<213> 人工序列

<220>

<223> AAV214e VP1

<400> 20

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggatgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gaccggtaga gccatcaccc cagcgttctc cagactcctc tacgggcatc 480

ggcaagaaag gccaacagcc cgccagaaaa agactcaatt ttggtcagac tggcgactca 540

gagtcagtcc ccgacccaca acctctcgga gaacctccag caacccccgc tgctgtggga 600

cctactacaa tggcttcagg cggtggcgca ccaatggcag acaataacga aggcgccgac 660

ggagtgggta atgcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720

atcaccacca gcacccgcac ctgggccttg cccacctaca ataaccacct ctacaagcaa 780

atctccagtg cttcaacggg ggccagcaac gacaaccact acttcggcta cagcaccccc 840

tgggggtatt ttgacttcaa cagattccac tgccactttt caccacgtga ctggcaaaga 900

ctcatcaaca acaactgggg attccgaccc aagagactca acttcaagct ctttaacatt 960

caagtcaaag aggttacgga caacaatgga gtcaagacca tcgccaataa ccttaccagc 1020

acggtccagg tcttcacgga ctcagactat cagctcccgt acgtcctcgg ctctgcgcac 1080

cagggctgcc tccctccgtt cccggcggac gtgttcatga ttccgcagta cggctaccta 1140

acgctcaacg acggcagcca ggcagtggga cggtcatcct tttactgcct ggaatatttc 1200

ccatcgcaga tgctgagaac gggcaacaac tttaccttca gctacacctt tgaggacgtt 1260

cctttccaca gcagctacgc tcacagccag agtctggacc gtctcatgaa tcctctgatt 1320

gaccagtacc tgtactactt gtctaagact atcaacggat ccggccagaa tcagcagact 1380

ctgaagttca gccaaggtgg gcctaataca atggccaatc aggcaaagaa ctggctgcca 1440

ggaccctgtt accgccaaca acgcgtctca acgacaaccg ggcaaaacaa caatagcaac 1500

tttgcctgga ctgctgggac caaataccat ctgaatggaa gaaattcatt gatgaatcct 1560

ggccccgcta tggcatccca caaagagggc gaggaccgtt tttttcccct gtccgggtcc 1620

ctgatttttg gcaaacaaaa tgctgccaga gacaatgcgg attacagcga tgtcatgctc 1680

accagcgagg aagaaatcaa aaccactaac cctgtggcta cagaggaata cggtatcgtg 1740

gcagataact tgcagcagca aaacacggct cctcaaattg gaactgtcaa cagccagggg 1800

gccttacccg gtatggtctg gcagaaccgg gacgtgtacc tgcagggtcc catctgggcc 1860

aagattcctc acacggacgg caacttccac ccgtctccgc tgatgggcgg ctttggcctg 1920

aaacatcctc cgcctcagat cctgatcaag aacacgcctg tacctgcgga tcctccgacc 1980

accttcaacc agtcaaagct gaactctttc atcacgcaat acagcaccgg acaggtcagc 2040

gtggaaattg aatgggagct gcagaaggaa aacagcaagc gctggaaccc cgagatccag 2100

tacacctcca actactacaa atctacaagt gtggactttg ctgttaatac agaaggcgtg 2160

tactctgaac cccaccccat tggcacccgt tacctcaccc gtcccctgta a 2211

<210> 21

<211> 2211

<212> DNA

<213> 人工序列

<220>

<223> AAV214e8 VP1

<400> 21

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg cgctgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctgc aggcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gaccggtaga gccatcaccc cagcgttctc cagactcctc tacgggcatc 480

ggcaagaaag gccaacagcc cgccagaaaa agactcaatt ttggtcagac tggcgactca 540

gagtcagttc cagaccctca acctctcgga gaacctccag cagcgccctc tggtgtggga 600

cctaatacaa tggcttcagg cggtggcgca ccaatggcgg acaataacga aggcgccgac 660

ggagtgggta atgcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720

atcaccacca gcacccgcac ctgggccttg cccacctaca ataaccacct ctacaagcaa 780

atctccagtg cttcaacggg ggccagcaac gacaaccact acttcggcta cagcaccccc 840

tgggggtatt ttgacttcaa cagattccac tgccactttt caccacgtga ctggcaaaga 900

ctcatcaaca acaactgggg attccgaccc aagagactca acttcaagct ctttaacatt 960

caagtcaaag aggttacgga caacaatgga gtcaagacca tcgccaataa ccttaccagc 1020

acggtccagg tcttcacgga ctcagactat cagctcccgt acgtcctcgg ctctgcgcac 1080

cagggctgcc tccctccgtt cccggcggac gtgttcatga ttccgcagta cggctaccta 1140

acgctcaacg acggcagcca ggcagtggga cggtcatcct tttactgcct ggaatatttc 1200

ccatcgcaga tgctgagaac gggcaacaac tttaccttca gctacacctt tgaggacgtt 1260

cctttccaca gcagctacgc tcacagccag agtctggacc gtctcatgaa tcctctgatt 1320

gaccagtacc tgtactactt gtctaagact atcaacggat ccggccagaa tcagcagact 1380

ctgaagttca gccaaggtgg gcctaataca atggccaatc aggcaaagaa ctggctgcca 1440

ggaccctgtt accgccaaca acgcgtctca acgacaaccg ggcaaaacaa caatagcaac 1500

tttgcctgga ctgctgggac caaataccat ctgaatggaa gaaattcatt gatgaatcct 1560

ggccccgcta tggcatccca caaagagggc gaggaccgtt tttttcccct gtccgggtcc 1620

ctgatttttg gcaaacaaaa tgctgccaga gacaatgcgg attacagcga tgtcatgctc 1680

accagcgagg aagaaatcaa aaccactaac cctgtggcta cagaggaata cggtatcgtg 1740

gcagataact tgcagcagca aaacacggct cctcaaattg gaactgtcaa cagccagggg 1800

gccttacccg gtatggtctg gcagaaccgg gacgtgtacc tgcagggtcc catctgggcc 1860

aagattcctc acacggacgg caacttccac ccgtctccgc tgatgggcgg ctttggcctg 1920

aaacatcctc cgcctcagat cctgatcaag aacacgcctg tacctgcgga tcctccgacc 1980

accttcaacc agtcaaagct gaactctttc atcacgcaat acagcaccgg acaggtcagc 2040

gtggaaattg aatgggagct gcagaaggaa aacagcaagc gctggaaccc cgagatccag 2100

tacacctcca actactacaa atctacaagt gtggactttg ctgttaatac agaaggcgtg 2160

tactctgaac cccaccccat tggcacccgt tacctcaccc gtcccctgta a 2211

<210> 22

<211> 2208

<212> DNA

<213> 人工序列

<220>

<223> AAV214e9 VP1

<400> 22

atggctgccg atggttatct tccagattgg ctcgaggaca accttagtga aggaattcgc 60

gagtggtggg ctttgaaacc tggagcccct caacccaagg caaatcaaca acatcaagac 120

aacgctcgag gtcttgtgct tccgggttac aaataccttg gacccggcaa cggactcgac 180

aagggggagc cggtcaacgc agcagacgcg gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aggccggaga caacccgtac ctcaagtaca accacgccga cgccgagttc 300

caggagcggc tcaaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaaaaaga ggcttcttga acctcttggt ctggttgagg aagcggctaa gacggctcct 420

ggaaagaaga ggcctgtaga gcagtctccc caggaaccgg actcctccgc gggtattggc 480

aaatcgggtg cacagcccgc taaaaagaga ctcaatttcg gtcagactgg cgacacagag 540

tcagtcccag accctcaacc aatcggagaa cctcccgcag ccccctctgg tgtgggatct 600

cttacaatgg cttcaggcgg tggcgcacca atggcggaca ataacgaagg cgccgacgga 660

gtgggtaatg cctcaggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc 720

accaccagca cccgcacctg ggccttgccc acctacaata accacctcta caagcaaatc 780

tccagtgctt caacgggggc cagcaacgac aaccactact tcggctacag caccccctgg 840

gggtattttg acttcaacag attccactgc cacttttcac cacgtgactg gcaaagactc 900

atcaacaaca actggggatt ccgacccaag agactcaact tcaagctctt taacattcaa 960

gtcaaagagg ttacggacaa caatggagtc aagaccatcg ccaataacct taccagcacg 1020

gtccaggtct tcacggactc agactatcag ctcccgtacg tcctcggctc tgcgcaccag 1080

ggctgcctcc ctccgttccc ggcggacgtg ttcatgattc cgcagtacgg ctacctaacg 1140

ctcaacgacg gcagccaggc agtgggacgg tcatcctttt actgcctgga atatttccca 1200

tcgcagatgc tgagaacggg caacaacttt accttcagct acacctttga ggacgttcct 1260

ttccacagca gctacgctca cagccagagt ctggaccgtc tcatgaatcc tctgattgac 1320

cagtacctgt actacttgtc taagactatc aacggatccg gccagaatca gcagactctg 1380

aagttcagcc aaggtgggcc taatacaatg gccaatcagg caaagaactg gctgccagga 1440

ccctgttacc gccaacaacg cgtctcaacg acaaccgggc aaaacaacaa tagcaacttt 1500

gcctggactg ctgggaccaa ataccatctg aatggaagaa attcattgat gaatcctggc 1560

cccgctatgg catcccacaa agagggcgag gaccgttttt ttcccctgtc cgggtccctg 1620

atttttggca aacaaaatgc tgccagagac aatgcggatt acagcgatgt catgctcacc 1680

agcgaggaag aaatcaaaac cactaaccct gtggctacag aggaatacgg tatcgtggca 1740

gataacttgc agcagcaaaa cacggctcct caaattggaa ctgtcaacag ccagggggcc 1800

ttacccggta tggtctggca gaaccgggac gtgtacctgc agggtcccat ctgggccaag 1860

attcctcaca cggacggcaa cttccacccg tctccgctga tgggcggctt tggcctgaaa 1920

catcctccgc ctcagatcct gatcaagaac acgcctgtac ctgcggatcc tccgaccacc 1980

ttcaaccagt caaagctgaa ctctttcatc acgcaataca gcaccggaca ggtcagcgtg 2040

gaaattgaat gggagctgca gaaggaaaac agcaagcgct ggaaccccga gatccagtac 2100

acctccaact actacaaatc tacaagtgtg gactttgctg ttaatacaga aggcgtgtac 2160

tctgaacccc accccattgg cacccgttac ctcacccgtc ccctgtaa 2208

<210> 23

<211> 2211

<212> DNA

<213> 人工序列

<220>

<223> AAV214e10 VP1

<400> 23

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gaccggtaga gccatcaccc cagcgttctc cagactcctc tacgggcatc 480

ggcaagaaag gccagcagcc cgcgaaaaag agactcaact ttgggcagac tggcgactca 540

gagtcagtgc ccgaccctca accaatcgga gaaccccccg caggcccctc tggtctggga 600

tctggtacaa tggcttcagg cggtggcgca ccaatggcgg acaataacga aggcgccgac 660

ggagtgggta atgcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720

atcaccacca gcacccgcac ctgggccttg cccacctaca ataaccacct ctacaagcaa 780

atctccagtg cttcaacggg ggccagcaac gacaaccact acttcggcta cagcaccccc 840

tgggggtatt ttgacttcaa cagattccac tgccactttt caccacgtga ctggcaaaga 900

ctcatcaaca acaactgggg attccgaccc aagagactca acttcaagct ctttaacatt 960

caagtcaaag aggttacgga caacaatgga gtcaagacca tcgccaataa ccttaccagc 1020

acggtccagg tcttcacgga ctcagactat cagctcccgt acgtcctcgg ctctgcgcac 1080

cagggctgcc tccctccgtt cccggcggac gtgttcatga ttccgcagta cggctaccta 1140

acgctcaacg acggcagcca ggcagtggga cggtcatcct tttactgcct ggaatatttc 1200

ccatcgcaga tgctgagaac gggcaacaac tttaccttca gctacacctt tgaggacgtt 1260

cctttccaca gcagctacgc tcacagccag agtctggacc gtctcatgaa tcctctgatt 1320

gaccagtacc tgtactactt gtctaagact atcaacggat ccggccagaa tcagcagact 1380

ctgaagttca gccaaggtgg gcctaataca atggccaatc aggcaaagaa ctggctgcca 1440

ggaccctgtt accgccaaca acgcgtctca acgacaaccg ggcaaaacaa caatagcaac 1500

tttgcctgga ctgctgggac caaataccat ctgaatggaa gaaattcatt gatgaatcct 1560

ggccccgcta tggcatccca caaagagggc gaggaccgtt tttttcccct gtccgggtcc 1620

ctgatttttg gcaaacaaaa tgctgccaga gacaatgcgg attacagcga tgtcatgctc 1680

accagcgagg aagaaatcaa aaccactaac cctgtggcta cagaggaata cggtatcgtg 1740

gcagataact tgcagcagca aaacacggct cctcaaattg gaactgtcaa cagccagggg 1800

gccttacccg gtatggtctg gcagaaccgg gacgtgtacc tgcagggtcc catctgggcc 1860

aagattcctc acacggacgg caacttccac ccgtctccgc tgatgggcgg ctttggcctg 1920

aaacatcctc cgcctcagat cctgatcaag aacacgcctg tacctgcgga tcctccgacc 1980

accttcaacc agtcaaagct gaactctttc atcacgcaat acagcaccgg acaggtcagc 2040

gtggaaattg aatgggagct gcagaaggaa aacagcaagc gctggaaccc cgagatccag 2100

tacacctcca actactacaa atctacaagt gtggactttg ctgttaatac agaaggcgtg 2160

tactctgaac cccaccccat tggcacccgt tacctcaccc gtcccctgta a 2211

<210> 24

<211> 1602

<212> DNA

<213> 人工序列

<220>

<223> ITB102 214 (AAV214) VP3

<400> 24

atggcttcag gcggtggcgc accaatggcg gacaataacg aaggcgccga cggagtgggt 60

aatgcctcag gaaattggca ttgcgattcc acatggctgg gcgacagagt catcaccacc 120

agcacccgca cctgggcctt gcccacctac aataaccacc tctacaagca aatctccagt 180

gcttcaacgg gggccagcaa cgacaaccac tacttcggct acagcacccc ctgggggtat 240

tttgacttca acagattcca ctgccacttt tcaccacgtg actggcaaag actcatcaac 300

aacaactggg gattccgacc caagagactc aacttcaagc tctttaacat tcaagtcaaa 360

gaggttacgg acaacaatgg agtcaagacc atcgccaata accttaccag cacggtccag 420

gtcttcacgg actcagacta tcagctcccg tacgtcctcg gctctgcgca ccagggctgc 480

ctccctccgt tcccggcgga cgtgttcatg attccgcagt acggctacct aacgctcaac 540

gacggcagcc aggcagtggg acggtcatcc ttttactgcc tggaatattt cccatcgcag 600

atgctgagaa cgggcaacaa ctttaccttc agctacacct ttgaggacgt tcctttccac 660

agcagctacg ctcacagcca gagtctggac cgtctcatga atcctctgat tgaccagtac 720

ctgtactact tgtctaagac tatcaacgga tccggccaga atcagcagac tctgaagttc 780

agccaaggtg ggcctaatac aatggccaat caggcaaaga actggctgcc aggaccctgt 840

taccgccaac aacgcgtctc aacgacaacc gggcaaaaca acaatagcaa ctttgcctgg 900

actgctggga ccaaatacca tctgaatgga agaaattcat tgatgaatcc tggccccgct 960

atggcatccc acaaagaggg cgaggaccgt ttttttcccc tgtccgggtc cctgattttt 1020

ggcaaacaaa atgctgccag agacaatgcg gattacagcg atgtcatgct caccagcgag 1080

gaagaaatca aaaccactaa ccctgtggct acagaggaat acggtatcgt ggcagataac 1140

ttgcagcagc aaaacacggc tcctcaaatt ggaactgtca acagccaggg ggccttaccc 1200

ggtatggtct ggcagaaccg ggacgtgtac ctgcagggtc ccatctgggc caagattcct 1260

cacacggacg gcaacttcca cccgtctccg ctgatgggcg gctttggcct gaaacatcct 1320

ccgcctcaga tcctgatcaa gaacacgcct gtacctgcgg atcctccgac caccttcaac 1380

cagtcaaagc tgaactcttt catcacgcaa tacagcaccg gacaggtcag cgtggaaatt 1440

gaatgggagc tgcagaagga aaacagcaag cgctggaacc ccgagatcca gtacacctcc 1500

aactactaca aatctacaag tgtggacttt gctgttaata cagaaggcgt gtactctgaa 1560

ccccacccca ttggcacccg ttacctcacc cgtcccctgt aa 1602

<210> 25

<211> 1605

<212> DNA

<213> 人工序列

<220>

<223> AAV214-A VP3

<400> 25

atggcttcag gcggtggcgc accaatggcg gacaataacg aaggcgccga cggagtgggt 60

aatgcctcag gaaattggca ttgcgattcc acatggctgg gcgacagagt catcaccacc 120

agcacccgca cctgggcctt gcccacctac aataaccacc tctacaagca aatctccaac 180

agcacatctg gaggatcttc aaatgacaac gcctacttcg gctacagcac cccctggggg 240

tattttgact tcaacagatt ccactgccac ttttcaccac gtgactggca aagactcatc 300

aacaacaact ggggattccg acccaagaga ctcaacttca agctctttaa cattcaagtc 360

aaagaggtta cggacaacaa tggagtcaag accatcgcca ataaccttac cagcacggtc 420

caggtcttca cggactcaga ctatcagctc ccgtacgtcc tcggctctgc gcaccagggc 480

tgcctccctc cgttcccggc ggacgtgttc atgattccgc agtacggcta cctaacgctc 540

aacgacggca gccaggcagt gggacggtca tccttttact gcctggaata tttcccatcg 600

cagatgctga gaacgggcaa caactttacc ttcagctaca cctttgagga cgttcctttc 660

cacagcagct acgctcacag ccagagtctg gaccgtctca tgaatcctct gattgaccag 720

tacctgtact acttgtctaa gactatcaac ggatccggcc agaatcagca gactctgaag 780

ttcagccaag gtgggcctaa tacaatggcc aatcaggcaa agaactggct gccaggaccc 840

tgttaccgcc aacaacgcgt ctcaacgaca accgggcaaa acaacaatag caactttgcc 900

tggactgctg ggaccaaata ccatctgaat ggaagaaatt cattgatgaa tcctggcccc 960

gctatggcat cccacaaaga gggcgaggac cgtttttttc ccctgtccgg gtccctgatt 1020

tttggcaaac aaaatgctgc cagagacaat gcggattaca gcgatgtcat gctcaccagc 1080

gaggaagaaa tcaaaaccac taaccctgtg gctacagagg aatacggtat cgtggcagat 1140

aacttgcagc agcaaaacac ggctcctcaa attggaactg tcaacagcca gggggcctta 1200

cccggtatgg tctggcagaa ccgggacgtg tacctgcagg gtcccatctg ggccaagatt 1260

cctcacacgg acggcaactt ccacccgtct ccgctgatgg gcggctttgg cctgaaacat 1320

cctccgcctc agatcctgat caagaacacg cctgtacctg cggatcctcc gaccaccttc 1380

aaccagtcaa agctgaactc tttcatcacg caatacagca ccggacaggt cagcgtggaa 1440

attgaatggg agctgcagaa ggaaaacagc aagcgctgga accccgagat ccagtacacc 1500

tccaactact acaaatctac aagtgtggac tttgctgtta atacagaagg cgtgtactct 1560

gaaccccacc ccattggcac ccgttacctc acccgtcccc tgtaa 1605

<210> 26

<211> 1602

<212> DNA

<213> 人工序列

<220>

<223> AAV214e VP3

<400> 26

atggcttcag gcggtggcgc accaatggca gacaataacg aaggcgccga cggagtgggt 60

aatgcctcag gaaattggca ttgcgattcc acatggctgg gcgacagagt catcaccacc 120

agcacccgca cctgggcctt gcccacctac aataaccacc tctacaagca aatctccagt 180

gcttcaacgg gggccagcaa cgacaaccac tacttcggct acagcacccc ctgggggtat 240

tttgacttca acagattcca ctgccacttt tcaccacgtg actggcaaag actcatcaac 300

aacaactggg gattccgacc caagagactc aacttcaagc tctttaacat tcaagtcaaa 360

gaggttacgg acaacaatgg agtcaagacc atcgccaata accttaccag cacggtccag 420

gtcttcacgg actcagacta tcagctcccg tacgtcctcg gctctgcgca ccagggctgc 480

ctccctccgt tcccggcgga cgtgttcatg attccgcagt acggctacct aacgctcaac 540

gacggcagcc aggcagtggg acggtcatcc ttttactgcc tggaatattt cccatcgcag 600

atgctgagaa cgggcaacaa ctttaccttc agctacacct ttgaggacgt tcctttccac 660

agcagctacg ctcacagcca gagtctggac cgtctcatga atcctctgat tgaccagtac 720

ctgtactact tgtctaagac tatcaacgga tccggccaga atcagcagac tctgaagttc 780

agccaaggtg ggcctaatac aatggccaat caggcaaaga actggctgcc aggaccctgt 840

taccgccaac aacgcgtctc aacgacaacc gggcaaaaca acaatagcaa ctttgcctgg 900

actgctggga ccaaatacca tctgaatgga agaaattcat tgatgaatcc tggccccgct 960

atggcatccc acaaagaggg cgaggaccgt ttttttcccc tgtccgggtc cctgattttt 1020

ggcaaacaaa atgctgccag agacaatgcg gattacagcg atgtcatgct caccagcgag 1080

gaagaaatca aaaccactaa ccctgtggct acagaggaat acggtatcgt ggcagataac 1140

ttgcagcagc aaaacacggc tcctcaaatt ggaactgtca acagccaggg ggccttaccc 1200

ggtatggtct ggcagaaccg ggacgtgtac ctgcagggtc ccatctgggc caagattcct 1260

cacacggacg gcaacttcca cccgtctccg ctgatgggcg gctttggcct gaaacatcct 1320

ccgcctcaga tcctgatcaa gaacacgcct gtacctgcgg atcctccgac caccttcaac 1380

cagtcaaagc tgaactcttt catcacgcaa tacagcaccg gacaggtcag cgtggaaatt 1440

gaatgggagc tgcagaagga aaacagcaag cgctggaacc ccgagatcca gtacacctcc 1500

aactactaca aatctacaag tgtggacttt gctgttaata cagaaggcgt gtactctgaa 1560

ccccacccca ttggcacccg ttacctcacc cgtcccctgt aa 1602

<210> 27

<211> 1602

<212> DNA

<213> 人工序列

<220>

<223> AAV214e8 VP3

<400> 27

atggcttcag gcggtggcgc accaatggcg gacaataacg aaggcgccga cggagtgggt 60

aatgcctcag gaaattggca ttgcgattcc acatggctgg gcgacagagt catcaccacc 120

agcacccgca cctgggcctt gcccacctac aataaccacc tctacaagca aatctccagt 180

gcttcaacgg gggccagcaa cgacaaccac tacttcggct acagcacccc ctgggggtat 240

tttgacttca acagattcca ctgccacttt tcaccacgtg actggcaaag actcatcaac 300

aacaactggg gattccgacc caagagactc aacttcaagc tctttaacat tcaagtcaaa 360

gaggttacgg acaacaatgg agtcaagacc atcgccaata accttaccag cacggtccag 420

gtcttcacgg actcagacta tcagctcccg tacgtcctcg gctctgcgca ccagggctgc 480

ctccctccgt tcccggcgga cgtgttcatg attccgcagt acggctacct aacgctcaac 540

gacggcagcc aggcagtggg acggtcatcc ttttactgcc tggaatattt cccatcgcag 600

atgctgagaa cgggcaacaa ctttaccttc agctacacct ttgaggacgt tcctttccac 660

agcagctacg ctcacagcca gagtctggac cgtctcatga atcctctgat tgaccagtac 720

ctgtactact tgtctaagac tatcaacgga tccggccaga atcagcagac tctgaagttc 780

agccaaggtg ggcctaatac aatggccaat caggcaaaga actggctgcc aggaccctgt 840

taccgccaac aacgcgtctc aacgacaacc gggcaaaaca acaatagcaa ctttgcctgg 900

actgctggga ccaaatacca tctgaatgga agaaattcat tgatgaatcc tggccccgct 960

atggcatccc acaaagaggg cgaggaccgt ttttttcccc tgtccgggtc cctgattttt 1020

ggcaaacaaa atgctgccag agacaatgcg gattacagcg atgtcatgct caccagcgag 1080

gaagaaatca aaaccactaa ccctgtggct acagaggaat acggtatcgt ggcagataac 1140

ttgcagcagc aaaacacggc tcctcaaatt ggaactgtca acagccaggg ggccttaccc 1200

ggtatggtct ggcagaaccg ggacgtgtac ctgcagggtc ccatctgggc caagattcct 1260

cacacggacg gcaacttcca cccgtctccg ctgatgggcg gctttggcct gaaacatcct 1320

ccgcctcaga tcctgatcaa gaacacgcct gtacctgcgg atcctccgac caccttcaac 1380

cagtcaaagc tgaactcttt catcacgcaa tacagcaccg gacaggtcag cgtggaaatt 1440

gaatgggagc tgcagaagga aaacagcaag cgctggaacc ccgagatcca gtacacctcc 1500

aactactaca aatctacaag tgtggacttt gctgttaata cagaaggcgt gtactctgaa 1560

ccccacccca ttggcacccg ttacctcacc cgtcccctgt aa 1602

<210> 28

<211> 1602

<212> DNA

<213> 人工序列

<220>

<223> AAV214e9 VP3

<400> 28

atggcttcag gcggtggcgc accaatggcg gacaataacg aaggcgccga cggagtgggt 60

aatgcctcag gaaattggca ttgcgattcc acatggctgg gcgacagagt catcaccacc 120

agcacccgca cctgggcctt gcccacctac aataaccacc tctacaagca aatctccagt 180

gcttcaacgg gggccagcaa cgacaaccac tacttcggct acagcacccc ctgggggtat 240

tttgacttca acagattcca ctgccacttt tcaccacgtg actggcaaag actcatcaac 300

aacaactggg gattccgacc caagagactc aacttcaagc tctttaacat tcaagtcaaa 360

gaggttacgg acaacaatgg agtcaagacc atcgccaata accttaccag cacggtccag 420

gtcttcacgg actcagacta tcagctcccg tacgtcctcg gctctgcgca ccagggctgc 480

ctccctccgt tcccggcgga cgtgttcatg attccgcagt acggctacct aacgctcaac 540

gacggcagcc aggcagtggg acggtcatcc ttttactgcc tggaatattt cccatcgcag 600

atgctgagaa cgggcaacaa ctttaccttc agctacacct ttgaggacgt tcctttccac 660

agcagctacg ctcacagcca gagtctggac cgtctcatga atcctctgat tgaccagtac 720

ctgtactact tgtctaagac tatcaacgga tccggccaga atcagcagac tctgaagttc 780

agccaaggtg ggcctaatac aatggccaat caggcaaaga actggctgcc aggaccctgt 840

taccgccaac aacgcgtctc aacgacaacc gggcaaaaca acaatagcaa ctttgcctgg 900

actgctggga ccaaatacca tctgaatgga agaaattcat tgatgaatcc tggccccgct 960

atggcatccc acaaagaggg cgaggaccgt ttttttcccc tgtccgggtc cctgattttt 1020

ggcaaacaaa atgctgccag agacaatgcg gattacagcg atgtcatgct caccagcgag 1080

gaagaaatca aaaccactaa ccctgtggct acagaggaat acggtatcgt ggcagataac 1140

ttgcagcagc aaaacacggc tcctcaaatt ggaactgtca acagccaggg ggccttaccc 1200

ggtatggtct ggcagaaccg ggacgtgtac ctgcagggtc ccatctgggc caagattcct 1260

cacacggacg gcaacttcca cccgtctccg ctgatgggcg gctttggcct gaaacatcct 1320

ccgcctcaga tcctgatcaa gaacacgcct gtacctgcgg atcctccgac caccttcaac 1380

cagtcaaagc tgaactcttt catcacgcaa tacagcaccg gacaggtcag cgtggaaatt 1440

gaatgggagc tgcagaagga aaacagcaag cgctggaacc ccgagatcca gtacacctcc 1500

aactactaca aatctacaag tgtggacttt gctgttaata cagaaggcgt gtactctgaa 1560

ccccacccca ttggcacccg ttacctcacc cgtcccctgt aa 1602

<210> 29

<211> 1602

<212> DNA

<213> 人工序列

<220>

<223> AAV214e10 VP3

<400> 29

atggcttcag gcggtggcgc accaatggcg gacaataacg aaggcgccga cggagtgggt 60

aatgcctcag gaaattggca ttgcgattcc acatggctgg gcgacagagt catcaccacc 120

agcacccgca cctgggcctt gcccacctac aataaccacc tctacaagca aatctccagt 180

gcttcaacgg gggccagcaa cgacaaccac tacttcggct acagcacccc ctgggggtat 240

tttgacttca acagattcca ctgccacttt tcaccacgtg actggcaaag actcatcaac 300

aacaactggg gattccgacc caagagactc aacttcaagc tctttaacat tcaagtcaaa 360

gaggttacgg acaacaatgg agtcaagacc atcgccaata accttaccag cacggtccag 420

gtcttcacgg actcagacta tcagctcccg tacgtcctcg gctctgcgca ccagggctgc 480

ctccctccgt tcccggcgga cgtgttcatg attccgcagt acggctacct aacgctcaac 540

gacggcagcc aggcagtggg acggtcatcc ttttactgcc tggaatattt cccatcgcag 600

atgctgagaa cgggcaacaa ctttaccttc agctacacct ttgaggacgt tcctttccac 660

agcagctacg ctcacagcca gagtctggac cgtctcatga atcctctgat tgaccagtac 720

ctgtactact tgtctaagac tatcaacgga tccggccaga atcagcagac tctgaagttc 780

agccaaggtg ggcctaatac aatggccaat caggcaaaga actggctgcc aggaccctgt 840

taccgccaac aacgcgtctc aacgacaacc gggcaaaaca acaatagcaa ctttgcctgg 900

actgctggga ccaaatacca tctgaatgga agaaattcat tgatgaatcc tggccccgct 960

atggcatccc acaaagaggg cgaggaccgt ttttttcccc tgtccgggtc cctgattttt 1020

ggcaaacaaa atgctgccag agacaatgcg gattacagcg atgtcatgct caccagcgag 1080

gaagaaatca aaaccactaa ccctgtggct acagaggaat acggtatcgt ggcagataac 1140

ttgcagcagc aaaacacggc tcctcaaatt ggaactgtca acagccaggg ggccttaccc 1200

ggtatggtct ggcagaaccg ggacgtgtac ctgcagggtc ccatctgggc caagattcct 1260

cacacggacg gcaacttcca cccgtctccg ctgatgggcg gctttggcct gaaacatcct 1320

ccgcctcaga tcctgatcaa gaacacgcct gtacctgcgg atcctccgac caccttcaac 1380

cagtcaaagc tgaactcttt catcacgcaa tacagcaccg gacaggtcag cgtggaaatt 1440

gaatgggagc tgcagaagga aaacagcaag cgctggaacc ccgagatcca gtacacctcc 1500

aactactaca aatctacaag tgtggacttt gctgttaata cagaaggcgt gtactctgaa 1560

ccccacccca ttggcacccg ttacctcacc cgtcccctgt aa 1602

<210> 30

<211> 736

<212> PRT

<213> 人工序列

<220>

<223> AAV214A VP1

<400> 30

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Phe Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn

260 265 270

Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp

370 375 380

Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser

435 440 445

Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser

450 455 460

Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln Asn

485 490 495

Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu Asn

500 505 510

Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys

515 520 525

Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly

530 535 540

Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val Met Leu

545 550 555 560

Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Glu

565 570 575

Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln

580 585 590

Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn

690 695 700

Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly Val

705 710 715 720

Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 31

<211> 736

<212> PRT

<213> 人工序列

<220>

<223> AAV214e VP1

<400> 31

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro

180 185 190

Pro Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn

210 215 220

Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn

260 265 270

His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp

370 375 380

Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser

435 440 445

Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser

450 455 460

Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln Asn

485 490 495

Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu Asn

500 505 510

Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys

515 520 525

Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly

530 535 540

Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val Met Leu

545 550 555 560

Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Glu

565 570 575

Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln

580 585 590

Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn

690 695 700

Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly Val

705 710 715 720

Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 32

<211> 736

<212> PRT

<213> 人工序列

<220>

<223> AAV214e8 VP1

<400> 32

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Gln Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro

180 185 190

Pro Ala Ala Pro Ser Gly Val Gly Pro Asn Thr Met Ala Ser Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn

210 215 220

Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn

260 265 270

His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp

370 375 380

Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser

435 440 445

Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser

450 455 460

Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln Asn

485 490 495

Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu Asn

500 505 510

Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys

515 520 525

Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly

530 535 540

Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val Met Leu

545 550 555 560

Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Glu

565 570 575

Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln

580 585 590

Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn

690 695 700

Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly Val

705 710 715 720

Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 33

<211> 735

<212> PRT

<213> 人工序列

<220>

<223> AAV214e9 VP1

<400> 33

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Gln Pro

20 25 30

Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ala Gly Ile Gly

145 150 155 160

Lys Ser Gly Ala Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro

180 185 190

Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His

260 265 270

Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe

275 280 285

His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn

290 295 300

Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln

305 310 315 320

Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn Asn

325 330 335

Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu Pro

340 345 350

Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala

355 360 365

Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp Gly

370 375 380

Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro

385 390 395 400

Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe

405 410 415

Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp

420 425 430

Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Lys

435 440 445

Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser Gln

450 455 460

Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu Pro Gly

465 470 475 480

Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln Asn Asn

485 490 495

Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu Asn Gly

500 505 510

Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys Glu

515 520 525

Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly Lys

530 535 540

Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val Met Leu Thr

545 550 555 560

Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Glu Tyr

565 570 575

Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln Ile

580 585 590

Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln Asn

595 600 605

Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr

610 615 620

Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys

625 630 635 640

His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp

645 650 655

Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr Gln

660 665 670

Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys

675 680 685

Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr

690 695 700

Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly Val Tyr

705 710 715 720

Ser Glu Pro His Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 34

<211> 736

<212> PRT

<213> 人工序列

<220>

<223> AAV214e10 VP1

<400> 34

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro

180 185 190

Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ser Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn

210 215 220

Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn

260 265 270

His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp

370 375 380

Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser

435 440 445

Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser

450 455 460

Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln Asn

485 490 495

Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu Asn

500 505 510

Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys

515 520 525

Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly

530 535 540

Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val Met Leu

545 550 555 560

Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Glu

565 570 575

Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln

580 585 590

Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn

690 695 700

Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly Val

705 710 715 720

Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 35

<211> 598

<212> PRT

<213> 人工序列

<220>

<223> AAV214 VP2

<400> 35

Met Ala Pro Gly Lys Lys Arg Pro Val Glu Gln Ser Pro Gln Glu Pro

1 5 10 15

Asp Ser Ser Ser Gly Ile Gly Lys Thr Gly Gln Gln Pro Ala Lys Lys

20 25 30

Arg Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu Ser Val Pro Asp Pro

35 40 45

Gln Pro Leu Gly Glu Pro Pro Ala Thr Pro Ala Ala Val Gly Pro Thr

50 55 60

Thr Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly

65 70 75 80

Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr

85 90 95

Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu

100 105 110

Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr

115 120 125

Gly Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly

130 135 140

Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp

145 150 155 160

Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn

165 170 175

Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly

180 185 190

Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr

195 200 205

Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly

210 215 220

Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly

225 230 235 240

Tyr Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser Phe

245 250 255

Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn

260 265 270

Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr

275 280 285

Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln

290 295 300

Tyr Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln

305 310 315 320

Gln Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln

325 330 335

Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser

340 345 350

Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly

355 360 365

Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly Pro

370 375 380

Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser

385 390 395 400

Gly Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp

405 410 415

Tyr Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn

420 425 430

Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln

435 440 445

Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu

450 455 460

Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile

465 470 475 480

Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu

485 490 495

Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys

500 505 510

Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys

515 520 525

Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu

530 535 540

Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu

545 550 555 560

Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala

565 570 575

Val Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr Arg

580 585 590

Tyr Leu Thr Arg Pro Leu

595

<210> 36

<211> 599

<212> PRT

<213> 人工序列

<220>

<223> AAV214A VP2

<400> 36

Met Ala Pro Gly Lys Lys Arg Pro Val Glu Gln Ser Pro Gln Glu Pro

1 5 10 15

Asp Ser Ser Ser Gly Ile Gly Lys Thr Gly Gln Gln Pro Ala Lys Lys

20 25 30

Arg Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu Ser Val Pro Asp Pro

35 40 45

Gln Pro Leu Gly Glu Pro Pro Ala Thr Pro Ala Ala Val Gly Pro Thr

50 55 60

Thr Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly

65 70 75 80

Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr

85 90 95

Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu

100 105 110

Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Asn Ser Thr Ser

115 120 125

Gly Gly Ser Ser Asn Asp Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp

130 135 140

Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp

145 150 155 160

Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu

165 170 175

Asn Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn

180 185 190

Gly Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe

195 200 205

Thr Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln

210 215 220

Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr

225 230 235 240

Gly Tyr Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser

245 250 255

Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn

260 265 270

Asn Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser

275 280 285

Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp

290 295 300

Gln Tyr Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn

305 310 315 320

Gln Gln Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn

325 330 335

Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val

340 345 350

Ser Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala

355 360 365

Gly Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly

370 375 380

Pro Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu

385 390 395 400

Ser Gly Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala

405 410 415

Asp Tyr Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr

420 425 430

Asn Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln

435 440 445

Gln Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala

450 455 460

Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro

465 470 475 480

Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro

485 490 495

Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile

500 505 510

Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser

515 520 525

Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val

530 535 540

Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro

545 550 555 560

Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe

565 570 575

Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr

580 585 590

Arg Tyr Leu Thr Arg Pro Leu

595

<210> 37

<211> 599

<212> PRT

<213> 人工序列

<220>

<223> AAV214e VP2

<400> 37

Met Ala Pro Gly Lys Lys Arg Pro Val Glu Pro Ser Pro Gln Arg Ser

1 5 10 15

Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gln Gln Pro Ala Arg

20 25 30

Lys Arg Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu Ser Val Pro Asp

35 40 45

Pro Gln Pro Leu Gly Glu Pro Pro Ala Thr Pro Ala Ala Val Gly Pro

50 55 60

Thr Thr Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu

65 70 75 80

Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser

85 90 95

Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala

100 105 110

Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser

115 120 125

Thr Gly Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp

130 135 140

Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp

145 150 155 160

Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu

165 170 175

Asn Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn

180 185 190

Gly Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe

195 200 205

Thr Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln

210 215 220

Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr

225 230 235 240

Gly Tyr Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser

245 250 255

Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn

260 265 270

Asn Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser

275 280 285

Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp

290 295 300

Gln Tyr Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn

305 310 315 320

Gln Gln Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn

325 330 335

Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val

340 345 350

Ser Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala

355 360 365

Gly Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly

370 375 380

Pro Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu

385 390 395 400

Ser Gly Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala

405 410 415

Asp Tyr Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr

420 425 430

Asn Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln

435 440 445

Gln Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala

450 455 460

Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro

465 470 475 480

Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro

485 490 495

Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile

500 505 510

Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser

515 520 525

Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val

530 535 540

Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro

545 550 555 560

Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe

565 570 575

Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr

580 585 590

Arg Tyr Leu Thr Arg Pro Leu

595

<210> 38

<211> 599

<212> PRT

<213> 人工序列

<220>

<223> AAV214e8 VP2

<400> 38

Met Ala Pro Gly Lys Lys Arg Pro Val Glu Pro Ser Pro Gln Arg Ser

1 5 10 15

Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gln Gln Pro Ala Arg

20 25 30

Lys Arg Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu Ser Val Pro Asp

35 40 45

Pro Gln Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser Gly Val Gly Pro

50 55 60

Asn Thr Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu

65 70 75 80

Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser

85 90 95

Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala

100 105 110

Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser

115 120 125

Thr Gly Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp

130 135 140

Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp

145 150 155 160

Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu

165 170 175

Asn Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn

180 185 190

Gly Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe

195 200 205

Thr Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln

210 215 220

Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr

225 230 235 240

Gly Tyr Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser

245 250 255

Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn

260 265 270

Asn Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser

275 280 285

Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp

290 295 300

Gln Tyr Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn

305 310 315 320

Gln Gln Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn

325 330 335

Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val

340 345 350

Ser Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala

355 360 365

Gly Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly

370 375 380

Pro Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu

385 390 395 400

Ser Gly Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala

405 410 415

Asp Tyr Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr

420 425 430

Asn Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln

435 440 445

Gln Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala

450 455 460

Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro

465 470 475 480

Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro

485 490 495

Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile

500 505 510

Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser

515 520 525

Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val

530 535 540

Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro

545 550 555 560

Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe

565 570 575

Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr

580 585 590

Arg Tyr Leu Thr Arg Pro Leu

595

<210> 39

<211> 598

<212> PRT

<213> 人工序列

<220>

<223> AAV214e9 VP2

<400> 39

Met Ala Pro Gly Lys Lys Arg Pro Val Glu Gln Ser Pro Gln Glu Pro

1 5 10 15

Asp Ser Ser Ala Gly Ile Gly Lys Ser Gly Ala Gln Pro Ala Lys Lys

20 25 30

Arg Leu Asn Phe Gly Gln Thr Gly Asp Thr Glu Ser Val Pro Asp Pro

35 40 45

Gln Pro Ile Gly Glu Pro Pro Ala Ala Pro Ser Gly Val Gly Ser Leu

50 55 60

Thr Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly

65 70 75 80

Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr

85 90 95

Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu

100 105 110

Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr

115 120 125

Gly Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly

130 135 140

Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp

145 150 155 160

Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn

165 170 175

Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly

180 185 190

Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr

195 200 205

Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly

210 215 220

Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly

225 230 235 240

Tyr Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser Phe

245 250 255

Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn

260 265 270

Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr

275 280 285

Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln

290 295 300

Tyr Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln

305 310 315 320

Gln Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln

325 330 335

Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser

340 345 350

Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly

355 360 365

Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly Pro

370 375 380

Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser

385 390 395 400

Gly Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp

405 410 415

Tyr Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn

420 425 430

Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln

435 440 445

Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu

450 455 460

Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile

465 470 475 480

Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu

485 490 495

Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys

500 505 510

Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys

515 520 525

Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu

530 535 540

Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu

545 550 555 560

Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala

565 570 575

Val Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr Arg

580 585 590

Tyr Leu Thr Arg Pro Leu

595

<210> 40

<211> 599

<212> PRT

<213> 人工序列

<220>

<223> AAV214e10 VP2

<400> 40

Met Ala Pro Gly Lys Lys Arg Pro Val Glu Pro Ser Pro Gln Arg Ser

1 5 10 15

Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gln Gln Pro Ala Lys

20 25 30

Lys Arg Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu Ser Val Pro Asp

35 40 45

Pro Gln Pro Ile Gly Glu Pro Pro Ala Gly Pro Ser Gly Leu Gly Ser

50 55 60

Gly Thr Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu

65 70 75 80

Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser

85 90 95

Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala

100 105 110

Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser

115 120 125

Thr Gly Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp

130 135 140

Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp

145 150 155 160

Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu

165 170 175

Asn Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn

180 185 190

Gly Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe

195 200 205

Thr Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln

210 215 220

Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr

225 230 235 240

Gly Tyr Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser

245 250 255

Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn

260 265 270

Asn Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser

275 280 285

Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp

290 295 300

Gln Tyr Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn

305 310 315 320

Gln Gln Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn

325 330 335

Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val

340 345 350

Ser Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala

355 360 365

Gly Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly

370 375 380

Pro Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu

385 390 395 400

Ser Gly Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala

405 410 415

Asp Tyr Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr

420 425 430

Asn Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln

435 440 445

Gln Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala

450 455 460

Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro

465 470 475 480

Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro

485 490 495

Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile

500 505 510

Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser

515 520 525

Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val

530 535 540

Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro

545 550 555 560

Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe

565 570 575

Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr

580 585 590

Arg Tyr Leu Thr Arg Pro Leu

595

<210> 41

<211> 533

<212> PRT

<213> 人工序列

<220>

<223> AAV214 VP3

<400> 41

Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly

50 55 60

Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr

65 70 75 80

Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln

85 90 95

Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe

100 105 110

Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val

115 120 125

Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp

130 135 140

Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys

145 150 155 160

Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr

165 170 175

Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr

180 185 190

Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe

195 200 205

Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala

210 215 220

His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr

225 230 235 240

Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln

245 250 255

Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala

260 265 270

Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr

275 280 285

Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr

290 295 300

Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala

305 310 315 320

Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly

325 330 335

Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr

340 345 350

Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro

355 360 365

Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln

370 375 380

Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro

385 390 395 400

Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp

405 410 415

Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met

420 425 430

Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn

435 440 445

Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu

450 455 460

Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile

465 470 475 480

Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile

485 490 495

Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val

500 505 510

Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr

515 520 525

Leu Thr Arg Pro Leu

530

<210> 42

<211> 534

<212> PRT

<213> 人工序列

<220>

<223> AAV214A VP3

<400> 42

Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly

50 55 60

Gly Ser Ser Asn Asp Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly

65 70 75 80

Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp

85 90 95

Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn

100 105 110

Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly

115 120 125

Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr

130 135 140

Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly

145 150 155 160

Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly

165 170 175

Tyr Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser Phe

180 185 190

Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn

195 200 205

Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr

210 215 220

Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln

225 230 235 240

Tyr Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln

245 250 255

Gln Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln

260 265 270

Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser

275 280 285

Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly

290 295 300

Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly Pro

305 310 315 320

Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser

325 330 335

Gly Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp

340 345 350

Tyr Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn

355 360 365

Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln

370 375 380

Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu

385 390 395 400

Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile

405 410 415

Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu

420 425 430

Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys

435 440 445

Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys

450 455 460

Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu

465 470 475 480

Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu

485 490 495

Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala

500 505 510

Val Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr Arg

515 520 525

Tyr Leu Thr Arg Pro Leu

530

<210> 43

<211> 533

<212> PRT

<213> 人工序列

<220>

<223> AAV214E VP3

<400> 43

Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly

50 55 60

Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr

65 70 75 80

Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln

85 90 95

Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe

100 105 110

Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val

115 120 125

Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp

130 135 140

Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys

145 150 155 160

Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr

165 170 175

Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr

180 185 190

Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe

195 200 205

Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala

210 215 220

His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr

225 230 235 240

Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln

245 250 255

Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala

260 265 270

Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr

275 280 285

Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr

290 295 300

Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala

305 310 315 320

Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly

325 330 335

Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr

340 345 350

Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro

355 360 365

Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln

370 375 380

Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro

385 390 395 400

Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp

405 410 415

Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met

420 425 430

Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn

435 440 445

Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu

450 455 460

Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile

465 470 475 480

Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile

485 490 495

Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val

500 505 510

Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr

515 520 525

Leu Thr Arg Pro Leu

530

<210> 44

<211> 533

<212> PRT

<213> 人工序列

<220>

<223> AAV214E8 VP3

<400> 44

Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly

50 55 60

Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr

65 70 75 80

Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln

85 90 95

Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe

100 105 110

Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val

115 120 125

Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp

130 135 140

Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys

145 150 155 160

Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr

165 170 175

Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr

180 185 190

Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe

195 200 205

Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala

210 215 220

His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr

225 230 235 240

Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln

245 250 255

Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala

260 265 270

Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr

275 280 285

Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr

290 295 300

Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala

305 310 315 320

Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly

325 330 335

Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr

340 345 350

Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro

355 360 365

Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln

370 375 380

Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro

385 390 395 400

Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp

405 410 415

Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met

420 425 430

Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn

435 440 445

Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu

450 455 460

Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile

465 470 475 480

Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile

485 490 495

Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val

500 505 510

Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr

515 520 525

Leu Thr Arg Pro Leu

530

<210> 45

<211> 533

<212> PRT

<213> 人工序列

<220>

<223> AAV214E9 VP3

<400> 45

Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly

50 55 60

Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr

65 70 75 80

Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln

85 90 95

Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe

100 105 110

Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val

115 120 125

Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp

130 135 140

Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys

145 150 155 160

Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr

165 170 175

Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr

180 185 190

Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe

195 200 205

Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala

210 215 220

His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr

225 230 235 240

Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln

245 250 255

Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala

260 265 270

Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr

275 280 285

Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr

290 295 300

Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala

305 310 315 320

Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly

325 330 335

Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr

340 345 350

Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro

355 360 365

Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln

370 375 380

Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro

385 390 395 400

Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp

405 410 415

Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met

420 425 430

Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn

435 440 445

Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu

450 455 460

Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile

465 470 475 480

Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile

485 490 495

Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val

500 505 510

Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr

515 520 525

Leu Thr Arg Pro Leu

530

<210> 46

<211> 533

<212> PRT

<213> 人工序列

<220>

<223> AAV214E10 VP3

<400> 46

Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly

50 55 60

Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr

65 70 75 80

Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln

85 90 95

Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe

100 105 110

Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val

115 120 125

Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp

130 135 140

Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys

145 150 155 160

Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr

165 170 175

Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr

180 185 190

Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe

195 200 205

Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala

210 215 220

His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr

225 230 235 240

Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln

245 250 255

Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala

260 265 270

Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr

275 280 285

Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr

290 295 300

Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala

305 310 315 320

Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly

325 330 335

Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr

340 345 350

Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro

355 360 365

Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln

370 375 380

Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro

385 390 395 400

Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp

405 410 415

Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met

420 425 430

Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn

435 440 445

Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu

450 455 460

Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile

465 470 475 480

Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile

485 490 495

Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val

500 505 510

Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr

515 520 525

Leu Thr Arg Pro Leu

530

<210> 47

<211> 2211

<212> DNA

<213> 人工序列

<220>

<223> ITB102 45 VP1

<400> 47

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg cgctgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga accttttggt ctggttgagg aaggtgctaa gacggctcct 420

ggaaagaaac gtccggtaga gcagtcgcca caagagccag actcctcctc gggcatcggc 480

aagacaggcc agcagcccgc taaaaagaga ctcaattttg gtcagactgg cgactcagag 540

tcagtccccg acccacaacc tctcggagaa cctccagcaa cccccgctgc tgtgggacct 600

actacaatgg cttcaggcgg tggcgcacca atggcggaca ataacgaagg cgccgacgga 660

gtgggtaatg cctcaggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc 720

accaccagca cccgcacctg ggccttgccc acctacaata accacctcta caagcaaatc 780

tccagtgctt caacgggggc cagcaacgac aaccactact tcggctacag caccccctgg 840

gggtattttg acttcaacag attccactgc cacttttcac cacgtgactg gcaaagactc 900

atcaacaaca actggggatt ccgacccaag agactcaact tcaagctctt taacattcaa 960

gtcaaagagg ttacggacaa caatggagtc aagaccatcg ccaataacct taccagcacg 1020

gtccaggtct tcacggactc agactatcag ctcccgtacg tgctcgggtc ggctcacgag 1080

ggctgcctcc cgccgttccc agcggacgtt ttcatgattc ctcagtacgg ctacctaacg 1140

ctcaacaatg gcagccaggc agtgggacgg tcatcctttt actgcctgga atatttccca 1200

tcgcagatgc tgagaacggg caacaacttt accttcagct acacctttga ggacgttcct 1260

ttccacagca gctacgctca cagccagagt ctggaccggc tgatgaatcc tctgattgac 1320

cagtacctgt actacttgtc tcggactcaa acaacaggag gcacggcaaa tacgcagact 1380

ctgggcttca gccaaggtgg gcctaataca atggccaatc aggcaaagaa ctggctgcca 1440

ggaccctgtt accgccaaca acgcgtctca acgacaaccg ggcaaaacaa caatagcaac 1500

tttgcctgga ctgctgggac caaataccat ctgaatggaa gaaattcatt gatgaatcct 1560

ggccccgcta tggcatccca caaagagggc gaggaccgtt tttttcccct gtccgggtcc 1620

ctgatttttg gcaaacaagg cactggcaga gacaatgtgg atgccgacaa agtcatgatc 1680

accaacgagg aagaaatcaa aaccactaac cctgtggcta cagaggaata cggtatcgtg 1740

gcagataact tgcagcagca aaacacggct cctcaaattg gaactgtcaa cagccagggg 1800

gccttacccg gtatggtctg gcagaaccgg gacgtgtacc tgcagggtcc catctgggcc 1860

aagattcctc acacggacgg caacttccac ccgtctccgc tgatgggcgg ctttggcctg 1920

aaacatcctc cgcctcagat cctgatcaag aacacgcctg tacctgcgga tcctccgacc 1980

accttcaacc agtcaaagct gaactctttc atcacgcaat acagcaccgg acaggtcagc 2040

gtggaaattg aatgggagct gcagaaggaa aacagcaagc gctggaaccc cgagatccag 2100

tacacctcca actactacaa atctacaagt gtggactttg ctgttaatac agaaggcgtg 2160

tactctgaac cccaccccat tggcacccgt tacctcaccc gtcccctgta a 2211

<210> 48

<211> 1605

<212> DNA

<213> 人工序列

<220>

<223> ITB102 45 VP3

<400> 48

atggcttcag gcggtggcgc accaatggcg gacaataacg aaggcgccga cggagtgggt 60

aatgcctcag gaaattggca ttgcgattcc acatggctgg gcgacagagt catcaccacc 120

agcacccgca cctgggcctt gcccacctac aataaccacc tctacaagca aatctccagt 180

gcttcaacgg gggccagcaa cgacaaccac tacttcggct acagcacccc ctgggggtat 240

tttgacttca acagattcca ctgccacttt tcaccacgtg actggcaaag actcatcaac 300

aacaactggg gattccgacc caagagactc aacttcaagc tctttaacat tcaagtcaaa 360

gaggttacgg acaacaatgg agtcaagacc atcgccaata accttaccag cacggtccag 420

gtcttcacgg actcagacta tcagctcccg tacgtgctcg ggtcggctca cgagggctgc 480

ctcccgccgt tcccagcgga cgttttcatg attcctcagt acggctacct aacgctcaac 540

aatggcagcc aggcagtggg acggtcatcc ttttactgcc tggaatattt cccatcgcag 600

atgctgagaa cgggcaacaa ctttaccttc agctacacct ttgaggacgt tcctttccac 660

agcagctacg ctcacagcca gagtctggac cggctgatga atcctctgat tgaccagtac 720

ctgtactact tgtctcggac tcaaacaaca ggaggcacgg caaatacgca gactctgggc 780

ttcagccaag gtgggcctaa tacaatggcc aatcaggcaa agaactggct gccaggaccc 840

tgttaccgcc aacaacgcgt ctcaacgaca accgggcaaa acaacaatag caactttgcc 900

tggactgctg ggaccaaata ccatctgaat ggaagaaatt cattgatgaa tcctggcccc 960

gctatggcat cccacaaaga gggcgaggac cgtttttttc ccctgtccgg gtccctgatt 1020

tttggcaaac aaggcactgg cagagacaat gtggatgccg acaaagtcat gatcaccaac 1080

gaggaagaaa tcaaaaccac taaccctgtg gctacagagg aatacggtat cgtggcagat 1140

aacttgcagc agcaaaacac ggctcctcaa attggaactg tcaacagcca gggggcctta 1200

cccggtatgg tctggcagaa ccgggacgtg tacctgcagg gtcccatctg ggccaagatt 1260

cctcacacgg acggcaactt ccacccgtct ccgctgatgg gcggctttgg cctgaaacat 1320

cctccgcctc agatcctgat caagaacacg cctgtacctg cggatcctcc gaccaccttc 1380

aaccagtcaa agctgaactc tttcatcacg caatacagca ccggacaggt cagcgtggaa 1440

attgaatggg agctgcagaa ggaaaacagc aagcgctgga accccgagat ccagtacacc 1500

tccaactact acaaatctac aagtgtggac tttgctgtta atacagaagg cgtgtactct 1560

gaaccccacc ccattggcac ccgttacctc acccgtcccc tgtaa 1605

<210> 49

<211> 736

<212> PRT

<213> 人工序列

<220>

<223> ITB102 45 VP1

<400> 49

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Phe Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His

260 265 270

Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe

275 280 285

His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn

290 295 300

Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln

305 310 315 320

Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn Asn

325 330 335

Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu Pro

340 345 350

Tyr Val Leu Gly Ser Ala His Glu Gly Cys Leu Pro Pro Phe Pro Ala

355 360 365

Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly

370 375 380

Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro

385 390 395 400

Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe

405 410 415

Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp

420 425 430

Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg

435 440 445

Thr Gln Thr Thr Gly Gly Thr Ala Asn Thr Gln Thr Leu Gly Phe Ser

450 455 460

Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln Asn

485 490 495

Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu Asn

500 505 510

Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys

515 520 525

Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly

530 535 540

Lys Gln Gly Thr Gly Arg Asp Asn Val Asp Ala Asp Lys Val Met Ile

545 550 555 560

Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Glu

565 570 575

Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln

580 585 590

Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn

690 695 700

Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly Val

705 710 715 720

Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 50

<211> 599

<212> PRT

<213> 人工序列

<220>

<223> ITB102 45 VP2

<400> 50

Met Ala Pro Gly Lys Lys Arg Pro Val Glu Gln Ser Pro Gln Glu Pro

1 5 10 15

Asp Ser Ser Ser Gly Ile Gly Lys Thr Gly Gln Gln Pro Ala Lys Lys

20 25 30

Arg Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu Ser Val Pro Asp Pro

35 40 45

Gln Pro Leu Gly Glu Pro Pro Ala Thr Pro Ala Ala Val Gly Pro Thr

50 55 60

Thr Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly

65 70 75 80

Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr

85 90 95

Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu

100 105 110

Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr

115 120 125

Gly Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly

130 135 140

Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp

145 150 155 160

Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn

165 170 175

Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly

180 185 190

Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr

195 200 205

Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Glu Gly

210 215 220

Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly

225 230 235 240

Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe

245 250 255

Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn

260 265 270

Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr

275 280 285

Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln

290 295 300

Tyr Leu Tyr Tyr Leu Ser Arg Thr Gln Thr Thr Gly Gly Thr Ala Asn

305 310 315 320

Thr Gln Thr Leu Gly Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn

325 330 335

Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val

340 345 350

Ser Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala

355 360 365

Gly Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly

370 375 380

Pro Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu

385 390 395 400

Ser Gly Ser Leu Ile Phe Gly Lys Gln Gly Thr Gly Arg Asp Asn Val

405 410 415

Asp Ala Asp Lys Val Met Ile Thr Asn Glu Glu Glu Ile Lys Thr Thr

420 425 430

Asn Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln

435 440 445

Gln Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala

450 455 460

Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro

465 470 475 480

Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro

485 490 495

Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile

500 505 510

Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser

515 520 525

Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val

530 535 540

Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro

545 550 555 560

Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe

565 570 575

Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr

580 585 590

Arg Tyr Leu Thr Arg Pro Leu

595

<210> 51

<211> 534

<212> PRT

<213> 人工序列

<220>

<223> ITB102 45 VP3

<400> 51

Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly

50 55 60

Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr

65 70 75 80

Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln

85 90 95

Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe

100 105 110

Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val

115 120 125

Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp

130 135 140

Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Glu Gly Cys

145 150 155 160

Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr

165 170 175

Leu Thr Leu Asn Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr

180 185 190

Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe

195 200 205

Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala

210 215 220

His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr

225 230 235 240

Leu Tyr Tyr Leu Ser Arg Thr Gln Thr Thr Gly Gly Thr Ala Asn Thr

245 250 255

Gln Thr Leu Gly Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln

260 265 270

Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser

275 280 285

Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly

290 295 300

Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly Pro

305 310 315 320

Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser

325 330 335

Gly Ser Leu Ile Phe Gly Lys Gln Gly Thr Gly Arg Asp Asn Val Asp

340 345 350

Ala Asp Lys Val Met Ile Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn

355 360 365

Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln

370 375 380

Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu

385 390 395 400

Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile

405 410 415

Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu

420 425 430

Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys

435 440 445

Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys

450 455 460

Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu

465 470 475 480

Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu

485 490 495

Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala

500 505 510

Val Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr Arg

515 520 525

Tyr Leu Thr Arg Pro Leu

530

<210> 52

<211> 7

<212> PRT

<213> 人工序列

<220>

<223> VR-I

<400> 52

Ser Ala Ser Thr Gly Ala Ser

1 5

<210> 53

<211> 8

<212> PRT

<213> 人工序列

<220>

<223> VR-I

<400> 53

Asn Ser Thr Ser Gly Gly Ser Ser

1 5

<210> 54

<211> 6

<212> PRT

<213> 人工序列

<220>

<223> VR-II

<400> 54

Asp Asn Asn Gly Val Lys

1 5

<210> 55

<211> 4

<212> PRT

<213> 人工序列

<220>

<223> VR-III

<400> 55

Asn Asp Gly Ser

1

<210> 56

<211> 10

<212> PRT

<213> 人工序列

<220>

<223> VR-IV

<400> 56

Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr

1 5 10

<210> 57

<211> 18

<212> PRT

<213> 人工序列

<220>

<223> VR-V

<400> 57

Arg Val Ser Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp

1 5 10 15

Thr Ala

<210> 58

<211> 13

<212> PRT

<213> 人工序列

<220>

<223> VR-VI

<400> 58

His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly

1 5 10

<210> 59

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> VR-VII

<400> 59

Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val

1 5 10

<210> 60

<211> 13

<212> PRT

<213> 人工序列

<220>

<223> VR-VIII

<400> 60

Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln Ile

1 5 10

<210> 61

<211> 10

<212> PRT

<213> 人工序列

<220>

<223> VR-IX

<400> 61

Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe

1 5 10

<210> 62

<211> 2211

<212> DNA

<213> 人工序列

<220>

<223> AAV6 VP1

<400> 62

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggatgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaaga gggttctcga accttttggt ctggttgagg aaggtgctaa gacggctcct 420

ggaaagaaac gtccggtaga gcagtcgcca caagagccag actcctcctc gggcattggc 480

aagacaggcc agcagcccgc taaaaagaga ctcaattttg gtcagactgg cgactcagag 540

tcagtccccg acccacaacc tctcggagaa cctccagcaa cccccgctgc tgtgggacct 600

actacaatgg cttcaggcgg tggcgcacca atggcagaca ataacgaagg cgccgacgga 660

gtgggtaatg cctcaggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc 720

accaccagca cccgaacatg ggccttgccc acctataaca accacctcta caagcaaatc 780

tccagtgctt caacgggggc cagcaacgac aaccactact tcggctacag caccccctgg 840

gggtattttg atttcaacag attccactgc catttctcac cacgtgactg gcagcgactc 900

atcaacaaca attggggatt ccggcccaag agactcaact tcaagctctt caacatccaa 960

gtcaaggagg tcacgacgaa tgatggcgtc acgaccatcg ctaataacct taccagcacg 1020

gttcaagtct tctcggactc ggagtaccag ttgccgtacg tcctcggctc tgcgcaccag 1080

ggctgcctcc ctccgttccc ggcggacgtg ttcatgattc cgcagtacgg ctacctaacg 1140

ctcaacaatg gcagccaggc agtgggacgg tcatcctttt actgcctgga atatttccca 1200

tcgcagatgc tgagaacggg caataacttt accttcagct acaccttcga ggacgtgcct 1260

ttccacagca gctacgcgca cagccagagc ctggaccggc tgatgaatcc tctcatcgac 1320

cagtacctgt attacctgaa cagaactcag aatcagtccg gaagtgccca aaacaaggac 1380

ttgctgttta gccgggggtc tccagctggc atgtctgttc agcccaaaaa ctggctacct 1440

ggaccctgtt accggcagca gcgcgtttct aaaacaaaaa cagacaacaa caacagcaac 1500

tttacctgga ctggtgcttc aaaatataac cttaatgggc gtgaatctat aatcaaccct 1560

ggcactgcta tggcctcaca caaagacgac aaagacaagt tctttcccat gagcggtgtc 1620

atgatttttg gaaaggagag cgccggagct tcaaacactg cattggacaa tgtcatgatc 1680

acagacgaag aggaaatcaa agccactaac cccgtggcca ccgaaagatt tgggactgtg 1740

gcagtcaatc tccagagcag cagcacagac cctgcgaccg gagatgtgca tgttatggga 1800

gccttacctg gaatggtgtg gcaagacaga gacgtatacc tgcagggtcc tatttgggcc 1860

aaaattcctc acacggatgg acactttcac ccgtctcctc tcatgggcgg ctttggactt 1920

aagcacccgc ctcctcagat cctcatcaaa aacacgcctg ttcctgcgaa tcctccggca 1980

gagttttcgg ctacaaagtt tgcttcattc atcacccagt attccacagg acaagtgagc 2040

gtggagattg aatgggagct gcagaaagaa aacagcaaac gctggaatcc cgaagtgcag 2100

tatacatcta actatgcaaa atctgccaac gttgatttca ctgtggacaa caatggactt 2160

tatactgagc ctcgccccat tggcacccgt tacctcaccc gtcccctgta a 2211

<210> 63

<211> 736

<212> PRT

<213> 人工序列

<220>

<223> AAV6 VP1

<400> 63

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Phe Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His

260 265 270

Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe

275 280 285

His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn

290 295 300

Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln

305 310 315 320

Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn

325 330 335

Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro

340 345 350

Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala

355 360 365

Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly

370 375 380

Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro

385 390 395 400

Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe

405 410 415

Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp

420 425 430

Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg

435 440 445

Thr Gln Asn Gln Ser Gly Ser Ala Gln Asn Lys Asp Leu Leu Phe Ser

450 455 460

Arg Gly Ser Pro Ala Gly Met Ser Val Gln Pro Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Lys Thr Asp Asn

485 490 495

Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Ser Lys Tyr Asn Leu Asn

500 505 510

Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr Ala Met Ala Ser His Lys

515 520 525

Asp Asp Lys Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Gly

530 535 540

Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val Met Ile

545 550 555 560

Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Arg

565 570 575

Phe Gly Thr Val Ala Val Asn Leu Gln Ser Ser Ser Thr Asp Pro Ala

580 585 590

Thr Gly Asp Val His Val Met Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Val Gln Tyr Thr Ser Asn

690 695 700

Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn Gly Leu

705 710 715 720

Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 64

<211> 599

<212> PRT

<213> 人工序列

<220>

<223> AAV6 VP2

<400> 64

Thr Ala Pro Gly Lys Lys Arg Pro Val Glu Gln Ser Pro Gln Glu Pro

1 5 10 15

Asp Ser Ser Ser Gly Ile Gly Lys Thr Gly Gln Gln Pro Ala Lys Lys

20 25 30

Arg Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu Ser Val Pro Asp Pro

35 40 45

Gln Pro Leu Gly Glu Pro Pro Ala Thr Pro Ala Ala Val Gly Pro Thr

50 55 60

Thr Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly

65 70 75 80

Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr

85 90 95

Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu

100 105 110

Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr

115 120 125

Gly Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly

130 135 140

Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp

145 150 155 160

Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn

165 170 175

Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Thr Asn Asp Gly

180 185 190

Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Ser

195 200 205

Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly

210 215 220

Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly

225 230 235 240

Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe

245 250 255

Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn

260 265 270

Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr

275 280 285

Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln

290 295 300

Tyr Leu Tyr Tyr Leu Asn Arg Thr Gln Asn Gln Ser Gly Ser Ala Gln

305 310 315 320

Asn Lys Asp Leu Leu Phe Ser Arg Gly Ser Pro Ala Gly Met Ser Val

325 330 335

Gln Pro Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val

340 345 350

Ser Lys Thr Lys Thr Asp Asn Asn Asn Ser Asn Phe Thr Trp Thr Gly

355 360 365

Ala Ser Lys Tyr Asn Leu Asn Gly Arg Glu Ser Ile Ile Asn Pro Gly

370 375 380

Thr Ala Met Ala Ser His Lys Asp Asp Lys Asp Lys Phe Phe Pro Met

385 390 395 400

Ser Gly Val Met Ile Phe Gly Lys Glu Ser Ala Gly Ala Ser Asn Thr

405 410 415

Ala Leu Asp Asn Val Met Ile Thr Asp Glu Glu Glu Ile Lys Ala Thr

420 425 430

Asn Pro Val Ala Thr Glu Arg Phe Gly Thr Val Ala Val Asn Leu Gln

435 440 445

Ser Ser Ser Thr Asp Pro Ala Thr Gly Asp Val His Val Met Gly Ala

450 455 460

Leu Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro

465 470 475 480

Ile Trp Ala Lys Ile Pro His Thr Asp Gly His Phe His Pro Ser Pro

485 490 495

Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile

500 505 510

Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Ala Glu Phe Ser Ala Thr

515 520 525

Lys Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val

530 535 540

Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro

545 550 555 560

Glu Val Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Ala Asn Val Asp Phe

565 570 575

Thr Val Asp Asn Asn Gly Leu Tyr Thr Glu Pro Arg Pro Ile Gly Thr

580 585 590

Arg Tyr Leu Thr Arg Pro Leu

595

<210> 65

<211> 534

<212> PRT

<213> 人工序列

<220>

<223> AAV6 VP3

<400> 65

Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly

50 55 60

Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr

65 70 75 80

Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln

85 90 95

Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe

100 105 110

Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Thr Asn Asp Gly Val

115 120 125

Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Ser Asp

130 135 140

Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys

145 150 155 160

Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr

165 170 175

Leu Thr Leu Asn Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr

180 185 190

Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe

195 200 205

Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala

210 215 220

His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr

225 230 235 240

Leu Tyr Tyr Leu Asn Arg Thr Gln Asn Gln Ser Gly Ser Ala Gln Asn

245 250 255

Lys Asp Leu Leu Phe Ser Arg Gly Ser Pro Ala Gly Met Ser Val Gln

260 265 270

Pro Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser

275 280 285

Lys Thr Lys Thr Asp Asn Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala

290 295 300

Ser Lys Tyr Asn Leu Asn Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr

305 310 315 320

Ala Met Ala Ser His Lys Asp Asp Lys Asp Lys Phe Phe Pro Met Ser

325 330 335

Gly Val Met Ile Phe Gly Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala

340 345 350

Leu Asp Asn Val Met Ile Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn

355 360 365

Pro Val Ala Thr Glu Arg Phe Gly Thr Val Ala Val Asn Leu Gln Ser

370 375 380

Ser Ser Thr Asp Pro Ala Thr Gly Asp Val His Val Met Gly Ala Leu

385 390 395 400

Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile

405 410 415

Trp Ala Lys Ile Pro His Thr Asp Gly His Phe His Pro Ser Pro Leu

420 425 430

Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys

435 440 445

Asn Thr Pro Val Pro Ala Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys

450 455 460

Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu

465 470 475 480

Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu

485 490 495

Val Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr

500 505 510

Val Asp Asn Asn Gly Leu Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg

515 520 525

Tyr Leu Thr Arg Pro Leu

530

<210> 66

<211> 2217

<212> DNA

<213> 人工序列

<220>

<223> AAV8 VP1

<400> 66

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg cgctgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctgc aggcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gaccggtaga gccatcaccc cagcgttctc cagactcctc tacgggcatc 480

ggcaagaaag gccaacagcc cgccagaaaa agactcaatt ttggtcagac tggcgactca 540

gagtcagttc cagaccctca acctctcgga gaacctccag cagcgccctc tggtgtggga 600

cctaatacaa tggctgcagg cggtggcgca ccaatggcag acaataacga aggcgccgac 660

ggagtgggta gttcctcggg aaattggcat tgcgattcca catggctggg cgacagagtc 720

atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780

atctccaacg ggacatcggg aggagccacc aacgacaaca cctacttcgg ctacagcacc 840

ccctgggggt attttgactt taacagattc cactgccact tttcaccacg tgactggcag 900

cgactcatca acaacaactg gggattccgg cccaagagac tcagcttcaa gctcttcaac 960

atccaggtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taacctcacc 1020

agcaccatcc aggtgtttac ggactcggag taccagctgc cgtacgttct cggctctgcc 1080

caccagggct gcctgcctcc gttcccggcg gacgtgttca tgattcccca gtacggctac 1140

ctaacactca acaacggtag tcaggccgtg ggacgctcct ccttctactg cctggaatac 1200

tttccttcgc agatgctgag aaccggcaac aacttccagt ttacttacac cttcgaggac 1260

gtgcctttcc acagcagcta cgcccacagc cagagcttgg accggctgat gaatcctctg 1320

attgaccagt acctgtacta cttgtctcgg actcaaacaa caggaggcac ggcaaatacg 1380

cagactctgg gcttcagcca aggtgggcct aatacaatgg ccaatcaggc aaagaactgg 1440

ctgccaggac cctgttaccg ccaacaacgc gtctcaacga caaccgggca aaacaacaat 1500

agcaactttg cctggactgc tgggaccaaa taccatctga atggaagaaa ttcattggct 1560

aatcctggca tcgctatggc aacacacaaa gacgacgagg agcgtttttt tcccagtaac 1620

gggatcctga tttttggcaa acaaaatgct gccagagaca atgcggatta cagcgatgtc 1680

atgctcacca gcgaggaaga aatcaaaacc actaaccctg tggctacaga ggaatacggt 1740

atcgtggcag ataacttgca gcagcaaaac acggctcctc aaattggaac tgtcaacagc 1800

cagggggcct tacccggtat ggtctggcag aaccgggacg tgtacctgca gggtcccatc 1860

tgggccaaga ttcctcacac ggacggcaac ttccacccgt ctccgctgat gggcggcttt 1920

ggcctgaaac atcctccgcc tcagatcctg atcaagaaca cgcctgtacc tgcggatcct 1980

ccgaccacct tcaaccagtc aaagctgaac tctttcatca cgcaatacag caccggacag 2040

gtcagcgtgg aaattgaatg ggagctgcag aaggaaaaca gcaagcgctg gaaccccgag 2100

atccagtaca cctccaacta ctacaaatct acaagtgtgg actttgctgt taatacagaa 2160

ggcgtgtact ctgaaccccg ccccattggc acccgttacc tcacccgtaa tctgtaa 2217

<210> 67

<211> 738

<212> PRT

<213> 人工序列

<220>

<223> AAV8 VP1

<400> 67

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Gln Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile

145 150 155 160

Gly Lys Lys Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln

165 170 175

Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro

180 185 190

Pro Ala Ala Pro Ser Gly Val Gly Pro Asn Thr Met Ala Ala Gly Gly

195 200 205

Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser

210 215 220

Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val

225 230 235 240

Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His

245 250 255

Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ala Thr Asn Asp

260 265 270

Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn

275 280 285

Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn

290 295 300

Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn

305 310 315 320

Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala

325 330 335

Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln

340 345 350

Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe

355 360 365

Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn

370 375 380

Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr

385 390 395 400

Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Thr Tyr

405 410 415

Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser

420 425 430

Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu

435 440 445

Ser Arg Thr Gln Thr Thr Gly Gly Thr Ala Asn Thr Gln Thr Leu Gly

450 455 460

Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp

465 470 475 480

Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly

485 490 495

Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His

500 505 510

Leu Asn Gly Arg Asn Ser Leu Ala Asn Pro Gly Ile Ala Met Ala Thr

515 520 525

His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Asn Gly Ile Leu Ile

530 535 540

Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val

545 550 555 560

Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr

565 570 575

Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala

580 585 590

Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val

595 600 605

Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile

610 615 620

Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe

625 630 635 640

Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val

645 650 655

Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe

660 665 670

Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu

675 680 685

Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr

690 695 700

Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu

705 710 715 720

Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg

725 730 735

Asn Leu

<210> 68

<211> 601

<212> PRT

<213> 人工序列

<220>

<223> AAV8 VP2

<400> 68

Met Ala Pro Gly Lys Lys Arg Pro Val Glu Pro Ser Pro Gln Arg Ser

1 5 10 15

Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gln Gln Pro Ala Arg

20 25 30

Lys Arg Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu Ser Val Pro Asp

35 40 45

Pro Gln Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser Gly Val Gly Pro

50 55 60

Asn Thr Met Ala Ala Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu

65 70 75 80

Gly Ala Asp Gly Val Gly Ser Ser Ser Gly Asn Trp His Cys Asp Ser

85 90 95

Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala

100 105 110

Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Asn Gly Thr

115 120 125

Ser Gly Gly Ala Thr Asn Asp Asn Thr Tyr Phe Gly Tyr Ser Thr Pro

130 135 140

Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg

145 150 155 160

Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg

165 170 175

Leu Ser Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Gln Asn

180 185 190

Glu Gly Thr Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile Gln Val

195 200 205

Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His

210 215 220

Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln

225 230 235 240

Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ala Val Gly Arg Ser

245 250 255

Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly

260 265 270

Asn Asn Phe Gln Phe Thr Tyr Thr Phe Glu Asp Val Pro Phe His Ser

275 280 285

Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile

290 295 300

Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr Gln Thr Thr Gly Gly Thr

305 310 315 320

Ala Asn Thr Gln Thr Leu Gly Phe Ser Gln Gly Gly Pro Asn Thr Met

325 330 335

Ala Asn Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln

340 345 350

Arg Val Ser Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp

355 360 365

Thr Ala Gly Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Ala Asn

370 375 380

Pro Gly Ile Ala Met Ala Thr His Lys Asp Asp Glu Glu Arg Phe Phe

385 390 395 400

Pro Ser Asn Gly Ile Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp

405 410 415

Asn Ala Asp Tyr Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys

420 425 430

Thr Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn

435 440 445

Leu Gln Gln Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln

450 455 460

Gly Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln

465 470 475 480

Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro

485 490 495

Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile

500 505 510

Leu Ile Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn

515 520 525

Gln Ser Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val

530 535 540

Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp

545 550 555 560

Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val

565 570 575

Asp Phe Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro Arg Pro Ile

580 585 590

Gly Thr Arg Tyr Leu Thr Arg Asn Leu

595 600

<210> 69

<211> 535

<212> PRT

<213> 人工序列

<220>

<223> AAV8 VP3

<400> 69

Met Ala Ala Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Ser Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly

50 55 60

Gly Ala Thr Asn Asp Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly

65 70 75 80

Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp

85 90 95

Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser

100 105 110

Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly

115 120 125

Thr Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr

130 135 140

Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly

145 150 155 160

Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly

165 170 175

Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe

180 185 190

Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn

195 200 205

Phe Gln Phe Thr Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr

210 215 220

Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln

225 230 235 240

Tyr Leu Tyr Tyr Leu Ser Arg Thr Gln Thr Thr Gly Gly Thr Ala Asn

245 250 255

Thr Gln Thr Leu Gly Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn

260 265 270

Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val

275 280 285

Ser Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala

290 295 300

Gly Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Ala Asn Pro Gly

305 310 315 320

Ile Ala Met Ala Thr His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser

325 330 335

Asn Gly Ile Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala

340 345 350

Asp Tyr Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr

355 360 365

Asn Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln

370 375 380

Gln Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala

385 390 395 400

Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro

405 410 415

Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro

420 425 430

Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile

435 440 445

Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser

450 455 460

Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val

465 470 475 480

Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro

485 490 495

Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe

500 505 510

Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr

515 520 525

Arg Tyr Leu Thr Arg Asn Leu

530 535

<210> 70

<211> 2214

<212> DNA

<213> 人工序列

<220>

<223> AAV9 VP1

<400> 70

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg cgctgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacggcaa ggcctacgac 240

cagcagctgc aggcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gaccggtaga gccatcaccc cagcgttctc cagactcctc tacgggcatc 480

ggcaagaaag gccaacagcc cgccagaaaa agactcaatt ttggtcagac tggcgactca 540

gagtcagttc cagaccctca acctctcgga gaacctccag cagcgccctc tggtgtggga 600

cctaatacaa tggctgcagg cggtggcgca ccaatggcag acaataacga aggcgccgac 660

ggagtgggta attcctcggg aaattggcat tgcgattcca catggctggg ggacagagtc 720

atcaccacca gcacccgaac ctgggcattg cccacctaca acaaccacct ctacaagcaa 780

atctccaatg gaacatcggg aggaagcacc aacgacaaca cctactttgg ctacagcacc 840

ccctgggggt attttgactt caacagattc cactgccact tctcaccacg tgactggcag 900

cgactcatca acaacaactg gggattccgg ccaaagagac tcaacttcaa gctgttcaac 960

atccaggtca aggaggttac gacgaacgaa ggcaccaaga ccatcgccaa taaccttacc 1020

agcaccgtcc aggtctttac ggactcggag taccagctac cgtacgtcct aggctctgcc 1080

caccaaggat gcctgccacc gtttcctgca gacgtcttca tggttcctca gtacggctac 1140

ctgacgctca acaatggaag tcaagcgtta ggacgttctt ctttctactg tctggaatac 1200

ttcccttctc agatgctgag aaccggcaac aactttcagt tcagctacac tttcgaggac 1260

gtgcctttcc acagcagcta cgcacacagc cagagtctag atcgactgat gaaccccctc 1320

atcgaccagt acctatacta cctggtcaga acacagacaa ctggaactgg gggaactcaa 1380

actttggcat tcagccaagc aggccctagc tcaatggcca atcaggctag aaactgggta 1440

cccgggcctt gctaccgtca gcagcgcgtc tccacaacca ccaaccaaaa taacaacagc 1500

aactttgcgt ggacgggagc tgctaaattc aagctgaacg ggagagactc gctaatgaat 1560

cctggcgtgg ctatggcatc gcacaaagac gacgaggacc gcttctttcc atcaagtggc 1620

gttctcatat ttggcaagca aggagccggg aacgatggag tcgactacag ccaggtgctg 1680

attacagatg aggaagaaat taaagccacc aaccctgtag ccacagagga atacggagca 1740

gtggccatca acaaccaggc cgctaacacg caggcgcaaa ctggacttgt gcataaccag 1800

ggagttattc ctggtatggt ctggcagaac cgggacgtgt acctgcaggg ccctatttgg 1860

gctaaaatac ctcacacaga tggcaacttt cacccgtctc ctctgatggg tggatttgga 1920

ctgaaacacc cacctccaca gattctaatt aaaaatacac cagtgccggc agatcctcct 1980

cttaccttca atcaagccaa gctgaactct ttcatcacgc agtacagcac gggacaagtc 2040

agcgtggaaa tcgagtggga gctgcagaaa gaaaacagca agcgctggaa tccagagatc 2100

cagtatactt caaactacta caaatctaca aatgtggact ttgctgtcaa taccaaaggt 2160

gtttactctg agcctcgccc cattggtact cgttacctca cccgtaattt gtaa 2214

<210> 71

<211> 736

<212> PRT

<213> 人工序列

<220>

<223> AAV9 VP1

<400> 71

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Gln Pro

20 25 30

Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro

115 120 125

Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ala Gly Ile Gly

145 150 155 160

Lys Ser Gly Ala Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro

180 185 190

Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn

260 265 270

Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Glu Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp

370 375 380

Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Glu

405 410 415

Phe Glu Asn Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser

435 440 445

Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser

450 455 460

Val Ala Gly Pro Ser Asn Met Ala Val Gln Gly Arg Asn Tyr Ile Pro

465 470 475 480

Gly Pro Ser Tyr Arg Gln Gln Arg Val Ser Thr Thr Val Thr Gln Asn

485 490 495

Asn Asn Ser Glu Phe Ala Trp Pro Gly Ala Ser Ser Trp Ala Leu Asn

500 505 510

Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys

515 520 525

Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly

530 535 540

Lys Gln Gly Thr Gly Arg Asp Asn Val Asp Ala Asp Lys Val Met Ile

545 550 555 560

Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Ser

565 570 575

Tyr Gly Gln Val Ala Thr Asn His Gln Ser Ala Gln Ala Gln Ala Gln

580 585 590

Thr Gly Trp Val Gln Asn Gln Gly Ile Leu Pro Gly Met Val Trp Gln

595 600 605

Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Met

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asp Pro Pro Thr Ala Phe Asn Lys Asp Lys Leu Asn Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn

690 695 700

Tyr Tyr Lys Ser Asn Asn Val Glu Phe Ala Val Asn Thr Glu Gly Val

705 710 715 720

Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu

725 730 735

<210> 72

<211> 599

<212> PRT

<213> 人工序列

<220>

<223> AAV9 VP2

<400> 72

Met Ala Pro Gly Lys Lys Arg Pro Val Glu Gln Ser Pro Gln Glu Pro

1 5 10 15

Asp Ser Ser Ala Gly Ile Gly Lys Ser Gly Ala Gln Pro Ala Lys Lys

20 25 30

Arg Leu Asn Phe Gly Gln Thr Gly Asp Thr Glu Ser Val Pro Asp Pro

35 40 45

Gln Pro Ile Gly Glu Pro Pro Ala Ala Pro Ser Gly Val Gly Ser Leu

50 55 60

Thr Met Ala Ser Gly Gly Gly Ala Pro Val Ala Asp Asn Asn Glu Gly

65 70 75 80

Ala Asp Gly Val Gly Ser Ser Ser Gly Asn Trp His Cys Asp Ser Gln

85 90 95

Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu

100 105 110

Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Asn Ser Thr Ser

115 120 125

Gly Gly Ser Ser Asn Asp Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp

130 135 140

Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp

145 150 155 160

Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu

165 170 175

Asn Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn

180 185 190

Gly Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe

195 200 205

Thr Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Glu

210 215 220

Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr

225 230 235 240

Gly Tyr Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser

245 250 255

Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn

260 265 270

Asn Phe Gln Phe Ser Tyr Glu Phe Glu Asn Val Pro Phe His Ser Ser

275 280 285

Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp

290 295 300

Gln Tyr Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn

305 310 315 320

Gln Gln Thr Leu Lys Phe Ser Val Ala Gly Pro Ser Asn Met Ala Val

325 330 335

Gln Gly Arg Asn Tyr Ile Pro Gly Pro Ser Tyr Arg Gln Gln Arg Val

340 345 350

Ser Thr Thr Val Thr Gln Asn Asn Asn Ser Glu Phe Ala Trp Pro Gly

355 360 365

Ala Ser Ser Trp Ala Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly

370 375 380

Pro Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu

385 390 395 400

Ser Gly Ser Leu Ile Phe Gly Lys Gln Gly Thr Gly Arg Asp Asn Val

405 410 415

Asp Ala Asp Lys Val Met Ile Thr Asn Glu Glu Glu Ile Lys Thr Thr

420 425 430

Asn Pro Val Ala Thr Glu Ser Tyr Gly Gln Val Ala Thr Asn His Gln

435 440 445

Ser Ala Gln Ala Gln Ala Gln Thr Gly Trp Val Gln Asn Gln Gly Ile

450 455 460

Leu Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro

465 470 475 480

Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro

485 490 495

Leu Met Gly Gly Phe Gly Met Lys His Pro Pro Pro Gln Ile Leu Ile

500 505 510

Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Ala Phe Asn Lys Asp

515 520 525

Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val

530 535 540

Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro

545 550 555 560

Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Asn Asn Val Glu Phe

565 570 575

Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr

580 585 590

Arg Tyr Leu Thr Arg Asn Leu

595

<210> 73

<211> 534

<212> PRT

<213> 人工序列

<220>

<223> AAV9 VP3

<400> 73

Met Ala Ser Gly Gly Gly Ala Pro Val Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Ser Ser Ser Gly Asn Trp His Cys Asp Ser Gln Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly

50 55 60

Gly Ser Ser Asn Asp Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly

65 70 75 80

Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp

85 90 95

Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn

100 105 110

Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly

115 120 125

Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr

130 135 140

Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Glu Gly

145 150 155 160

Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly

165 170 175

Tyr Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser Phe

180 185 190

Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn

195 200 205

Phe Gln Phe Ser Tyr Glu Phe Glu Asn Val Pro Phe His Ser Ser Tyr

210 215 220

Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln

225 230 235 240

Tyr Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln

245 250 255

Gln Thr Leu Lys Phe Ser Val Ala Gly Pro Ser Asn Met Ala Val Gln

260 265 270

Gly Arg Asn Tyr Ile Pro Gly Pro Ser Tyr Arg Gln Gln Arg Val Ser

275 280 285

Thr Thr Val Thr Gln Asn Asn Asn Ser Glu Phe Ala Trp Pro Gly Ala

290 295 300

Ser Ser Trp Ala Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly Pro

305 310 315 320

Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser

325 330 335

Gly Ser Leu Ile Phe Gly Lys Gln Gly Thr Gly Arg Asp Asn Val Asp

340 345 350

Ala Asp Lys Val Met Ile Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn

355 360 365

Pro Val Ala Thr Glu Ser Tyr Gly Gln Val Ala Thr Asn His Gln Ser

370 375 380

Ala Gln Ala Gln Ala Gln Thr Gly Trp Val Gln Asn Gln Gly Ile Leu

385 390 395 400

Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile

405 410 415

Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu

420 425 430

Met Gly Gly Phe Gly Met Lys His Pro Pro Pro Gln Ile Leu Ile Lys

435 440 445

Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Ala Phe Asn Lys Asp Lys

450 455 460

Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu

465 470 475 480

Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu

485 490 495

Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Asn Asn Val Glu Phe Ala

500 505 510

Val Asn Thr Glu Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg

515 520 525

Tyr Leu Thr Arg Asn Leu

530

<210> 74

<211> 6

<212> PRT

<213> 人工序列

<220>

<223> VRII-204/AAV6

<400> 74

Thr Asn Asp Gly Val Lys

1 5

<210> 75

<211> 4

<212> PRT

<213> 人工序列

<220>

<223> VRIII-204/AAV6

<400> 75

Asn Asn Gly Ser

1

<210> 76

<211> 11

<212> PRT

<213> 人工序列

<220>

<223> VRIV-204/AAV6

<400> 76

Gln Asn Gln Ser Gly Ser Ala Gln Asn Lys Asp

1 5 10

<210> 77

<211> 18

<212> PRT

<213> 人工序列

<220>

<223> VRV-204/AAV6

<400> 77

Arg Val Ser Lys Thr Lys Thr Asp Asn Asn Asn Ser Asn Phe Thr Trp

1 5 10 15

Thr Gly

<210> 78

<211> 13

<212> PRT

<213> 人工序列

<220>

<223> VRVI-204/AAV6

<400> 78

His Lys Asp Asp Lys Asp Lys Phe Phe Pro Met Ser Gly

1 5 10

<210> 79

<211> 14

<212> PRT

<213> 人工序列

<220>

<223> VRVII-204/AAV6

<400> 79

Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val

1 5 10

<210> 80

<211> 13

<212> PRT

<213> 人工序列

<220>

<223> VRVIII-204/AAV6

<400> 80

Ala Val Asn Leu Gln Asn Ser Ser Thr Asp Pro Ala Thr

1 5 10

<210> 81

<211> 10

<212> PRT

<213> 人工序列

<220>

<223> VRIX-204/AAV6

<400> 81

Asn Tyr Ala Lys Ser Ala Asn Val Asp Phe

1 5 10

<210> 82

<211> 2211

<212> DNA

<213> 人工序列

<220>

<223> AAV214-AB VP1

<400> 82

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg cgctgaaacc tggagccccg aagcccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga accttttggt ctggttgagg aaggtgctaa gacggctcct 420

ggaaagaaac gtccggtaga gcagtcgcca caagagccag actcctcctc gggcatcggc 480

aagacaggcc agcagcccgc taaaaagaga ctcaattttg gtcagactgg cgactcagag 540

tcagtccccg acccacaacc tctcggagaa cctccagcaa cccccgctgc tgtgggacct 600

actacaatgg cttcaggcgg tggcgcacca atggcggaca ataacgaagg cgccgacgga 660

gtgggtaatg cctcaggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc 720

accaccagca cccgcacctg ggccttgccc acctacaata accacctcta caagcaaatc 780

tccagcagca catctggagg atcttcaaat gacaacgcct acttcggcta cagcaccccc 840

tgggggtatt ttgacttcaa cagattccac tgccactttt caccacgtga ctggcaaaga 900

ctcatcaaca acaactgggg attccgaccc aagagactca acttcaagct ctttaacatt 960

caagtcaaag aggttacgga caacaatgga gtcaagacca tcgccaataa ccttaccagc 1020

acggtccagg tcttcacgga ctcagactat cagctcccgt acgtcctcgg ctctgcgcac 1080

cagggctgcc tccctccgtt cccggcggac gtgttcatga ttccgcagta cggctaccta 1140

acgctcaacg acggcagcca ggcagtggga cggtcatcct tttactgcct ggaatatttc 1200

ccatcgcaga tgctgagaac gggcaacaac tttaccttca gctacacctt tgaggacgtt 1260

cctttccaca gcagctacgc tcacagccag agtctggacc gtctcatgaa tcctctgatt 1320

gaccagtacc tgtactactt gtctaagact atcaacggat ccggccagaa tcagcagact 1380

ctgaagttca gccaaggtgg gcctaataca atggccaatc aggcaaagaa ctggctgcca 1440

ggaccctgtt accgccaaca acgcgtctca acgacaaccg ggcaaaacaa caatagcaac 1500

tttgcctgga ctgctgggac caaataccat ctgaatggaa gaaattcatt gatgaatcct 1560

ggccccgcta tggcatccca caaagagggc gaggaccgtt tttttcccct gtccgggtcc 1620

ctgatttttg gcaaacaaaa tgctgccaga gacaatgcgg attacagcga tgtcatgctc 1680

accagcgagg aagaaatcaa aaccactaac cctgtggcta cagaggaata cggtatcgtg 1740

gcagataact tgcagcagca aaacacggct cctcaaattg gaactgtcaa cagccagggg 1800

gccttacccg gtatggtctg gcagaaccgg gacgtgtacc tgcagggtcc catctgggcc 1860

aagattcctc acacggacgg caacttccac ccgtctccgc tgatgggcgg ctttggcctg 1920

aaacatcctc cgcctcagat cctgatcaag aacacgcctg tacctgcgga tcctccgacc 1980

accttcaacc agtcaaagct gaactctttc atcacgcaat acagcaccgg acaggtcagc 2040

gtggaaattg aatgggagct gcagaaggaa aacagcaagc gctggaaccc cgagatccag 2100

tacacctcca actactacaa atctacaagt gtggactttg ctgttaatac agaaggcgtg 2160

tactctgaac cccaccccat tggcacccgt tacctcaccc gtcccctgta a 2211

<210> 83

<211> 1605

<212> DNA

<213> 人工序列

<220>

<223> AAV214-AB VP3

<400> 83

atggcttcag gcggtggcgc accaatggcg gacaataacg aaggcgccga cggagtgggt 60

aatgcctcag gaaattggca ttgcgattcc acatggctgg gcgacagagt catcaccacc 120

agcacccgca cctgggcctt gcccacctac aataaccacc tctacaagca aatctccagc 180

agcacatctg gaggatcttc aaatgacaac gcctacttcg gctacagcac cccctggggg 240

tattttgact tcaacagatt ccactgccac ttttcaccac gtgactggca aagactcatc 300

aacaacaact ggggattccg acccaagaga ctcaacttca agctctttaa cattcaagtc 360

aaagaggtta cggacaacaa tggagtcaag accatcgcca ataaccttac cagcacggtc 420

caggtcttca cggactcaga ctatcagctc ccgtacgtcc tcggctctgc gcaccagggc 480

tgcctccctc cgttcccggc ggacgtgttc atgattccgc agtacggcta cctaacgctc 540

aacgacggca gccaggcagt gggacggtca tccttttact gcctggaata tttcccatcg 600

cagatgctga gaacgggcaa caactttacc ttcagctaca cctttgagga cgttcctttc 660

cacagcagct acgctcacag ccagagtctg gaccgtctca tgaatcctct gattgaccag 720

tacctgtact acttgtctaa gactatcaac ggatccggcc agaatcagca gactctgaag 780

ttcagccaag gtgggcctaa tacaatggcc aatcaggcaa agaactggct gccaggaccc 840

tgttaccgcc aacaacgcgt ctcaacgaca accgggcaaa acaacaatag caactttgcc 900

tggactgctg ggaccaaata ccatctgaat ggaagaaatt cattgatgaa tcctggcccc 960

gctatggcat cccacaaaga gggcgaggac cgtttttttc ccctgtccgg gtccctgatt 1020

tttggcaaac aaaatgctgc cagagacaat gcggattaca gcgatgtcat gctcaccagc 1080

gaggaagaaa tcaaaaccac taaccctgtg gctacagagg aatacggtat cgtggcagat 1140

aacttgcagc agcaaaacac ggctcctcaa attggaactg tcaacagcca gggggcctta 1200

cccggtatgg tctggcagaa ccgggacgtg tacctgcagg gtcccatctg ggccaagatt 1260

cctcacacgg acggcaactt ccacccgtct ccgctgatgg gcggctttgg cctgaaacat 1320

cctccgcctc agatcctgat caagaacacg cctgtacctg cggatcctcc gaccaccttc 1380

aaccagtcaa agctgaactc tttcatcacg caatacagca ccggacaggt cagcgtggaa 1440

attgaatggg agctgcagaa ggaaaacagc aagcgctgga accccgagat ccagtacacc 1500

tccaactact acaaatctac aagtgtggac tttgctgtta atacagaagg cgtgtactct 1560

gaaccccacc ccattggcac ccgttacctc acccgtcccc tgtaa 1605

<210> 84

<211> 736

<212> PRT

<213> 人工序列

<220>

<223> AAV214AB VP1

<400> 84

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser

1 5 10 15

Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Lys Pro

20 25 30

Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro

35 40 45

Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro

50 55 60

Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp

65 70 75 80

Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala

85 90 95

Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly

100 105 110

Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro

115 120 125

Phe Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg

130 135 140

Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly

145 150 155 160

Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr

165 170 175

Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro

180 185 190

Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly

195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala

210 215 220

Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile

225 230 235 240

Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu

245 250 255

Tyr Lys Gln Ile Ser Ser Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn

260 265 270

Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg

275 280 285

Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn

290 295 300

Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile

305 310 315 320

Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn

325 330 335

Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu

340 345 350

Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro

355 360 365

Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp

370 375 380

Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe

385 390 395 400

Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr

405 410 415

Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu

420 425 430

Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser

435 440 445

Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser

450 455 460

Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu Pro

465 470 475 480

Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln Asn

485 490 495

Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu Asn

500 505 510

Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys

515 520 525

Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly

530 535 540

Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val Met Leu

545 550 555 560

Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Glu

565 570 575

Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln

580 585 590

Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln

595 600 605

Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His

610 615 620

Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu

625 630 635 640

Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala

645 650 655

Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr

660 665 670

Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln

675 680 685

Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn

690 695 700

Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly Val

705 710 715 720

Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu

725 730 735

<210> 85

<211> 599

<212> PRT

<213> 人工序列

<220>

<223> AAV214AB VP2

<400> 85

Met Ala Pro Gly Lys Lys Arg Pro Val Glu Gln Ser Pro Gln Glu Pro

1 5 10 15

Asp Ser Ser Ser Gly Ile Gly Lys Thr Gly Gln Gln Pro Ala Lys Lys

20 25 30

Arg Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu Ser Val Pro Asp Pro

35 40 45

Gln Pro Leu Gly Glu Pro Pro Ala Thr Pro Ala Ala Val Gly Pro Thr

50 55 60

Thr Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly

65 70 75 80

Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr

85 90 95

Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu

100 105 110

Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ser Thr Ser

115 120 125

Gly Gly Ser Ser Asn Asp Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp

130 135 140

Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp

145 150 155 160

Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu

165 170 175

Asn Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn

180 185 190

Gly Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe

195 200 205

Thr Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln

210 215 220

Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr

225 230 235 240

Gly Tyr Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser

245 250 255

Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn

260 265 270

Asn Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser

275 280 285

Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp

290 295 300

Gln Tyr Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn

305 310 315 320

Gln Gln Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn

325 330 335

Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val

340 345 350

Ser Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala

355 360 365

Gly Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly

370 375 380

Pro Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu

385 390 395 400

Ser Gly Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala

405 410 415

Asp Tyr Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr

420 425 430

Asn Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln

435 440 445

Gln Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala

450 455 460

Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro

465 470 475 480

Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro

485 490 495

Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile

500 505 510

Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser

515 520 525

Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val

530 535 540

Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro

545 550 555 560

Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe

565 570 575

Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr

580 585 590

Arg Tyr Leu Thr Arg Pro Leu

595

<210> 86

<211> 534

<212> PRT

<213> 人工序列

<220>

<223> AAV214AB VP3

<400> 86

Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala

1 5 10 15

Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp

20 25 30

Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro

35 40 45

Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ser Thr Ser Gly

50 55 60

Gly Ser Ser Asn Asp Asn Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly

65 70 75 80

Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp

85 90 95

Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn

100 105 110

Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Asp Asn Asn Gly

115 120 125

Val Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Thr

130 135 140

Asp Ser Asp Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly

145 150 155 160

Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly

165 170 175

Tyr Leu Thr Leu Asn Asp Gly Ser Gln Ala Val Gly Arg Ser Ser Phe

180 185 190

Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn

195 200 205

Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr

210 215 220

Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln

225 230 235 240

Tyr Leu Tyr Tyr Leu Ser Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln

245 250 255

Gln Thr Leu Lys Phe Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln

260 265 270

Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser

275 280 285

Thr Thr Thr Gly Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly

290 295 300

Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Met Asn Pro Gly Pro

305 310 315 320

Ala Met Ala Ser His Lys Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser

325 330 335

Gly Ser Leu Ile Phe Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp

340 345 350

Tyr Ser Asp Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn

355 360 365

Pro Val Ala Thr Glu Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln

370 375 380

Gln Asn Thr Ala Pro Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu

385 390 395 400

Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile

405 410 415

Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu

420 425 430

Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys

435 440 445

Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys

450 455 460

Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu

465 470 475 480

Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu

485 490 495

Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala

500 505 510

Val Asn Thr Glu Gly Val Tyr Ser Glu Pro His Pro Ile Gly Thr Arg

515 520 525

Tyr Leu Thr Arg Pro Leu

530

<210> 87

<211> 8

<212> PRT

<213> 人工序列

<220>

<223> AAV214AB VR-1氨基酸

<400> 87

Ser Ser Thr Ser Gly Gly Ser Ser

1 5

<210> 88

<211> 6719

<212> DNA

<213> 人工序列

<220>

<223> pA-CF1

<400> 88

tcctgcaggc agctgcgcgc tcgctcgctc actgaggccg cccgggcaaa gcccgggcgt 60

cgggcgacct ttggtcgccc ggcctcagtg agcgagcgag cgcgcagaga gggagtggcc 120

aactccatca ctaggggttc ctgcggccgc atggaggcgg tactatgtag atgagaattc 180

aggagcaaac tgggaaaagc aactgcttcc aaatatttgt gatttttaca gtgtagtttt 240

ggaaaaactc ttagcctacc aattcttcta agtgttttaa aatgtgggag ccagtacaca 300

tgaagttata gagtgtttta atgaggctta aatatttacc gtaactatga aatgctacgc 360

atatcatgct gttcaggctc cgtggccacg caactcatac cggtagtact cgccaccatg 420

cagagaagcc ccctggagaa ggcctctgtg gtgagcaagc tgttcttcag ctggaccaga 480

cccatcctga gaaagggcta cagacagaga ctggagctgt ctgacatcta ccagatcccc 540

tctgtggact ctgctgacaa cctgtctgag aagctggaga gagagtggga cagagagctg 600

gccagcaaga agaaccccaa gctgatcaat gccctgagaa gatgcttctt ctggagattc 660

atgttctatg gcatcttcct gtacctgggg gaggtgacca aggctgtgca gcccctgctg 720

ctgggcagaa tcattgccag ctatgaccct gacaacaagg aggagagaag cattgccatc 780

tacctgggca ttggcctgtg cctgctgttc attgtgagaa ccctgctgct gcaccctgcc 840

atctttggcc tgcaccacat tggcatgcag atgagaattg ccatgttcag cctgatctac 900

aagaagaccc tgaagctgag cagcagagtg ctggacaaga tcagcattgg ccagctggtg 960

agcctgctga gcaacaacct gaacaagttt gatgagggcc tggccctggc ccactttgtg 1020

tggattgccc ccctgcaggt ggccctgctg atgggcctga tctgggagct gctgcaggcc 1080

tctgccttct gtggcctggg cttcctgatt gtgctggccc tgttccaggc tggcctgggc 1140

agaatgatga tgaagtacag agaccagaga gctggcaaga tctctgagag actggtgatc 1200

acctctgaga tgattgagaa catccagtct gtgaaggcct actgctggga ggaggccatg 1260

gagaagatga ttgagaacct gagacagaca gagctgaagc tgaccagaaa ggctgcctat 1320

gtgagatact tcaacagctc tgccttcttc ttctctggct tctttgtggt gttcctgtct 1380

gtgctgccct atgccctgat caagggcatc atcctgagaa agatcttcac caccatcagc 1440

ttctgcattg tgctgagaat ggctgtgacc agacagttcc cctgggctgt gcagacctgg 1500

tatgacagcc tgggggccat caacaagatc caggacttcc tgcagaagca ggagtacaag 1560

accctggagt acaacctgac caccacagag gtggtgatgg agaatgtgac agccttctgg 1620

gaggagggct ttggggagct gtttgagaag gccaagcaga acaacaacaa cagaaagacc 1680

agcaatgggg atgacagcct gttcttcagc aacttcagcc tgctgggcac ccctgtgctg 1740

aaggacatca acttcaagat tgagagaggc cagctgctgg ctgtggctgg cagcacaggg 1800

gctggcaaga ccagcctgct gatgatgatc atgggggagc tggagccctc tgagggcaag 1860

atcaagcact ctggcagaat cagcttctgc agccagttca gctggatcat gcctggcacc 1920

atcaaggaga acatcatctt tggggtgagc tatgatgagt acagatacag atctgtgatc 1980

aaggcctgcc agctggagga ggacatcagc aagtttgctg agaaggacaa cattgtgctg 2040

ggggaggggg gcatcaccct gtctgggggc cagagagcca gaatcagcct ggccagagct 2100

gtgtacaagg atgctgacct gtacctgctg gacagcccct ttggctacct ggatgtgctg 2160

acagagaagg agatctttga gagctgtgtg tgcaagctga tggccaacaa gaccagaatc 2220

ctggtgacca gcaagatgga gcacctgaag aaggctgaca agatcctgat cctgcatgag 2280

ggcagcagct acttctatgg caccttctct gagctgcaga acctgcagcc tgacttcagc 2340

agcaagctga tgggctgtga cagctttgac cagttctctg ctgagagaag aaacagcatc 2400

ctgacagaga ccctgcacag attcagcctg gagggggatg cccctgtgag ctggacagag 2460

accaagaagc agagcttcaa gcagacaggg gagtttgggg agaagagaaa gaacagcatc 2520

ctgaacccca tcaacagcac cctgcaggcc agaagaagac agtctgtgct gaacctgatg 2580

acccactctg tgaaccaggg ccagaacatc cacagaaaga ccacagccag caccagaaag 2640

gtgagcctgg ccccccaggc caacctgaca gagctggaca tctacagcag aagactgagc 2700

caggagacag gcctggagat ctctgaggag atcaatgagg aggacctgaa ggagtgcttc 2760

tttgatgaca tggagagcat ccctgctgtg accacctgga acacctacct gagatacatc 2820

acagtgcaca agagcctgat ctttgtgctg atctggtgcc tggtgatctt cctggctgag 2880

gtggctgcca gcctggtggt gctgtggctg ctgggcaaca cccccctgca ggacaagggc 2940

aacagcaccc acagcagaaa caacagctat gctgtgatca tcaccagcac cagcagctac 3000

tatgtgttct acatctatgt gggggtggct gacaccctgc tggccatggg cttcttcaga 3060

ggcctgcccc tggtgcacac cctgatcaca gtgagcaaga tcctgcacca caagatgctg 3120

cactctgtgc tgcaggcccc catgagcacc ctgaacaccc tgaaggctgg gggcatcctg 3180

aacagattca gcaaggacat tgccatcctg gatgacctgc tgcccctgac catctttgac 3240

ttcatccagc tgctgctgat tgtgattggg gccattgctg tggtggctgt gctgcagccc 3300

tacatctttg tggccacagt gcctgtgatt gtggccttca tcatgctgag agcctacttc 3360

ctgcagacca gccagcagct gaagcagctg gagtctgagg gcagaagccc catcttcacc 3420

cacctggtga ccagcctgaa gggcctgtgg accctgagag cctttggcag acagccctac 3480

tttgagaccc tgttccacaa ggccctgaac ctgcacacag ccaactggtt cctgtacctg 3540

agcaccctga gatggttcca gatgagaatt gagatgatct ttgtgatctt cttcattgct 3600

gtgaccttca tcagcatcct gaccacaggg gagggggagg gcagagtggg catcatcctg 3660

accctggcca tgaacatcat gagcaccctg cagtgggctg tgaacagcag cattgatgtg 3720

gacagcctga tgagatctgt gagcagagtg ttcaagttca ttgacatgcc cacagagggc 3780

aagcccacca agagcaccaa gccctacaag aatggccagc tgagcaaggt gatgatcatt 3840

gagaacagcc atgtgaagaa ggatgacatc tggccctctg ggggccagat gacagtgaag 3900

gacctgacag ccaagtacac agaggggggc aatgccatcc tggagaacat cagcttcagc 3960

atcagccctg gccagagagt gggcctgctg ggcagaacag gctctggcaa gagcaccctg 4020

ctgtctgcct tcctgagact gctgaacaca gagggggaga tccagattga tggggtgagc 4080

tgggacagca tcaccctgca gcagtggaga aaggcctttg gggtgatccc ccagaaggtg 4140

ttcatcttct ctggcacctt cagaaagaac ctggacccct atgagcagtg gtctgaccag 4200

gagatctgga aggtggctga tgaggtgggc ctgagatctg tgattgagca gttccctggc 4260

aagctggact ttgtgctggt ggatgggggc tgtgtgctga gccatggcca caagcagctg 4320

atgtgcctgg ccagatctgt gctgagcaag gccaagatcc tgctgctgga tgagccctct 4380

gcccacctgg accctgtgac ctaccagatc atcagaagaa ccctgaagca ggcctttgct 4440

gactgcacag tgatcctgtg tgagcacaga attgaggcca tgctggagtg ccagcagttc 4500

ctggtgattg aggagaacaa ggtgagacag tatgacagca tccagaagct gctgaatgag 4560

agaagcctgt tcagacaggc catcagcccc tctgacagag tgaagctgtt cccccacaga 4620

aacagcagca agtgcaagag caagccccag attgctgccc tgaaggagga gaccgaggag 4680

gaggtgcagg acaccagact gtaaataaaa tacgaaatgg atctgaggaa cccctagtga 4740

tggagttggc cactccctct ctgcgcgctc gctcgctcac tgaggccggg cgaccaaagg 4800

tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag cgagcgagcg cgcagagagg 4860

gagtggccaa ttaattaagg cgatgaacgg taatcgtaaa actagcatgt caatcatatg 4920

taccccggtt gataatcaga aaagccccaa aaacaggaag attgtataag cattaattaa 4980

tttaaataca tggacatgtc agaattggtt aattggttgt aacactgacc cctatttgtt 5040

tatttttcta aatacattca aatatgtatc cgctcatgag acaataaccc tgataaatgc 5100

ttcaataata ttgaaaaagg aagaatatga gccatattca acgggaaacg tcgaggccgc 5160

gattaaattc caacatggat gctgatttat atgggtataa atgggctcgc gataatgtcg 5220

ggcaatcagg tgcgacaatc tatcgcttgt atgggaagcc cgatgcgcca gagttgtttc 5280

tgaaacatgg caaaggtagc gttgccaatg atgttacaga tgagatggtc agactaaact 5340

ggctgacgga atttatgcca cttccgacca tcaagcattt tatccgtact cctgatgatg 5400

catggttact caccactgcg atccccggaa aaacagcgtt ccaggtatta gaagaatatc 5460

ctgattcagg tgaaaatatt gttgatgcgc tggcagtgtt cctgcgccgg ttgcactcga 5520

ttcctgtttg taattgtcct tttaacagcg atcgcgtatt tcgcctcgct caggcgcaat 5580

cacgaatgaa taacggtttg gttgatgcga gtgattttga tgacgagcgt aatggctggc 5640

ctgttgaaca agtctggaaa gaaatgcata aacttttgcc attctcaccg gattcagtcg 5700

tcactcatgg tgatttctca cttgataacc ttatttttga cgaggggaaa ttaataggtt 5760

gtattgatgt tggacgagtc ggaatcgcag accgatacca ggatcttgcc atcctatgga 5820

actgcctcgg tgagttttct ccttcattac agaaacggct ttttcaaaaa tatggtattg 5880

ataatcctga tatgaataaa ttgcagtttc atttgatgct cgatgagttt ttctaaaagc 5940

agagcattac gctgacttga cgggacggcg caagctcatg accaaaatcc cttaacgtga 6000

gttacgcgcg cgtcgttcca ctgagcgtca gaccccgtag aaaagatcaa aggatcttct 6060

tgagatcctt tttttctgcg cgtaatctgc tgcttgcaaa caaaaaaacc accgctacca 6120

gcggtggttt gtttgccgga tcaagagcta ccaactcttt ttccgaaggt aactggcttc 6180

agcagagcgc agataccaaa tactgttctt ctagtgtagc cgtagttagc ccaccacttc 6240

aagaactctg tagcaccgcc tacatacctc gctctgctaa tcctgttacc agtggctgct 6300

gccagtggcg ataagtcgtg tcttaccggg ttggactcaa gacgatagtt accggataag 6360

gcgcagcggt cgggctgaac ggggggttcg tgcacacagc ccagcttgga gcgaacgacc 6420

tacaccgaac tgagatacct acagcgtgag ctatgagaaa gcgccacgct tcccgaaggg 6480

agaaaggcgg acaggtatcc ggtaagcggc agggtcggaa caggagagcg cacgagggag 6540

cttccagggg gaaacgcctg gtatctttat agtcctgtcg ggtttcgcca cctctgactt 6600

gagcgtcgat ttttgtgatg ctcgtcaggg gggcggagcc tatggaaaaa cgccagcaac 6660

gcggcctttt tacggttcct ggccttttgc tggccttttg ctcacatgtt taaaccatg 6719

<210> 89

<211> 6751

<212> DNA

<213> 人工序列

<220>

<223> pA-CF3

<400> 89

tcctgcaggc agctgcgcgc tcgctcgctc actgaggccg cccgggcaaa gcccgggcgt 60

cgggcgacct ttggtcgccc ggcctcagtg agcgagcgag cgcgcagaga gggagtggcc 120

aactccatca ctaggggttc ctgcggccgc atggaggcgg tactatgtag atgagaattc 180

aggagcaaac tgggaaaagc aactgcttcc aaatatttgt gatttttaca gtgtagtttt 240

ggaaaaactc ttagcctacc aattcttcta agtgttttaa aatgtgggag ccagtacaca 300

tgaagttata gagtgtttta atgaggctta aatatttacc gtaactatga aatgctacgc 360

atatcatgct gttcaggctc cgtggccacg caactcatac cggtagtact cgccaccatg 420

cagagaagcc ccctggagaa ggcctctgtg gtgagcaagc tgttcttcag ctggaccaga 480

cccatcctga gaaagggcta cagacagaga ctggagctgt ctgacatcta ccagatcccc 540

tctgtggact ctgctgacaa cctgtctgag aagctggaga gagagtggga cagagagctg 600

gccagcaaga agaaccccaa gctgatcaat gccctgagaa gatgcttctt ctggagattc 660

atgttctatg gcatcttcct gtacctgggg gaggtgacca aggctgtgca gcccctgctg 720

ctgggcagaa tcattgccag ctatgaccct gacaacaagg aggagagaag cattgccatc 780

tacctgggca ttggcctgtg cctgctgttc attgtgagaa ccctgctgct gcaccctgcc 840

atctttggcc tgcaccacat tggcatgcag atgagaattg ccatgttcag cctgatctac 900

aagaagaccc tgaagctgag cagcagagtg ctggacaaga tcagcattgg ccagctggtg 960

agcctgctga gcaacaacct gaacaagttt gatgagggcc tggccctggc ccactttgtg 1020

tggattgccc ccctgcaggt ggccctgctg atgggcctga tctgggagct gctgcaggcc 1080

tctgccttct gtggcctggg cttcctgatt gtgctggccc tgttccaggc tggcctgggc 1140

agaatgatga tgaagtacag agaccagaga gctggcaaga tctctgagag actggtgatc 1200

acctctgaga tgattgagaa catccagtct gtgaaggcct actgctggga ggaggccatg 1260

gagaagatga ttgagaacct gagacagaca gagctgaagc tgaccagaaa ggctgcctat 1320

gtgagatact tcaacagctc tgccttcttc ttctctggct tctttgtggt gttcctgtct 1380

gtgctgccct atgccctgat caagggcatc atcctgagaa agatcttcac caccatcagc 1440

ttctgcattg tgctgagaat ggctgtgacc agacagttcc cctgggctgt gcagacctgg 1500

tatgacagcc tgggggccat caacaagatc caggacttcc tgcagaagca ggagtacaag 1560

accctggagt acaacctgac caccacagag gtggtgatgg agaatgtgac agccttctgg 1620

gaggagggct ttggggagct gtttgagaag gccaagcaga acaacaacaa cagaaagacc 1680

agcaatgggg atgacagcct gttcttcagc aacttcagcc tgctgggcac ccctgtgctg 1740

aaggacatca acttcaagat tgagagaggc cagctgctgg ctgtggctgg cagcacaggg 1800

gctggcaaga ccagcctgct gatgatgatc atgggggagc tggagccctc tgagggcaag 1860

atcaagcact ctggcagaat cagcttctgc agccagttca gctggatcat gcctggcacc 1920

atcaaggaga acatcatctt tggggtgagc tatgatgagt acagatacag atctgtgatc 1980

aaggcctgcc agctggagga ggacatcagc aagtttgctg agaaggacaa cattgtgctg 2040

ggggaggggg gcatcaccct gtctgggggc cagagagcca gaatcagcct ggccagagct 2100

gtgtacaagg atgctgacct gtacctgctg gacagcccct ttggctacct ggatgtgctg 2160

acagagaagg agatctttga gagctgtgtg tgcaagctga tggccaacaa gaccagaatc 2220

ctggtgacca gcaagatgga gcacctgaag aaggctgaca agatcctgat cctgcatgag 2280

ggcagcagct acttctatgg caccttctct gagctgcaga acctgcagcc tgacttcagc 2340

agcaagctga tgggctgtga cagctttgac cagttctctg ctgagagaag aaacagcatc 2400

ctgacagaga ccctgcacag attcagcctg gagggggatg cccctgtgag ctggacagag 2460

accaagaagc agagcttcaa gcagacaggg gagtttgggg agaagagaaa gaacagcatc 2520

ctgaacccca tcaacagcac cctgcaggcc agaagaagac agtctgtgct gaacctgatg 2580

acccactctg tgaaccaggg ccagaacatc cacagaaaga ccacagccag caccagaaag 2640

gtgagcctgg ccccccaggc caacctgaca gagctggaca tctacagcag aagactgagc 2700

caggagacag gcctggagat ctctgaggag atcaatgagg aggacctgaa ggagtgcttc 2760

tttgatgaca tggagagcat ccctgctgtg accacctgga acacctacct gagatacatc 2820

acagtgcaca agagcctgat ctttgtgctg atctggtgcc tggtgatctt cctggctgag 2880

gtggctgcca gcctggtggt gctgtggctg ctgggcaaca cccccctgca ggacaagggc 2940

aacagcaccc acagcagaaa caacagctat gctgtgatca tcaccagcac cagcagctac 3000

tatgtgttct acatctatgt gggggtggct gacaccctgc tggccatggg cttcttcaga 3060

ggcctgcccc tggtgcacac cctgatcaca gtgagcaaga tcctgcacca caagatgctg 3120

cactctgtgc tgcaggcccc catgagcacc ctgaacaccc tgaaggctgg gggcatcctg 3180

aacagattca gcaaggacat tgccatcctg gatgacctgc tgcccctgac catctttgac 3240

ttcatccagc tgctgctgat tgtgattggg gccattgctg tggtggctgt gctgcagccc 3300

tacatctttg tggccacagt gcctgtgatt gtggccttca tcatgctgag agcctacttc 3360

ctgcagacca gccagcagct gaagcagctg gagtctgagg gcagaagccc catcttcacc 3420

cacctggtga ccagcctgaa gggcctgtgg accctgagag cctttggcag acagccctac 3480

tttgagaccc tgttccacaa ggccctgaac ctgcacacag ccaactggtt cctgtacctg 3540

agcaccctga gatggttcca gatgagaatt gagatgatct ttgtgatctt cttcattgct 3600

gtgaccttca tcagcatcct gaccacaggg gagggggagg gcagagtggg catcatcctg 3660

accctggcca tgaacatcat gagcaccctg cagtgggctg tgaacagcag cattgatgtg 3720

gacagcctga tgagatctgt gagcagagtg ttcaagttca ttgacatgcc cacagagggc 3780

aagcccacca agagcaccaa gccctacaag aatggccagc tgagcaaggt gatgatcatt 3840

gagaacagcc atgtgaagaa ggatgacatc tggccctctg ggggccagat gacagtgaag 3900

gacctgacag ccaagtacac agaggggggc aatgccatcc tggagaacat cagcttcagc 3960

atcagccctg gccagagagt gggcctgctg ggcagaacag gctctggcaa gagcaccctg 4020

ctgtctgcct tcctgagact gctgaacaca gagggggaga tccagattga tggggtgagc 4080

tgggacagca tcaccctgca gcagtggaga aaggcctttg gggtgatccc ccagaaggtg 4140

ttcatcttct ctggcacctt cagaaagaac ctggacccct atgagcagtg gtctgaccag 4200

gagatctgga aggtggctga tgaggtgggc ctgagatctg tgattgagca gttccctggc 4260

aagctggact ttgtgctggt ggatgggggc tgtgtgctga gccatggcca caagcagctg 4320

atgtgcctgg ccagatctgt gctgagcaag gccaagatcc tgctgctgga tgagccctct 4380

gcccacctgg accctgtgac ctaccagatc atcagaagaa ccctgaagca ggcctttgct 4440

gactgcacag tgatcctgtg tgagcacaga attgaggcca tgctggagtg ccagcagttc 4500

ctggtgattg aggagaacaa ggtgagacag tatgacagca tccagaagct gctgaatgag 4560

agaagcctgt tcagacaggc catcagcccc tctgacagag tgaagctgtt cccccacaga 4620

aacagcagca agtgcaagag caagccccag attgctgccc tgaaggagga gaccgaggag 4680

gaggtgcagg acaccagact gtaaataaat atctttattt tcattacatc tgtgtgttgg 4740

ttttttgtgt ggatctgagg aacccctagt gatggagttg gccactccct ctctgcgcgc 4800

tcgctcgctc actgaggccg ggcgaccaaa ggtcgcccga cgcccgggct ttgcccgggc 4860

ggcctcagtg agcgagcgag cgcgcagaga gggagtggcc aattaattaa ggcgatgaac 4920

ggtaatcgta aaactagcat gtcaatcata tgtaccccgg ttgataatca gaaaagcccc 4980

aaaaacagga agattgtata agcattaatt aatttaaata catggacatg tcagaattgg 5040

ttaattggtt gtaacactga cccctatttg tttatttttc taaatacatt caaatatgta 5100

tccgctcatg agacaataac cctgataaat gcttcaataa tattgaaaaa ggaagaatat 5160

gagccatatt caacgggaaa cgtcgaggcc gcgattaaat tccaacatgg atgctgattt 5220

atatgggtat aaatgggctc gcgataatgt cgggcaatca ggtgcgacaa tctatcgctt 5280

gtatgggaag cccgatgcgc cagagttgtt tctgaaacat ggcaaaggta gcgttgccaa 5340

tgatgttaca gatgagatgg tcagactaaa ctggctgacg gaatttatgc cacttccgac 5400

catcaagcat tttatccgta ctcctgatga tgcatggtta ctcaccactg cgatccccgg 5460

aaaaacagcg ttccaggtat tagaagaata tcctgattca ggtgaaaata ttgttgatgc 5520

gctggcagtg ttcctgcgcc ggttgcactc gattcctgtt tgtaattgtc cttttaacag 5580

cgatcgcgta tttcgcctcg ctcaggcgca atcacgaatg aataacggtt tggttgatgc 5640

gagtgatttt gatgacgagc gtaatggctg gcctgttgaa caagtctgga aagaaatgca 5700

taaacttttg ccattctcac cggattcagt cgtcactcat ggtgatttct cacttgataa 5760

ccttattttt gacgagggga aattaatagg ttgtattgat gttggacgag tcggaatcgc 5820

agaccgatac caggatcttg ccatcctatg gaactgcctc ggtgagtttt ctccttcatt 5880

acagaaacgg ctttttcaaa aatatggtat tgataatcct gatatgaata aattgcagtt 5940

tcatttgatg ctcgatgagt ttttctaaaa gcagagcatt acgctgactt gacgggacgg 6000

cgcaagctca tgaccaaaat cccttaacgt gagttacgcg cgcgtcgttc cactgagcgt 6060

cagaccccgt agaaaagatc aaaggatctt cttgagatcc tttttttctg cgcgtaatct 6120

gctgcttgca aacaaaaaaa ccaccgctac cagcggtggt ttgtttgccg gatcaagagc 6180

taccaactct ttttccgaag gtaactggct tcagcagagc gcagatacca aatactgttc 6240

ttctagtgta gccgtagtta gcccaccact tcaagaactc tgtagcaccg cctacatacc 6300

tcgctctgct aatcctgtta ccagtggctg ctgccagtgg cgataagtcg tgtcttaccg 6360

ggttggactc aagacgatag ttaccggata aggcgcagcg gtcgggctga acggggggtt 6420

cgtgcacaca gcccagcttg gagcgaacga cctacaccga actgagatac ctacagcgtg 6480

agctatgaga aagcgccacg cttcccgaag ggagaaaggc ggacaggtat ccggtaagcg 6540

gcagggtcgg aacaggagag cgcacgaggg agcttccagg gggaaacgcc tggtatcttt 6600

atagtcctgt cgggtttcgc cacctctgac ttgagcgtcg atttttgtga tgctcgtcag 6660

gggggcggag cctatggaaa aacgccagca acgcggcctt tttacggttc ctggcctttt 6720

gctggccttt tgctcacatg tttaaaccat g 6751

<210> 90

<211> 6603

<212> DNA

<213> 人工序列

<220>

<223> pA-CF5

<400> 90

tcctgcaggc agctgcgcgc tcgctcgctc actgaggccg cccgggcaaa gcccgggcgt 60

cgggcgacct ttggtcgccc ggcctcagtg agcgagcgag cgcgcagaga gggagtggcc 120

aactccatca ctaggggttc ctgcggccgc aatatttgca tgtcgctatg tgttctggga 180

aatcaccata aacgtgaaat gtctttggat ttgggaatct tcgaagttct gtatgagacc 240

acagatctcc accggtagta ctcgccacca tgcagagaag ccccctggag aaggcctctg 300

tggtgagcaa gctgttcttc agctggacca gacccatcct gagaaagggc tacagacaga 360

gactggagct gtctgacatc taccagatcc cctctgtgga ctctgctgac aacctgtctg 420

agaagctgga gagagagtgg gacagagagc tggccagcaa gaagaacccc aagctgatca 480

atgccctgag aagatgcttc ttctggagat tcatgttcta tggcatcttc ctgtacctgg 540

gggaggtgac caaggctgtg cagcccctgc tgctgggcag aatcattgcc agctatgacc 600

ctgacaacaa ggaggagaga agcattgcca tctacctggg cattggcctg tgcctgctgt 660

tcattgtgag aaccctgctg ctgcaccctg ccatctttgg cctgcaccac attggcatgc 720

agatgagaat tgccatgttc agcctgatct acaagaagac cctgaagctg agcagcagag 780

tgctggacaa gatcagcatt ggccagctgg tgagcctgct gagcaacaac ctgaacaagt 840

ttgatgaggg cctggccctg gcccactttg tgtggattgc ccccctgcag gtggccctgc 900

tgatgggcct gatctgggag ctgctgcagg cctctgcctt ctgtggcctg ggcttcctga 960

ttgtgctggc cctgttccag gctggcctgg gcagaatgat gatgaagtac agagaccaga 1020

gagctggcaa gatctctgag agactggtga tcacctctga gatgattgag aacatccagt 1080

ctgtgaaggc ctactgctgg gaggaggcca tggagaagat gattgagaac ctgagacaga 1140

cagagctgaa gctgaccaga aaggctgcct atgtgagata cttcaacagc tctgccttct 1200

tcttctctgg cttctttgtg gtgttcctgt ctgtgctgcc ctatgccctg atcaagggca 1260

tcatcctgag aaagatcttc accaccatca gcttctgcat tgtgctgaga atggctgtga 1320

ccagacagtt cccctgggct gtgcagacct ggtatgacag cctgggggcc atcaacaaga 1380

tccaggactt cctgcagaag caggagtaca agaccctgga gtacaacctg accaccacag 1440

aggtggtgat ggagaatgtg acagccttct gggaggaggg ctttggggag ctgtttgaga 1500

aggccaagca gaacaacaac aacagaaaga ccagcaatgg ggatgacagc ctgttcttca 1560

gcaacttcag cctgctgggc acccctgtgc tgaaggacat caacttcaag attgagagag 1620

gccagctgct ggctgtggct ggcagcacag gggctggcaa gaccagcctg ctgatgatga 1680

tcatggggga gctggagccc tctgagggca agatcaagca ctctggcaga atcagcttct 1740

gcagccagtt cagctggatc atgcctggca ccatcaagga gaacatcatc tttggggtga 1800

gctatgatga gtacagatac agatctgtga tcaaggcctg ccagctggag gaggacatca 1860

gcaagtttgc tgagaaggac aacattgtgc tgggggaggg gggcatcacc ctgtctgggg 1920

gccagagagc cagaatcagc ctggccagag ctgtgtacaa ggatgctgac ctgtacctgc 1980

tggacagccc ctttggctac ctggatgtgc tgacagagaa ggagatcttt gagagctgtg 2040

tgtgcaagct gatggccaac aagaccagaa tcctggtgac cagcaagatg gagcacctga 2100

agaaggctga caagatcctg atcctgcatg agggcagcag ctacttctat ggcaccttct 2160

ctgagctgca gaacctgcag cctgacttca gcagcaagct gatgggctgt gacagctttg 2220

accagttctc tgctgagaga agaaacagca tcctgacaga gaccctgcac agattcagcc 2280

tggaggggga tgcccctgtg agctggacag agaccaagaa gcagagcttc aagcagacag 2340

gggagtttgg ggagaagaga aagaacagca tcctgaaccc catcaacagc accctgcagg 2400

ccagaagaag acagtctgtg ctgaacctga tgacccactc tgtgaaccag ggccagaaca 2460

tccacagaaa gaccacagcc agcaccagaa aggtgagcct ggccccccag gccaacctga 2520

cagagctgga catctacagc agaagactga gccaggagac aggcctggag atctctgagg 2580

agatcaatga ggaggacctg aaggagtgct tctttgatga catggagagc atccctgctg 2640

tgaccacctg gaacacctac ctgagataca tcacagtgca caagagcctg atctttgtgc 2700

tgatctggtg cctggtgatc ttcctggctg aggtggctgc cagcctggtg gtgctgtggc 2760

tgctgggcaa cacccccctg caggacaagg gcaacagcac ccacagcaga aacaacagct 2820

atgctgtgat catcaccagc accagcagct actatgtgtt ctacatctat gtgggggtgg 2880

ctgacaccct gctggccatg ggcttcttca gaggcctgcc cctggtgcac accctgatca 2940

cagtgagcaa gatcctgcac cacaagatgc tgcactctgt gctgcaggcc cccatgagca 3000

ccctgaacac cctgaaggct gggggcatcc tgaacagatt cagcaaggac attgccatcc 3060

tggatgacct gctgcccctg accatctttg acttcatcca gctgctgctg attgtgattg 3120

gggccattgc tgtggtggct gtgctgcagc cctacatctt tgtggccaca gtgcctgtga 3180

ttgtggcctt catcatgctg agagcctact tcctgcagac cagccagcag ctgaagcagc 3240

tggagtctga gggcagaagc cccatcttca cccacctggt gaccagcctg aagggcctgt 3300

ggaccctgag agcctttggc agacagccct actttgagac cctgttccac aaggccctga 3360

acctgcacac agccaactgg ttcctgtacc tgagcaccct gagatggttc cagatgagaa 3420

ttgagatgat ctttgtgatc ttcttcattg ctgtgacctt catcagcatc ctgaccacag 3480

gggaggggga gggcagagtg ggcatcatcc tgaccctggc catgaacatc atgagcaccc 3540

tgcagtgggc tgtgaacagc agcattgatg tggacagcct gatgagatct gtgagcagag 3600

tgttcaagtt cattgacatg cccacagagg gcaagcccac caagagcacc aagccctaca 3660

agaatggcca gctgagcaag gtgatgatca ttgagaacag ccatgtgaag aaggatgaca 3720

tctggccctc tgggggccag atgacagtga aggacctgac agccaagtac acagaggggg 3780

gcaatgccat cctggagaac atcagcttca gcatcagccc tggccagaga gtgggcctgc 3840

tgggcagaac aggctctggc aagagcaccc tgctgtctgc cttcctgaga ctgctgaaca 3900

cagaggggga gatccagatt gatggggtga gctgggacag catcaccctg cagcagtgga 3960

gaaaggcctt tggggtgatc ccccagaagg tgttcatctt ctctggcacc ttcagaaaga 4020

acctggaccc ctatgagcag tggtctgacc aggagatctg gaaggtggct gatgaggtgg 4080

gcctgagatc tgtgattgag cagttccctg gcaagctgga ctttgtgctg gtggatgggg 4140

gctgtgtgct gagccatggc cacaagcagc tgatgtgcct ggccagatct gtgctgagca 4200

aggccaagat cctgctgctg gatgagccct ctgcccacct ggaccctgtg acctaccaga 4260

tcatcagaag aaccctgaag caggcctttg ctgactgcac agtgatcctg tgtgagcaca 4320

gaattgaggc catgctggag tgccagcagt tcctggtgat tgaggagaac aaggtgagac 4380

agtatgacag catccagaag ctgctgaatg agagaagcct gttcagacag gccatcagcc 4440

cctctgacag agtgaagctg ttcccccaca gaaacagcag caagtgcaag agcaagcccc 4500

agattgctgc cctgaaggag gagaccgagg aggaggtgca ggacaccaga ctgtaaataa 4560

atatctttat tttcattaca tctgtgtgtt ggttttttgt gtggatctga ggaaccccta 4620

gtgatggagt tggccactcc ctctctgcgc gctcgctcgc tcactgaggc cgggcgacca 4680

aaggtcgccc gacgcccggg ctttgcccgg gcggcctcag tgagcgagcg agcgcgcaga 4740

gagggagtgg ccaattaatt aaggcgatga acggtaatcg taaaactagc atgtcaatca 4800

tatgtacccc ggttgataat cagaaaagcc ccaaaaacag gaagattgta taagcattaa 4860

ttaatttaaa tacatggaca tgtcagaatt ggttaattgg ttgtaacact gacccctatt 4920

tgtttatttt tctaaataca ttcaaatatg tatccgctca tgagacaata accctgataa 4980

atgcttcaat aatattgaaa aaggaagaat atgagccata ttcaacggga aacgtcgagg 5040

ccgcgattaa attccaacat ggatgctgat ttatatgggt ataaatgggc tcgcgataat 5100

gtcgggcaat caggtgcgac aatctatcgc ttgtatggga agcccgatgc gccagagttg 5160

tttctgaaac atggcaaagg tagcgttgcc aatgatgtta cagatgagat ggtcagacta 5220

aactggctga cggaatttat gccacttccg accatcaagc attttatccg tactcctgat 5280

gatgcatggt tactcaccac tgcgatcccc ggaaaaacag cgttccaggt attagaagaa 5340

tatcctgatt caggtgaaaa tattgttgat gcgctggcag tgttcctgcg ccggttgcac 5400

tcgattcctg tttgtaattg tccttttaac agcgatcgcg tatttcgcct cgctcaggcg 5460

caatcacgaa tgaataacgg tttggttgat gcgagtgatt ttgatgacga gcgtaatggc 5520

tggcctgttg aacaagtctg gaaagaaatg cataaacttt tgccattctc accggattca 5580

gtcgtcactc atggtgattt ctcacttgat aaccttattt ttgacgaggg gaaattaata 5640

ggttgtattg atgttggacg agtcggaatc gcagaccgat accaggatct tgccatccta 5700

tggaactgcc tcggtgagtt ttctccttca ttacagaaac ggctttttca aaaatatggt 5760

attgataatc ctgatatgaa taaattgcag tttcatttga tgctcgatga gtttttctaa 5820

aagcagagca ttacgctgac ttgacgggac ggcgcaagct catgaccaaa atcccttaac 5880

gtgagttacg cgcgcgtcgt tccactgagc gtcagacccc gtagaaaaga tcaaaggatc 5940

ttcttgagat cctttttttc tgcgcgtaat ctgctgcttg caaacaaaaa aaccaccgct 6000

accagcggtg gtttgtttgc cggatcaaga gctaccaact ctttttccga aggtaactgg 6060

cttcagcaga gcgcagatac caaatactgt tcttctagtg tagccgtagt tagcccacca 6120

cttcaagaac tctgtagcac cgcctacata cctcgctctg ctaatcctgt taccagtggc 6180

tgctgccagt ggcgataagt cgtgtcttac cgggttggac tcaagacgat agttaccgga 6240

taaggcgcag cggtcgggct gaacgggggg ttcgtgcaca cagcccagct tggagcgaac 6300

gacctacacc gaactgagat acctacagcg tgagctatga gaaagcgcca cgcttcccga 6360

agggagaaag gcggacaggt atccggtaag cggcagggtc ggaacaggag agcgcacgag 6420

ggagcttcca gggggaaacg cctggtatct ttatagtcct gtcgggtttc gccacctctg 6480

acttgagcgt cgatttttgt gatgctcgtc aggggggcgg agcctatgga aaaacgccag 6540

caacgcggcc tttttacggt tcctggcctt ttgctggcct tttgctcaca tgtttaaacc 6600

atg 6603

<210> 91

<211> 7519

<212> DNA

<213> 人工序列

<220>

<223> pA-CF7

<400> 91

tcctgcaggc agctgcgcgc tcgctcgctc actgaggccg cccgggcaaa gcccgggcgt 60

cgggcgacct ttggtcgccc ggcctcagtg agcgagcgag cgcgcagaga gggagtggcc 120

aactccatca ctaggggttc ctgcggccgc aatatttgca tgtcgctatg tgttctggga 180

aatcaccata aacgtgaaat gtctttggat ttgggaatct tcgaagttct gtatgagacc 240

acagatctcc accggtagta ctcgccacca tgcagagaag ccccctggag aaggcctctg 300

tggtgagcaa gctgttcttc ccccctggag aaggcctctg tggtgagcaa gctgttcttc 360

agctggacca gacccatcct gagaaagggc tacagacaga gactggagct gtctgacatc 420

taccagatcc cctctgtgga ctctgctgac aacctgtctg agaagctgga gagagagtgg 480

gacagagagc tggccagcaa gaagaacccc aagctgatca atgccctgag aagatgcttc 540

ttctggagat tcatgttcta tggcatcttc ctgtacctgg gggaggtgac caaggctgtg 600

cagcccctgc tgctgggcag aatcattgcc agctatgacc cagcccctgc tgctgggcag 660

aatcattgcc agctatgacc ctgacaacaa ggaggagaga agcattgcca tctacctggg 720

cattggcctg tgcctgctgt tcattgtgag aaccctgctg ctgcaccctg ccatctttgg 780

cctgcaccac attggcatgc agatgagaat tgccatgttc agcctgatct acaagaagac 840

cctgaagctg agcagcagag tgctggacaa gatcagcatt ggccagctgg tgagcctgct 900

gagcaacaac ctgaacaagt ttgatgaggg cctggccctg gcccactttg tgtggattgc 960

ttgatgaggg cctggccctg gcccactttg tgtggattgc ccccctgcag gtggccctgc 1020

tgatgggcct gatctgggag ctgctgcagg cctctgcctt ctgtggcctg ggcttcctga 1080

ttgtgctggc cctgttccag gctggcctgg gcagaatgat gatgaagtac agagaccaga 1140

gagctggcaa gatctctgag agactggtga tcacctctga gatgattgag aacatccagt 1200

ctgtgaaggc ctactgctgg gaggaggcca tggagaagat gattgagaac ctgagacaga 1260

cagagctgaa gctgaccaga aaggctgcct atgtgagata cttcaacagc tctgccttct 1320

tcttctctgg cttctttgtg gtgttcctgt ctgtgctgcc tctgccttct tcttctctgg 1380

cttctttgtg gtgttcctgt ctgtgctgcc ctatgccctg atcaagggca tcatcctgag 1440

aaagatcttc accaccatca gcttctgcat tgtgctgaga atggctgtga ccagacagtt 1500

cccctgggct gtgcagacct ggtatgacag cctgggggcc atcaacaaga tccaggactt 1560

cctgcagaag caggagtaca agaccctgga gtacaacctg accaccacag aggtggtgat 1620

ggagaatgtg acagccttct gggaggaggg ctttggggag ctgtttgaga aggccaagca 1680

gaacaacaac aacagaaaga ccagcaatgg ggatgacagc ctgttcttca gcaacttcag 1740

cctgctgggc acccctgtgc ggatgacagc ctgttcttca gcaacttcag cctgctgggc 1800

acccctgtgc tgaaggacat caacttcaag attgagagag gccagctgct ggctgtggct 1860

ggcagcacag gggctggcaa gaccagcctg ctgatgatga tcatggggga gctggagccc 1920

tctgagggca agatcaagca ctctggcaga atcagcttct gcagccagtt cagctggatc 1980

atgcctggca ccatcaagga gaacatcatc tttggggtga gctatgatga gtacagatac 2040

agatctgtga tcaaggcctg ccagctggag gaggacatca agatctgtga tcaaggcctg 2100

ccagctggag gaggacatca gcaagtttgc tgagaaggac aacattgtgc tgggggaggg 2160

gggcatcacc ctgtctgggg gccagagagc cagaatcagc ctggccagag ctgtgtacaa 2220

ggatgctgac ctgtacctgc tggacagccc ctttggctac ctggatgtgc tgacagagaa 2280

ggagatcttt gagagctgtg tgtgcaagct gatggccaac aagaccagaa tcctggtgac 2340

cagcaagatg gagcacctga agaaggctga caagatcctg atcctgcatg agggcagcag 2400

agaaggctga caagatcctg atcctgcatg agggcagcag ctacttctat ggcaccttct 2460

ctgagctgca gaacctgcag cctgacttca gcagcaagct gatgggctgt gacagctttg 2520

accagttctc tgctgagaga agaaacagca tcctgacaga gaccctgcac agattcagcc 2580

tggaggggga tgcccctgtg agctggacag agaccaagaa gcagagcttc aagcagacag 2640

gggagtttgg ggagaagaga aagaacagca tcctgaaccc catcaacagc atcagaaagt 2700

tcagcattgt gcagaagacc catcaacagc atcagaaagt tcagcattgt gcagaagacc 2760

cccctgcaga tgaatggcat tgaggaggac tctgatgagc ccctggagag aagactgagc 2820

ctggtgcctg actctgagca gggggaggcc atcctgccca gaatctctgt gatcagcaca 2880

ggccccaccc tgcaggccag aagaagacag tctgtgctga acctgatgac ccactctgtg 2940

aaccagggcc agaacatcca ccactctgtg aaccagggcc agaacatcca cagaaagacc 3000

acagccagca ccagaaaggt gagcctggcc ccccaggcca acctgacaga gctggacatc 3060

tacagcagaa gactgagcca ggagacaggc ctggagatct ctgaggagat caatgaggag 3120

gacctgaagg agtgcttctt tgatgacatg gagagcatcc ctgctgtgac cacctggaac 3180

acctacctga gatacatcac agtgcacaag agcctgatct ttgtgctgat ctggtgcctg 3240

gtgatcttcc tggctgaggt ggctgccagc ctggtggtgc gtgatcttcc tggctgaggt 3300

ggctgccagc ctggtggtgc tgtggctgct gggcaacacc cccctgcagg acaagggcaa 3360

cagcacccac agcagaaaca acagctatgc tgtgatcatc accagcacca gcagctacta 3420

tgtgttctac atctatgtgg gggtggctga caccctgctg gccatgggct tcttcagagg 3480

cctgcccctg gtgcacaccc tgatcacagt gagcaagatc ctgcaccaca agatgctgca 3540

ctctgtgctg caggccccca tgagcaccct gaacaccctg aaggctgggg gcatcctgaa 3600

tgagcaccct gaacaccctg aaggctgggg gcatcctgaa cagattcagc aaggacattg 3660

ccatcctgga tgacctgctg cccctgacca tctttgactt catccagctg ctgctgattg 3720

tgattggggc cattgctgtg gtggctgtgc tgcagcccta catctttgtg gccacagtgc 3780

ctgtgattgt ggccttcatc atgctgagag cctacttcct gcagaccagc cagcagctga 3840

agcagctgga gtctgagggc agaagcccca tcttcaccca cctggtgacc agcctgaagg 3900

gcctgtggac cctgagagcc cctggtgacc agcctgaagg gcctgtggac cctgagagcc 3960

tttggcagac agccctactt tgagaccctg ttccacaagg ccctgaacct gcacacagcc 4020

aactggttcc tgtacctgag caccctgaga tggttccaga tgagaattga gatgatcttt 4080

gtgatcttct tcattgctgt gaccttcatc agcatcctga ccacagggga gggggagggc 4140

agagtgggca tcatcctgac cctggccatg aacatcatga gcaccctgca gtgggctgtg 4200

aacagcagca ttgatgtgga cagcctgatg agatctgtga gcagagtgtt caagttcatt 4260

gacatgccca cagagggcaa gcccaccaag agcaccaagc cctacaagaa tggccagctg 4320

cagagggcaa gcccaccaag agcaccaagc cctacaagaa tggccagctg agcaaggtga 4380

tgatcattga gaacagccat gtgaagaagg atgacatctg gccctctggg ggccagatga 4440

cagtgaagga cctgacagcc aagtacacag aggggggcaa tgccatcctg gagaacatca 4500

gcttcagcat cagccctggc cagagagtgg gcctgctggg cagaacaggc tctggcaaga 4560

gcaccctgct gtctgccttc ctgagactgc tgaacacaga gggggagatc cagattgatg 4620

gggtgagctg ggacagcatc accctgcagc agtggagaaa ggcctttggg gtgatccccc 4680

agaaggtgtt catcttctct ggcaccttca gaaagaacct gtgatccccc agaaggtgtt 4740

catcttctct ggcaccttca gaaagaacct ggacccctat gagcagtggt ctgaccagga 4800

gatctggaag gtggctgatg aggtgggcct gagatctgtg attgagcagt tccctggcaa 4860

gctggacttt gtgctggtgg atgggggctg tgtgctgagc catggccaca agcagctgat 4920

gtgcctggcc agatctgtgc tgagcaaggc caagatcctg ctgctggatg agccctctgc 4980

ccacctggac cctgtgacct accagatcat cagaagaacc ctgaagcagg cctttgctga 5040

accagatcat cagaagaacc ctgaagcagg cctttgctga ctgcacagtg atcctgtgtg 5100

agcacagaat tgaggccatg ctggagtgcc agcagttcct ggtgattgag gagaacaagg 5160

tgagacagta tgacagcatc cagaagctgc tgaatgagag aagcctgttc agacaggcca 5220

tcagcccctc tgacagagtg aagctgttcc cccacagaaa cagcagcaag tgcaagagca 5280

agccccagat tgctgccctg aaggaggaga ccgaggagga ggtgcaggac accagactgt 5340

aaataaatat ctttattttc attacatctg tgtgttggtt ttttgtgtgg atctgaggaa 5400

cccctagtga tggagttggc cactccctct ctgcgcgctc atctgaggaa cccctagtga 5460

tggagttggc cactccctct ctgcgcgctc gctcgctcac tgaggccggg cgaccaaagg 5520

tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag cgagcgagcg cgcagagagg 5580

gagtggccaa ttaattaagg cgatgaacgg taatcgtaaa actagcatgt caatcatatg 5640

taccccggtt gataatcaga aaagccccaa aaacaggaag attgtataag cattaattaa 5700

tttaaataca tggacatgtc agaattggtt aattggttgt aacactgacc cctatttgtt 5760

tatttttcta aatacattca aatatgtatc cgctcatgag acaataaccc tgataaatgc 5820

ttcaataata ttgaaaaagg aagaatatga gccatattca acgggaaacg tcgaggccgc 5880

gattaaattc caacatggat gctgatttat atgggtataa atgggctcgc gataatgtcg 5940

ggcaatcagg tgcgacaatc tatcgcttgt atgggaagcc cgatgcgcca gagttgtttc 6000

gataatgtcg ggcaatcagg tgcgacaatc tatcgcttgt atgggaagcc cgatgcgcca 6060

gagttgtttc tgaaacatgg caaaggtagc gttgccaatg atgttacaga tgagatggtc 6120

agactaaact ggctgacgga atttatgcca cttccgacca tcaagcattt tatccgtact 6180

cctgatgatg catggttact caccactgcg atccccggaa aaacagcgtt ccaggtatta 6240

gaagaatatc ctgattcagg tgaaaatatt gttgatgcgc tggcagtgtt cctgcgccgg 6300

ttgcactcga ttcctgtttg taattgtcct tttaacagcg atcgcgtatt tcgcctcgct 6360

caggcgcaat cacgaatgaa taacggtttg gttgatgcga gtgattttga tgacgagcgt 6420

aatggctggc ctgttgaaca agtctggaaa gaaatgcata aacttttgcc attctcaccg 6480

gattcagtcg tcactcatgg tgatttctca cttgataacc ttatttttga cgaggggaaa 6540

ttaataggtt gtattgatgt tggacgagtc ggaatcgcag accgatacca ggatcttgcc 6600

atcctatgga actgcctcgg tgagttttct ccttcattac agaaacggct ttttcaaaaa 6660

tatggtattg ataatcctga tatgaataaa ttgcagtttc atttgatgct cgatgagttt 6720

ttctaaaagc agagcattac gctgacttga cgggacggcg caagctcatg accaaaatcc 6780

cttaacgtga gttacgcgcg cgtcgttcca ctgagcgtca gaccccgtag aaaagatcaa 6840

aggatcttct tgagatcctt tttttctgcg cgtaatctgc tgcttgcaaa caaaaaaacc 6900

accgctacca gcggtggttt gtttgccgga tcaagagcta ccaactcttt ttccgaaggt 6960

aactggcttc agcagagcgc agataccaaa tactgttctt ctagtgtagc cgtagttagc 7020

ccaccacttc aagaactctg tagcaccgcc tacatacctc gctctgctaa tcctgttacc 7080

agtggctgct gccagtggcg ataagtcgtg tcttaccggg ttggactcaa gacgatagtt 7140

accggataag gcgcagcggt cgggctgaac ggggggttcg tgcacacagc ccagcttgga 7200

ccagcttgga gcgaacgacc tacaccgaac tgagatacct acagcgtgag ctatgagaaa 7260

gcgccacgct tcccgaaggg agaaaggcgg acaggtatcc ggtaagcggc agggtcggaa 7320

caggagagcg cacgagggag cttccagggg gaaacgcctg gtatctttat agtcctgtcg 7380

ggtttcgcca cctctgactt gagcgtcgat ttttgtgatg ctcgtcaggg gggcggagcc 7440

tatggaaaaa cgccagcaac gcggcctttt tacggttcct ggccttttgc tggccttttg 7500

ctcacatgtt taaaccatg 7519

<210> 92

<211> 11577

<212> DNA

<213> 人工序列

<220>

<223> pHELPK质粒 DNA

<400> 92

ggtacccaac tccatgctta acagtcccca ggtacagccc accctgcgtc gcaaccagga 60

acagctctac agcttcctgg agcgccactc gccctacttc cgcagccaca gtgcgcagat 120

taggagcgcc acttcttttt gtcacttgaa aaacatgtaa aaataatgta ctaggagaca 180

ctttcaataa aggcaaatgt ttttatttgt acactctcgg gtgattattt accccccacc 240

cttgccgtct gcgccgttta aaaatcaaag gggttctgcc gcgcatcgct atgcgccact 300

ggcagggaca cgttgcgata ctggtgttta gtgctccact taaactcagg cacaaccatc 360

cgcggcagct cggtgaagtt ttcactccac aggctgcgca ccatcaccaa cgcgtttagc 420

aggtcgggcg ccgatatctt gaagtcgcag ttggggcctc cgccctgcgc gcgcgagttg 480

cgatacacag ggttgcagca ctggaacact atcagcgccg ggtggtgcac gctggccagc 540

acgctcttgt cggagatcag atccgcgtcc aggtcctccg cgttgctcag ggcgaacgga 600

gtcaactttg gtagctgcct tcccaaaaag ggtgcatgcc caggctttga gttgcactcg 660

caccgtagtg gcatcagaag gtgaccgtgc ccggtctggg cgttaggata cagcgcctgc 720

atgaaagcct tgatctgctt aaaagccacc tgagcctttg cgccttcaga gaagaacatg 780

ccgcaagact tgccggaaaa ctgattggcc ggacaggccg cgtcatgcac gcagcacctt 840

gcgtcggtgt tggagatctg caccacattt cggccccacc ggttcttcac gatcttggcc 900

ttgctagact gctccttcag cgcgcgctgc ccgttttcgc tcgtcacatc catttcaatc 960

acgtgctcct tatttatcat aatgctcccg tgtagacact taagctcgcc ttcgatctca 1020

gcgcagcggt gcagccacaa cgcgcagccc gtgggctcgt ggtgcttgta ggttacctct 1080

gcaaacgact gcaggtacgc ctgcaggaat cgccccatca tcgtcacaaa ggtcttgttg 1140

ctggtgaagg tcagctgcaa cccgcggtgc tcctcgttta gccaggtctt gcatacggcc 1200

gccagagctt ccacttggtc aggcagtagc ttgaagtttg cctttagatc gttatccacg 1260

tggtacttgt ccatcaacgc gcgcgcagcc tccatgccct tctcccacgc agacacgatc 1320

ggcaggctca gcgggtttat caccgtgctt tcactttccg cttcactgga ctcttccttt 1380

tcctcttgcg tccgcatacc ccgcgccact gggtcgtctt cattcagccg ccgcaccgtg 1440

cgcttacctc ccttgccgtg cttgattagc accggtgggt tgctgaaacc caccatttgt 1500

agcgccacat cttctctttc ttcctcgctg tccacgatca cctctgggga tggcgggcgc 1560

tcgggcttgg gagaggggcg cttctttttc tttttggacg caatggccaa atccgccgtc 1620

gaggtcgatg gccgcgggct gggtgtgcgc ggcaccagcg catcttgtga cgagtcttct 1680

tcgtcctcgg actcgagacg ccgcctcagc cgcttttttg ggggcgcgcg gggaggcggc 1740

ggcgacggcg acggggacga cacgtcctcc atggttggtg gacgtcgcgc cgcaccgcgt 1800

ccgcgctcgg gggtggtttc gcgctgctcc tcttcccgac tggccatttc cttctcctat 1860

aggcagaaaa agatcatgga gtcagtcgag aaggaggaca gcctaaccgc cccctttgag 1920

ttcgccacca ccgcctccac cgatgccgcc aacgcgccta ccaccttccc cgtcgaggca 1980

cccccgcttg aggaggagga agtgattatc gagcaggacc caggttttgt aagcgaagac 2040

gacgaggatc gctcagtacc aacagaggat aaaaagcaag accaggacga cgcagaggca 2100

aacgaggaac aagtcgggcg gggggaccaa aggcatggcg actacctaga tgtgggagac 2160

gacgtgctgt tgaagcatct gcagcgccag tgcgccatta tctgcgacgc gttgcaagag 2220

cgcagcgatg tgcccctcgc catagcggat gtcagccttg cctacgaacg ccacctgttc 2280

tcaccgcgcg taccccccaa acgccaagaa aacggcacat gcgagcccaa cccgcgcctc 2340

aacttctacc ccgtatttgc cgtgccagag gtgcttgcca cctatcacat ctttttccaa 2400

aactgcaaga tacccctatc ctgccgtgcc aaccgcagcc gagcggacaa gcagctggcc 2460

ttgcggcagg gcgctgtcat acctgatatc gcctcgctcg acgaagtgcc aaaaatcttt 2520

gagggtcttg gacgcgacga gaaacgcgcg gcaaacgctc tgcaacaaga aaacagcgaa 2580

aatgaaagtc actgtggagt gctggtggaa cttgagggtg acaacgcgcg cctagccgtg 2640

ctgaaacgca gcatcgaggt cacccacttt gcctacccgg cacttaacct accccccaag 2700

gttatgagca cagtcatgag cgagctgatc gtgcgccgtg cacgacccct ggagagggat 2760

gcaaacttgc aagaacaaac cgaggagggc ctacccgcag ttggcgatga gcagctggcg 2820

cgctggcttg agacgcgcga gcctgccgac ttggaggagc gacgcaagct aatgatggcc 2880

gcagtgcttg ttaccgtgga gcttgagtgc atgcagcggt tctttgctga cccggagatg 2940

cagcgcaagc tagaggaaac gttgcactac acctttcgcc agggctacgt gcgccaggcc 3000

tgcaaaattt ccaacgtgga gctctgcaac ctggtctcct accttggaat tttgcacgaa 3060

aaccgcctcg ggcaaaacgt gcttcattcc acgctcaagg gcgaggcgcg ccgcgactac 3120

gtccgcgact gcgtttactt atttctgtgc tacacctggc aaacggccat gggcgtgtgg 3180

cagcaatgcc tggaggagcg caacctaaag gagctgcaga agctgctaaa gcaaaacttg 3240

aaggacctat ggacggcctt caacgagcgc tccgtggccg cgcacctggc ggacattatc 3300

ttccccgaac gcctgcttaa aaccctgcaa cagggtctgc cagacttcac cagtcaaagc 3360

atgttgcaaa actttaggaa ctttatccta gagcgttcag gaattctgcc cgccacctgc 3420

tgtgcgcttc ctagcgactt tgtgcccatt aagtaccgtg aatgccctcc gccgctttgg 3480

ggtcactgct accttctgca gctagccaac taccttgcct accactccga catcatggaa 3540

gacgtgagcg gtgacggcct actggagtgt cactgtcgct gcaacctatg caccccgcac 3600

cgctccctgg tctgcaattc gcaactgctt agcgaaagtc aaattatcgg tacctttgag 3660

ctgcagggtc cctcgcctga cgaaaagtcc gcggctccgg ggttgaaact cactccgggg 3720

ctgtggacgt cggcttacct tcgcaaattt gtacctgagg actaccacgc ccacgagatt 3780

aggttctacg aagaccaatc ccgcccgcca aatgcggagc ttaccgcctg cgtcattacc 3840

cagggccaca tccttggcca attgcaagcc atcaacaaag cccgccaaga gtttctgcta 3900

cgaaagggac ggggggttta cctggacccc cagtccggcg aggagctcaa cccaatcccc 3960

ccgccgccgc agccctatca gcagccgcgg gcccttgctt cccaggatgg cacccaaaaa 4020

gaagctgcag ctgccgccgc cgccacccac ggacgaggag gaatactggg acagtcaggc 4080

agaggaggtt ttggacgagg aggaggagat gatggaagac tgggacagcc tagacgaagc 4140

ttccgaggcc gaagaggtgt cagacgaaac accgtcaccc tcggtcgcat tcccctcgcc 4200

ggcgccccag aaattggcaa ccgttcccag catcgctaca acctccgctc ctcaggcgcc 4260

gccggcactg cctgttcgcc gacccaaccg tagatgggac accactggaa ccagggccgg 4320

taagtctaag cagccgccgc cgttagccca agagcaacaa cagcgccaag gctaccgctc 4380

gtggcgcggg cacaagaacg ccatagttgc ttgcttgcaa gactgtgggg gcaacatctc 4440

cttcgcccgc cgctttcttc tctaccatca cggcgtggcc ttcccccgta acatcctgca 4500

ttactaccgt catctctaca gcccctactg caccggcggc agcggcagcg gcagcaacag 4560

cagcggtcac acagaagcaa aggcgaccgg atagcaagac tctgacaaag cccaagaaat 4620

ccacagcggc ggcagcagca ggaggaggag cgctgcgtct ggcgcccaac gaacccgtat 4680

cgacccgcga gcttagaaat aggatttttc ccactctgta tgctatattt caacaaagca 4740

ggggccaaga acaagagctg aaaataaaaa acaggtctct gcgctccctc acccgcagct 4800

gcctgtatca caaaagcgaa gatcagcttc ggcgcacgct ggaagacgcg gaggctctct 4860

tcagcaaata ctgcgcgctg actcttaagg actagtttcg cgccctttct caaatttaag 4920

cgcgaaaact acgtcatctc cagcggccac acccggcgcc agcacctgtc gtcagcgcca 4980

ttatgagcaa ggaaattccc acgccctaca tgtggagtta ccagccacaa atgggacttg 5040

cggctggagc tgcccaagac tactcaaccc gaataaacta catgagcgcg ggaccccaca 5100

tgatatcccg ggtcaacgga atccgcgccc accgaaaccg aattctcctc gaacaggcgg 5160

ctattaccac cacacctcgt aataacctta atccccgtag ttggcccgct gccctggtgt 5220

accaggaaag tcccgctccc accactgtgg tacttcccag agacgcccag gccgaagttc 5280

agatgactaa ctcaggggcg cagcttgcgg gcggctttcg tcacagggtg cggtcgcccg 5340

ggcgttttag ggcggagtaa cttgcatgta ttgggaattg tagttttttt aaaatgggaa 5400

gtgacgtatc gtgggaaaac ggaagtgaag atttgaggaa gttgtgggtt ttttggcttt 5460

cgtttctggg cgtaggttcg cgtgcggttt tctgggtgtt ttttgtggac tttaaccgtt 5520

acgtcatttt ttagtcctat atatactcgc tctgtacttg gcccttttta cactgtgact 5580

gattgagctg gtgccgtgtc gagtggtgtt ttttaatagg tttttttact ggtaaggctg 5640

actgttatgg ctgccgctgt ggaagcgctg tatgttgttc tggagcggga gggtgctatt 5700

ttgcctaggc aggagggttt ttcaggtgtt tatgtgtttt tctctcctat taattttgtt 5760

atacctccta tgggggctgt aatgttgtct ctacgcctgc gggtatgtat tcccccgggc 5820

tatttcggtc gctttttagc actgaccgat gttaaccaac ctgatgtgtt taccgagtct 5880

tacattatga ctccggacat gaccgaggaa ctgtcggtgg tgctttttaa tcacggtgac 5940

cagttttttt acggtcacgc cggcatggcc gtagtccgtc ttatgcttat aagggttgtt 6000

tttcctgttg taagacaggc ttctaatgtt taaatgtttt tttttttgtt attttatttt 6060

gtgtttaatg caggaacccg cagacatgtt tgagagaaaa atggtgtctt tttctgtggt 6120

ggttccggaa cttacctgcc tttatctgca tgagcatgac tacgatgtgc ttgctttttt 6180

gcgcgaggct ttgcctgatt ttttgagcag caccttgcat tttatatcgc cgcccatgca 6240

acaagcttac ataggggcta cgctggttag catagctccg agtatgcgtg tcataatcag 6300

tgtgggttct tttgtcatgg ttcctggcgg ggaagtggcc gcgctggtcc gtgcagacct 6360

gcacgattat gttcagctgg ccctgcgaag ggacctacgg gatcgcggta tttttgttaa 6420

tgttccgctt ttgaatctta tacaggtctg tgaggaacct gaatttttgc aatcatgatt 6480

cgctgcttga ggctgaaggt ggagggcgct ctggagcaga tttttacaat ggccggactt 6540

aatattcggg atttgcttag agacatattg ataaggtggc gagatgaaaa ttatttgggc 6600

atggttgaag gtgctggaat gtttatagag gagattcacc ctgaagggtt tagcctttac 6660

gtccacttgg acgtgagggc agtttgcctt ttggaagcca ttgtgcaaca tcttacaaat 6720

gccattatct gttctttggc tgtagagttt gaccacgcca ccggagggga gcgcgttcac 6780

ttaatagatc ttcattttga ggttttggat aatcttttgg aataaaaaaa aaaaaacatg 6840

gttcttccag ctcttcccgc tcctcccgtg tgtgactcgc agaacgaatg tgtaggttgg 6900

ctgggtgtgg cttattctgc ggtggtggat gttatcaggg cagcggcgca tgaaggagtt 6960

tacatagaac ccgaagccag ggggcgcctg gatgctttga gagagtggat atactacaac 7020

tactacacag agcgagctaa gcgacgagac cggagacgca gatctgtttg tcacgcccgc 7080

acctggtttt gcttcaggaa atatgactac gtccggcgtt ccatttggca tgacactacg 7140

accaacacga tctcggttgt ctcggcgcac tccgtacagt agggatcgcc tacctccttt 7200

tgagacagag acccgcgcta ccatactgga ggatcatccg ctgctgcccg aatgtaacac 7260

tttgacaatg cacaacgtga gttacgtgcg aggtcttccc tgcagtgtgg gatttacgct 7320

gattcaggaa tgggttgttc cctgggatat ggttctgacg cgggaggagc ttgtaatcct 7380

gaggaagtgt atgcacgtgt gcctgtgttg tgccaacatt gatatcatga cgagcatgat 7440

gatccatggt tacgagtcct gggctctcca ctgtcattgt tccagtcccg gttccctgca 7500

gtgcatagcc ggcgggcagg ttttggccag ctggtttagg atggtggtgg atggcgccat 7560

gtttaatcag aggtttatat ggtaccggga ggtggtgaat tacaacatgc caaaagaggt 7620

aatgtttatg tccagcgtgt ttatgagggg tcgccactta atctacctgc gcttgtggta 7680

tgatggccac gtgggttctg tggtccccgc catgagcttt ggatacagcg ccttgcactg 7740

tgggattttg aacaatattg tggtgctgtg ctgcagttac tgtgctgatt taagtgagat 7800

cagggtgcgc tgctgtgccc ggaggacaag gcgtctcatg ctgcgggcgg tgcgaatcat 7860

cgctgaggag accactgcca tgttgtattc ctgcaggacg gagcggcggc ggcagcagtt 7920

tattcgcgcg ctgctgcagc accaccgccc tatcctgatg cacgattatg actctacccc 7980

catgtaggcg tggacttccc cttcgccgcc cgttgagcaa ccgcaagttg gacagcagcc 8040

tgtggctcag cagctggaca gcgacatgaa cttaagcgag ctgcccgggg agtttattaa 8100

tatcactgat gagcgtttgg ctcgacagga aaccgtgtgg aatataacac ctaagaatat 8160

gtctgttacc catgatatga tgctttttaa ggccagccgg ggagaaagga ctgtgtactc 8220

tgtgtgttgg gagggaggtg gcaggttgaa tactagggtt ctgtgagttt gattaaggta 8280

cggtgatcaa tataagctat gtggtggtgg ggctatacta ctgaatgaaa aatgacttga 8340

aattttctgc aattgaaaaa taaacacgtt gaaacataac atgcaacagg ttcacgattc 8400

tttattcctg ggcaatgtag gagaaggtgt aagagttggt agcaaaagtt tcagtggtgt 8460

attttccact ttcccaggac catgtaaaag acatagagta agtgcttacc tcgctagttt 8520

ctgtggattc actagaatcg atgtaggatg ttgcccctcc tgacgcggta ggagaagggg 8580

agggtgccct gcatgtctgc cgctgctctt gctcttgccg ctgctgagga ggggggcgca 8640

tctgccgcag caccggatgc atctgggaaa agcaaaaaag gggctcgtcc ctgtttccgg 8700

aggaatttgc aagcggggtc ttgcatgacg gggaggcaaa cccccgttcg ccgcagtccg 8760

gccggcccga gactcgaacc gggggtcctg cgactcaacc cttggaaaat aaccctccgg 8820

ctacagggag cgagccactt aatgctttcg ctttccagcc taaccgctta cgccgcgcgc 8880

ggccagtggc caaaaaagct agcgcagcag ccgccgcgcc tggaaggaag ccaaaaggag 8940

cgctcccccg ttgtctgacg tcgcacacct gggttcgaca cgcgggcggt aaccgcatgg 9000

atcacggcgg acggccggat ccggggttcg aaccccggtc gtccgccatg atacccttgc 9060

gaatttatcc accagaccac ggaagagtgc ccgcttacag gctctccttt tgcacggtct 9120

agagcgtcaa cgactgcgca cgcctcaccg gccagagcgt cccgaccatg gagcactttt 9180

tgccgctgcg caacatctgg aaccgcgtcc gcgactttcc gcgcgcctcc accaccgccg 9240

ccggcatcac ctggatgtcc aggtacatct acggattacg tcgacgttta aaccatatga 9300

tcagctcact caaaggcggt aatacggtta tccacagaat caggggataa cgcaggaaag 9360

aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc gttgctggcg 9420

tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc aagtcagagg 9480

tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag ctccctcgtg 9540

cgctctcctg ttccgaccct gccgcttacc ggatacctgt ccgcctttct cccttcggga 9600

agcgtggcgc tttctcatag ctcacgctgt aggtatctca gttcggtgta ggtcgttcgc 9660

tccaagctgg gctgtgtgca cgaacccccc gttcagcccg accgctgcgc cttatccggt 9720

aactatcgtc ttgagtccaa cccggtaaga cacgacttat cgccactggc agcagccact 9780

ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt gaagtggtgg 9840

cctaactacg gctacactag aagaacagta tttggtatct gcgctctgct gaagccagtt 9900

accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc tggtagcggt 9960

ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca agaagatcct 10020

ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta agggattttg 10080

gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa atgaagtttt 10140

aaatcaatct aaagtatata tgagtaaact tggtctgaca gttagaaaaa ctcatcgagc 10200

atcaaatgaa actgcaattt attcatatca ggattatcaa taccatattt ttgaaaaagc 10260

cgtttctgta atgaaggaga aaactcaccg aggcagttcc ataggatggc aagatcctgg 10320

tatcggtctg cgattccgac tcgtccaaca tcaatacaac ctattaattt cccctcgtca 10380

aaaataaggt tatcaagtga gaaatcacca tgagtgacga ctgaatccgg tgagaatggc 10440

aaaagtttat gcatttcttt ccagacttgt tcaacaggcc agccattacg ctcgtcatca 10500

aaatcactcg catcaaccaa accgttattc attcgtgatt gcgcctgagc gagacgaaat 10560

acgcgatcgc tgttaaaagg acaattacaa acaggaatcg aatgcaaccg gcgcaggaac 10620

actgccagcg catcaacaat attttcacct gaatcaggat attcttctaa tacctggaat 10680

gctgttttcc cagggatcgc agtggtgagt aaccatgcat catcaggagt acggataaaa 10740

tgcttgatgg tcggaagagg cataaattcc gtcagccagt ttagtctgac catctcatct 10800

gtaacatcat tggcaacgct acctttgcca tgtttcagaa acaactctgg cgcatcgggc 10860

ttcccataca atcgatagat tgtcgcacct gattgcccga cattatcgcg agcccattta 10920

tacccatata aatcagcatc catgttggaa tttaatcgcg gcctagagca agacgtttcc 10980

cgttgaatat ggctcatact cttccttttt caatattatt gaagcattta tcagggttat 11040

tgtctcatga gcggatacat atttgaatgt atttagaaaa ataaacaaat aggggttccg 11100

cgcacatttc cccgaaaagt gccacctgac gtctaagaaa ccattattat catgacatta 11160

acctataaaa ataggcgtat cacgaggccc tttcgtctcg cgcgtttcgg tgatgacggt 11220

gaaaacctct gacacatgca gctcccggag acggtcacag cttgtctgta agcggatgcc 11280

gggagcagac aacaacgtca aagggcgaaa aaccgtctat cagggcgatg gcccactacg 11340

tgaaccatca ccctaatcaa gttttttggg gtcgaggtgc cgtaaagcac taaatcggaa 11400

ccctaaaggg agcccccgat ttagagcttg acggggaaag ccggcgaacg tggcgagaaa 11460

ggaagggaag aaagcgaaag gagcgggcgc tagggcgctg gcaagtgtag cggtcacgct 11520

gcgcgtaacc accacacccg ccgcgcttaa tgcgccgcta cagggcgcga tggatcc 11577

<210> 93

<211> 4443

<212> DNA

<213> 人工序列

<220>

<223> CFTR

<400> 93

atgcagagaa gccccctgga gaaggcctct gtggtgagca agctgttctt cagctggacc 60

agacccatcc tgagaaaggg ctacagacag agactggagc tgtctgacat ctaccagatc 120

ccctctgtgg actctgctga caacctgtct gagaagctgg agagagagtg ggacagagag 180

ctggccagca agaagaaccc caagctgatc aatgccctga gaagatgctt cttctggaga 240

ttcatgttct atggcatctt cctgtacctg ggggaggtga ccaaggctgt gcagcccctg 300

ctgctgggca gaatcattgc cagctatgac cctgacaaca aggaggagag aagcattgcc 360

atctacctgg gcattggcct gtgcctgctg ttcattgtga gaaccctgct gctgcaccct 420

gccatctttg gcctgcacca cattggcatg cagatgagaa ttgccatgtt cagcctgatc 480

tacaagaaga ccctgaagct gagcagcaga gtgctggaca agatcagcat tggccagctg 540

gtgagcctgc tgagcaacaa cctgaacaag tttgatgagg gcctggccct ggcccacttt 600

gtgtggattg cccccctgca ggtggccctg ctgatgggcc tgatctggga gctgctgcag 660

gcctctgcct tctgtggcct gggcttcctg attgtgctgg ccctgttcca ggctggcctg 720

ggcagaatga tgatgaagta cagagaccag agagctggca agatctctga gagactggtg 780

atcacctctg agatgattga gaacatccag tctgtgaagg cctactgctg ggaggaggcc 840

atggagaaga tgattgagaa cctgagacag acagagctga agctgaccag aaaggctgcc 900

tatgtgagat acttcaacag ctctgccttc ttcttctctg gcttctttgt ggtgttcctg 960

tctgtgctgc cctatgccct gatcaagggc atcatcctga gaaagatctt caccaccatc 1020

agcttctgca ttgtgctgag aatggctgtg accagacagt tcccctgggc tgtgcagacc 1080

tggtatgaca gcctgggggc catcaacaag atccaggact tcctgcagaa gcaggagtac 1140

aagaccctgg agtacaacct gaccaccaca gaggtggtga tggagaatgt gacagccttc 1200

tgggaggagg gctttgggga gctgtttgag aaggccaagc agaacaacaa caacagaaag 1260

accagcaatg gggatgacag cctgttcttc agcaacttca gcctgctggg cacccctgtg 1320

ctgaaggaca tcaacttcaa gattgagaga ggccagctgc tggctgtggc tggcagcaca 1380

ggggctggca agaccagcct gctgatgatg atcatggggg agctggagcc ctctgagggc 1440

aagatcaagc actctggcag aatcagcttc tgcagccagt tcagctggat catgcctggc 1500

accatcaagg agaacatcat ctttggggtg agctatgatg agtacagata cagatctgtg 1560

atcaaggcct gccagctgga ggaggacatc agcaagtttg ctgagaagga caacattgtg 1620

ctgggggagg ggggcatcac cctgtctggg ggccagagag ccagaatcag cctggccaga 1680

gctgtgtaca aggatgctga cctgtacctg ctggacagcc cctttggcta cctggatgtg 1740

ctgacagaga aggagatctt tgagagctgt gtgtgcaagc tgatggccaa caagaccaga 1800

atcctggtga ccagcaagat ggagcacctg aagaaggctg acaagatcct gatcctgcat 1860

gagggcagca gctacttcta tggcaccttc tctgagctgc agaacctgca gcctgacttc 1920

agcagcaagc tgatgggctg tgacagcttt gaccagttct ctgctgagag aagaaacagc 1980

atcctgacag agaccctgca cagattcagc ctggaggggg atgcccctgt gagctggaca 2040

gagaccaaga agcagagctt caagcagaca ggggagtttg gggagaagag aaagaacagc 2100

atcctgaacc ccatcaacag catcagaaag ttcagcattg tgcagaagac ccccctgcag 2160

atgaatggca ttgaggagga ctctgatgag cccctggaga gaagactgag cctggtgcct 2220

gactctgagc agggggaggc catcctgccc agaatctctg tgatcagcac aggccccacc 2280

ctgcaggcca gaagaagaca gtctgtgctg aacctgatga cccactctgt gaaccagggc 2340

cagaacatcc acagaaagac cacagccagc accagaaagg tgagcctggc cccccaggcc 2400

aacctgacag agctggacat ctacagcaga agactgagcc aggagacagg cctggagatc 2460

tctgaggaga tcaatgagga ggacctgaag gagtgcttct ttgatgacat ggagagcatc 2520

cctgctgtga ccacctggaa cacctacctg agatacatca cagtgcacaa gagcctgatc 2580

tttgtgctga tctggtgcct ggtgatcttc ctggctgagg tggctgccag cctggtggtg 2640

ctgtggctgc tgggcaacac ccccctgcag gacaagggca acagcaccca cagcagaaac 2700

aacagctatg ctgtgatcat caccagcacc agcagctact atgtgttcta catctatgtg 2760

ggggtggctg acaccctgct ggccatgggc ttcttcagag gcctgcccct ggtgcacacc 2820

ctgatcacag tgagcaagat cctgcaccac aagatgctgc actctgtgct gcaggccccc 2880

atgagcaccc tgaacaccct gaaggctggg ggcatcctga acagattcag caaggacatt 2940

gccatcctgg atgacctgct gcccctgacc atctttgact tcatccagct gctgctgatt 3000

gtgattgggg ccattgctgt ggtggctgtg ctgcagccct acatctttgt ggccacagtg 3060

cctgtgattg tggccttcat catgctgaga gcctacttcc tgcagaccag ccagcagctg 3120

aagcagctgg agtctgaggg cagaagcccc atcttcaccc acctggtgac cagcctgaag 3180

ggcctgtgga ccctgagagc ctttggcaga cagccctact ttgagaccct gttccacaag 3240

gccctgaacc tgcacacagc caactggttc ctgtacctga gcaccctgag atggttccag 3300

atgagaattg agatgatctt tgtgatcttc ttcattgctg tgaccttcat cagcatcctg 3360

accacagggg agggggaggg cagagtgggc atcatcctga ccctggccat gaacatcatg 3420

agcaccctgc agtgggctgt gaacagcagc attgatgtgg acagcctgat gagatctgtg 3480

agcagagtgt tcaagttcat tgacatgccc acagagggca agcccaccaa gagcaccaag 3540

ccctacaaga atggccagct gagcaaggtg atgatcattg agaacagcca tgtgaagaag 3600

gatgacatct ggccctctgg gggccagatg acagtgaagg acctgacagc caagtacaca 3660

gaggggggca atgccatcct ggagaacatc agcttcagca tcagccctgg ccagagagtg 3720

ggcctgctgg gcagaacagg ctctggcaag agcaccctgc tgtctgcctt cctgagactg 3780

ctgaacacag agggggagat ccagattgat ggggtgagct gggacagcat caccctgcag 3840

cagtggagaa aggcctttgg ggtgatcccc cagaaggtgt tcatcttctc tggcaccttc 3900

agaaagaacc tggaccccta tgagcagtgg tctgaccagg agatctggaa ggtggctgat 3960

gaggtgggcc tgagatctgt gattgagcag ttccctggca agctggactt tgtgctggtg 4020

gatgggggct gtgtgctgag ccatggccac aagcagctga tgtgcctggc cagatctgtg 4080

ctgagcaagg ccaagatcct gctgctggat gagccctctg cccacctgga ccctgtgacc 4140

taccagatca tcagaagaac cctgaagcag gcctttgctg actgcacagt gatcctgtgt 4200

gagcacagaa ttgaggccat gctggagtgc cagcagttcc tggtgattga ggagaacaag 4260

gtgagacagt atgacagcat ccagaagctg ctgaatgaga gaagcctgtt cagacaggcc 4320

atcagcccct ctgacagagt gaagctgttc ccccacagaa acagcagcaa gtgcaagagc 4380

aagccccaga ttgctgccct gaaggaggag accgaggagg aggtgcagga caccagactg 4440

taa 4443

<210> 94

<211> 1480

<212> PRT

<213> 人工序列

<220>

<223> CFTR蛋白

<400> 94

Met Gln Arg Ser Pro Leu Glu Lys Ala Ser Val Val Ser Lys Leu Phe

1 5 10 15

Phe Ser Trp Thr Arg Pro Ile Leu Arg Lys Gly Tyr Arg Gln Arg Leu

20 25 30

Glu Leu Ser Asp Ile Tyr Gln Ile Pro Ser Val Asp Ser Ala Asp Asn

35 40 45

Leu Ser Glu Lys Leu Glu Arg Glu Trp Asp Arg Glu Leu Ala Ser Lys

50 55 60

Lys Asn Pro Lys Leu Ile Asn Ala Leu Arg Arg Cys Phe Phe Trp Arg

65 70 75 80

Phe Met Phe Tyr Gly Ile Phe Leu Tyr Leu Gly Glu Val Thr Lys Ala

85 90 95

Val Gln Pro Leu Leu Leu Gly Arg Ile Ile Ala Ser Tyr Asp Pro Asp

100 105 110

Asn Lys Glu Glu Arg Ser Ile Ala Ile Tyr Leu Gly Ile Gly Leu Cys

115 120 125

Leu Leu Phe Ile Val Arg Thr Leu Leu Leu His Pro Ala Ile Phe Gly

130 135 140

Leu His His Ile Gly Met Gln Met Arg Ile Ala Met Phe Ser Leu Ile

145 150 155 160

Tyr Lys Lys Thr Leu Lys Leu Ser Ser Arg Val Leu Asp Lys Ile Ser

165 170 175

Ile Gly Gln Leu Val Ser Leu Leu Ser Asn Asn Leu Asn Lys Phe Asp

180 185 190

Glu Gly Leu Ala Leu Ala His Phe Val Trp Ile Ala Pro Leu Gln Val

195 200 205

Ala Leu Leu Met Gly Leu Ile Trp Glu Leu Leu Gln Ala Ser Ala Phe

210 215 220

Cys Gly Leu Gly Phe Leu Ile Val Leu Ala Leu Phe Gln Ala Gly Leu

225 230 235 240

Gly Arg Met Met Met Lys Tyr Arg Asp Gln Arg Ala Gly Lys Ile Ser

245 250 255

Glu Arg Leu Val Ile Thr Ser Glu Met Ile Glu Asn Ile Gln Ser Val

260 265 270

Lys Ala Tyr Cys Trp Glu Glu Ala Met Glu Lys Met Ile Glu Asn Leu

275 280 285

Arg Gln Thr Glu Leu Lys Leu Thr Arg Lys Ala Ala Tyr Val Arg Tyr

290 295 300

Phe Asn Ser Ser Ala Phe Phe Phe Ser Gly Phe Phe Val Val Phe Leu

305 310 315 320

Ser Val Leu Pro Tyr Ala Leu Ile Lys Gly Ile Ile Leu Arg Lys Ile

325 330 335

Phe Thr Thr Ile Ser Phe Cys Ile Val Leu Arg Met Ala Val Thr Arg

340 345 350

Gln Phe Pro Trp Ala Val Gln Thr Trp Tyr Asp Ser Leu Gly Ala Ile

355 360 365

Asn Lys Ile Gln Asp Phe Leu Gln Lys Gln Glu Tyr Lys Thr Leu Glu

370 375 380

Tyr Asn Leu Thr Thr Thr Glu Val Val Met Glu Asn Val Thr Ala Phe

385 390 395 400

Trp Glu Glu Gly Phe Gly Glu Leu Phe Glu Lys Ala Lys Gln Asn Asn

405 410 415

Asn Asn Arg Lys Thr Ser Asn Gly Asp Asp Ser Leu Phe Phe Ser Asn

420 425 430

Phe Ser Leu Leu Gly Thr Pro Val Leu Lys Asp Ile Asn Phe Lys Ile

435 440 445

Glu Arg Gly Gln Leu Leu Ala Val Ala Gly Ser Thr Gly Ala Gly Lys

450 455 460

Thr Ser Leu Leu Met Met Ile Met Gly Glu Leu Glu Pro Ser Glu Gly

465 470 475 480

Lys Ile Lys His Ser Gly Arg Ile Ser Phe Cys Ser Gln Phe Ser Trp

485 490 495

Ile Met Pro Gly Thr Ile Lys Glu Asn Ile Ile Phe Gly Val Ser Tyr

500 505 510

Asp Glu Tyr Arg Tyr Arg Ser Val Ile Lys Ala Cys Gln Leu Glu Glu

515 520 525

Asp Ile Ser Lys Phe Ala Glu Lys Asp Asn Ile Val Leu Gly Glu Gly

530 535 540

Gly Ile Thr Leu Ser Gly Gly Gln Arg Ala Arg Ile Ser Leu Ala Arg

545 550 555 560

Ala Val Tyr Lys Asp Ala Asp Leu Tyr Leu Leu Asp Ser Pro Phe Gly

565 570 575

Tyr Leu Asp Val Leu Thr Glu Lys Glu Ile Phe Glu Ser Cys Val Cys

580 585 590

Lys Leu Met Ala Asn Lys Thr Arg Ile Leu Val Thr Ser Lys Met Glu

595 600 605

His Leu Lys Lys Ala Asp Lys Ile Leu Ile Leu His Glu Gly Ser Ser

610 615 620

Tyr Phe Tyr Gly Thr Phe Ser Glu Leu Gln Asn Leu Gln Pro Asp Phe

625 630 635 640

Ser Ser Lys Leu Met Gly Cys Asp Ser Phe Asp Gln Phe Ser Ala Glu

645 650 655

Arg Arg Asn Ser Ile Leu Thr Glu Thr Leu His Arg Phe Ser Leu Glu

660 665 670

Gly Asp Ala Pro Val Ser Trp Thr Glu Thr Lys Lys Gln Ser Phe Lys

675 680 685

Gln Thr Gly Glu Phe Gly Glu Lys Arg Lys Asn Ser Ile Leu Asn Pro

690 695 700

Ile Asn Ser Ile Arg Lys Phe Ser Ile Val Gln Lys Thr Pro Leu Gln

705 710 715 720

Met Asn Gly Ile Glu Glu Asp Ser Asp Glu Pro Leu Glu Arg Arg Leu

725 730 735

Ser Leu Val Pro Asp Ser Glu Gln Gly Glu Ala Ile Leu Pro Arg Ile

740 745 750

Ser Val Ile Ser Thr Gly Pro Thr Leu Gln Ala Arg Arg Arg Gln Ser

755 760 765

Val Leu Asn Leu Met Thr His Ser Val Asn Gln Gly Gln Asn Ile His

770 775 780

Arg Lys Thr Thr Ala Ser Thr Arg Lys Val Ser Leu Ala Pro Gln Ala

785 790 795 800

Asn Leu Thr Glu Leu Asp Ile Tyr Ser Arg Arg Leu Ser Gln Glu Thr

805 810 815

Gly Leu Glu Ile Ser Glu Glu Ile Asn Glu Glu Asp Leu Lys Glu Cys

820 825 830

Phe Phe Asp Asp Met Glu Ser Ile Pro Ala Val Thr Thr Trp Asn Thr

835 840 845

Tyr Leu Arg Tyr Ile Thr Val His Lys Ser Leu Ile Phe Val Leu Ile

850 855 860

Trp Cys Leu Val Ile Phe Leu Ala Glu Val Ala Ala Ser Leu Val Val

865 870 875 880

Leu Trp Leu Leu Gly Asn Thr Pro Leu Gln Asp Lys Gly Asn Ser Thr

885 890 895

His Ser Arg Asn Asn Ser Tyr Ala Val Ile Ile Thr Ser Thr Ser Ser

900 905 910

Tyr Tyr Val Phe Tyr Ile Tyr Val Gly Val Ala Asp Thr Leu Leu Ala

915 920 925

Met Gly Phe Phe Arg Gly Leu Pro Leu Val His Thr Leu Ile Thr Val

930 935 940

Ser Lys Ile Leu His His Lys Met Leu His Ser Val Leu Gln Ala Pro

945 950 955 960

Met Ser Thr Leu Asn Thr Leu Lys Ala Gly Gly Ile Leu Asn Arg Phe

965 970 975

Ser Lys Asp Ile Ala Ile Leu Asp Asp Leu Leu Pro Leu Thr Ile Phe

980 985 990

Asp Phe Ile Gln Leu Leu Leu Ile Val Ile Gly Ala Ile Ala Val Val

995 1000 1005

Ala Val Leu Gln Pro Tyr Ile Phe Val Ala Thr Val Pro Val Ile

1010 1015 1020

Val Ala Phe Ile Met Leu Arg Ala Tyr Phe Leu Gln Thr Ser Gln

1025 1030 1035

Gln Leu Lys Gln Leu Glu Ser Glu Gly Arg Ser Pro Ile Phe Thr

1040 1045 1050

His Leu Val Thr Ser Leu Lys Gly Leu Trp Thr Leu Arg Ala Phe

1055 1060 1065

Gly Arg Gln Pro Tyr Phe Glu Thr Leu Phe His Lys Ala Leu Asn

1070 1075 1080

Leu His Thr Ala Asn Trp Phe Leu Tyr Leu Ser Thr Leu Arg Trp

1085 1090 1095

Phe Gln Met Arg Ile Glu Met Ile Phe Val Ile Phe Phe Ile Ala

1100 1105 1110

Val Thr Phe Ile Ser Ile Leu Thr Thr Gly Glu Gly Glu Gly Arg

1115 1120 1125

Val Gly Ile Ile Leu Thr Leu Ala Met Asn Ile Met Ser Thr Leu

1130 1135 1140

Gln Trp Ala Val Asn Ser Ser Ile Asp Val Asp Ser Leu Met Arg

1145 1150 1155

Ser Val Ser Arg Val Phe Lys Phe Ile Asp Met Pro Thr Glu Gly

1160 1165 1170

Lys Pro Thr Lys Ser Thr Lys Pro Tyr Lys Asn Gly Gln Leu Ser

1175 1180 1185

Lys Val Met Ile Ile Glu Asn Ser His Val Lys Lys Asp Asp Ile

1190 1195 1200

Trp Pro Ser Gly Gly Gln Met Thr Val Lys Asp Leu Thr Ala Lys

1205 1210 1215

Tyr Thr Glu Gly Gly Asn Ala Ile Leu Glu Asn Ile Ser Phe Ser

1220 1225 1230

Ile Ser Pro Gly Gln Arg Val Gly Leu Leu Gly Arg Thr Gly Ser

1235 1240 1245

Gly Lys Ser Thr Leu Leu Ser Ala Phe Leu Arg Leu Leu Asn Thr

1250 1255 1260

Glu Gly Glu Ile Gln Ile Asp Gly Val Ser Trp Asp Ser Ile Thr

1265 1270 1275

Leu Gln Gln Trp Arg Lys Ala Phe Gly Val Ile Pro Gln Lys Val

1280 1285 1290

Phe Ile Phe Ser Gly Thr Phe Arg Lys Asn Leu Asp Pro Tyr Glu

1295 1300 1305

Gln Trp Ser Asp Gln Glu Ile Trp Lys Val Ala Asp Glu Val Gly

1310 1315 1320

Leu Arg Ser Val Ile Glu Gln Phe Pro Gly Lys Leu Asp Phe Val

1325 1330 1335

Leu Val Asp Gly Gly Cys Val Leu Ser His Gly His Lys Gln Leu

1340 1345 1350

Met Cys Leu Ala Arg Ser Val Leu Ser Lys Ala Lys Ile Leu Leu

1355 1360 1365

Leu Asp Glu Pro Ser Ala His Leu Asp Pro Val Thr Tyr Gln Ile

1370 1375 1380

Ile Arg Arg Thr Leu Lys Gln Ala Phe Ala Asp Cys Thr Val Ile

1385 1390 1395

Leu Cys Glu His Arg Ile Glu Ala Met Leu Glu Cys Gln Gln Phe

1400 1405 1410

Leu Val Ile Glu Glu Asn Lys Val Arg Gln Tyr Asp Ser Ile Gln

1415 1420 1425

Lys Leu Leu Asn Glu Arg Ser Leu Phe Arg Gln Ala Ile Ser Pro

1430 1435 1440

Ser Asp Arg Val Lys Leu Phe Pro His Arg Asn Ser Ser Lys Cys

1445 1450 1455

Lys Ser Lys Pro Gln Ile Ala Ala Leu Lys Glu Glu Thr Glu Glu

1460 1465 1470

Glu Val Gln Asp Thr Arg Leu

1475 1480

<210> 95

<211> 1428

<212> PRT

<213> 人工序列

<220>

<223> CFTR△R蛋白

<400> 95

Met Gln Arg Ser Pro Leu Glu Lys Ala Ser Val Val Ser Lys Leu Phe

1 5 10 15

Phe Ser Trp Thr Arg Pro Ile Leu Arg Lys Gly Tyr Arg Gln Arg Leu

20 25 30

Glu Leu Ser Asp Ile Tyr Gln Ile Pro Ser Val Asp Ser Ala Asp Asn

35 40 45

Leu Ser Glu Lys Leu Glu Arg Glu Trp Asp Arg Glu Leu Ala Ser Lys

50 55 60

Lys Asn Pro Lys Leu Ile Asn Ala Leu Arg Arg Cys Phe Phe Trp Arg

65 70 75 80

Phe Met Phe Tyr Gly Ile Phe Leu Tyr Leu Gly Glu Val Thr Lys Ala

85 90 95

Val Gln Pro Leu Leu Leu Gly Arg Ile Ile Ala Ser Tyr Asp Pro Asp

100 105 110

Asn Lys Glu Glu Arg Ser Ile Ala Ile Tyr Leu Gly Ile Gly Leu Cys

115 120 125

Leu Leu Phe Ile Val Arg Thr Leu Leu Leu His Pro Ala Ile Phe Gly

130 135 140

Leu His His Ile Gly Met Gln Met Arg Ile Ala Met Phe Ser Leu Ile

145 150 155 160

Tyr Lys Lys Thr Leu Lys Leu Ser Ser Arg Val Leu Asp Lys Ile Ser

165 170 175

Ile Gly Gln Leu Val Ser Leu Leu Ser Asn Asn Leu Asn Lys Phe Asp

180 185 190

Glu Gly Leu Ala Leu Ala His Phe Val Trp Ile Ala Pro Leu Gln Val

195 200 205

Ala Leu Leu Met Gly Leu Ile Trp Glu Leu Leu Gln Ala Ser Ala Phe

210 215 220

Cys Gly Leu Gly Phe Leu Ile Val Leu Ala Leu Phe Gln Ala Gly Leu

225 230 235 240

Gly Arg Met Met Met Lys Tyr Arg Asp Gln Arg Ala Gly Lys Ile Ser

245 250 255

Glu Arg Leu Val Ile Thr Ser Glu Met Ile Glu Asn Ile Gln Ser Val

260 265 270

Lys Ala Tyr Cys Trp Glu Glu Ala Met Glu Lys Met Ile Glu Asn Leu

275 280 285

Arg Gln Thr Glu Leu Lys Leu Thr Arg Lys Ala Ala Tyr Val Arg Tyr

290 295 300

Phe Asn Ser Ser Ala Phe Phe Phe Ser Gly Phe Phe Val Val Phe Leu

305 310 315 320

Ser Val Leu Pro Tyr Ala Leu Ile Lys Gly Ile Ile Leu Arg Lys Ile

325 330 335

Phe Thr Thr Ile Ser Phe Cys Ile Val Leu Arg Met Ala Val Thr Arg

340 345 350

Gln Phe Pro Trp Ala Val Gln Thr Trp Tyr Asp Ser Leu Gly Ala Ile

355 360 365

Asn Lys Ile Gln Asp Phe Leu Gln Lys Gln Glu Tyr Lys Thr Leu Glu

370 375 380

Tyr Asn Leu Thr Thr Thr Glu Val Val Met Glu Asn Val Thr Ala Phe

385 390 395 400

Trp Glu Glu Gly Phe Gly Glu Leu Phe Glu Lys Ala Lys Gln Asn Asn

405 410 415

Asn Asn Arg Lys Thr Ser Asn Gly Asp Asp Ser Leu Phe Phe Ser Asn

420 425 430

Phe Ser Leu Leu Gly Thr Pro Val Leu Lys Asp Ile Asn Phe Lys Ile

435 440 445

Glu Arg Gly Gln Leu Leu Ala Val Ala Gly Ser Thr Gly Ala Gly Lys

450 455 460

Thr Ser Leu Leu Met Met Ile Met Gly Glu Leu Glu Pro Ser Glu Gly

465 470 475 480

Lys Ile Lys His Ser Gly Arg Ile Ser Phe Cys Ser Gln Phe Ser Trp

485 490 495

Ile Met Pro Gly Thr Ile Lys Glu Asn Ile Ile Phe Gly Val Ser Tyr

500 505 510

Asp Glu Tyr Arg Tyr Arg Ser Val Ile Lys Ala Cys Gln Leu Glu Glu

515 520 525

Asp Ile Ser Lys Phe Ala Glu Lys Asp Asn Ile Val Leu Gly Glu Gly

530 535 540

Gly Ile Thr Leu Ser Gly Gly Gln Arg Ala Arg Ile Ser Leu Ala Arg

545 550 555 560

Ala Val Tyr Lys Asp Ala Asp Leu Tyr Leu Leu Asp Ser Pro Phe Gly

565 570 575

Tyr Leu Asp Val Leu Thr Glu Lys Glu Ile Phe Glu Ser Cys Val Cys

580 585 590

Lys Leu Met Ala Asn Lys Thr Arg Ile Leu Val Thr Ser Lys Met Glu

595 600 605

His Leu Lys Lys Ala Asp Lys Ile Leu Ile Leu His Glu Gly Ser Ser

610 615 620

Tyr Phe Tyr Gly Thr Phe Ser Glu Leu Gln Asn Leu Gln Pro Asp Phe

625 630 635 640

Ser Ser Lys Leu Met Gly Cys Asp Ser Phe Asp Gln Phe Ser Ala Glu

645 650 655

Arg Arg Asn Ser Ile Leu Thr Glu Thr Leu His Arg Phe Ser Leu Glu

660 665 670

Gly Asp Ala Pro Val Ser Trp Thr Glu Thr Lys Lys Gln Ser Phe Lys

675 680 685

Gln Thr Gly Glu Phe Gly Glu Lys Arg Lys Asn Ser Ile Leu Asn Pro

690 695 700

Ile Asn Ser Thr Leu Gln Ala Arg Arg Arg Gln Ser Val Leu Asn Leu

705 710 715 720

Met Thr His Ser Val Asn Gln Gly Gln Asn Ile His Arg Lys Thr Thr

725 730 735

Ala Ser Thr Arg Lys Val Ser Leu Ala Pro Gln Ala Asn Leu Thr Glu

740 745 750

Leu Asp Ile Tyr Ser Arg Arg Leu Ser Gln Glu Thr Gly Leu Glu Ile

755 760 765

Ser Glu Glu Ile Asn Glu Glu Asp Leu Lys Glu Cys Phe Phe Asp Asp

770 775 780

Met Glu Ser Ile Pro Ala Val Thr Thr Trp Asn Thr Tyr Leu Arg Tyr

785 790 795 800

Ile Thr Val His Lys Ser Leu Ile Phe Val Leu Ile Trp Cys Leu Val

805 810 815

Ile Phe Leu Ala Glu Val Ala Ala Ser Leu Val Val Leu Trp Leu Leu

820 825 830

Gly Asn Thr Pro Leu Gln Asp Lys Gly Asn Ser Thr His Ser Arg Asn

835 840 845

Asn Ser Tyr Ala Val Ile Ile Thr Ser Thr Ser Ser Tyr Tyr Val Phe

850 855 860

Tyr Ile Tyr Val Gly Val Ala Asp Thr Leu Leu Ala Met Gly Phe Phe

865 870 875 880

Arg Gly Leu Pro Leu Val His Thr Leu Ile Thr Val Ser Lys Ile Leu

885 890 895

His His Lys Met Leu His Ser Val Leu Gln Ala Pro Met Ser Thr Leu

900 905 910

Asn Thr Leu Lys Ala Gly Gly Ile Leu Asn Arg Phe Ser Lys Asp Ile

915 920 925

Ala Ile Leu Asp Asp Leu Leu Pro Leu Thr Ile Phe Asp Phe Ile Gln

930 935 940

Leu Leu Leu Ile Val Ile Gly Ala Ile Ala Val Val Ala Val Leu Gln

945 950 955 960

Pro Tyr Ile Phe Val Ala Thr Val Pro Val Ile Val Ala Phe Ile Met

965 970 975

Leu Arg Ala Tyr Phe Leu Gln Thr Ser Gln Gln Leu Lys Gln Leu Glu

980 985 990

Ser Glu Gly Arg Ser Pro Ile Phe Thr His Leu Val Thr Ser Leu Lys

995 1000 1005

Gly Leu Trp Thr Leu Arg Ala Phe Gly Arg Gln Pro Tyr Phe Glu

1010 1015 1020

Thr Leu Phe His Lys Ala Leu Asn Leu His Thr Ala Asn Trp Phe

1025 1030 1035

Leu Tyr Leu Ser Thr Leu Arg Trp Phe Gln Met Arg Ile Glu Met

1040 1045 1050

Ile Phe Val Ile Phe Phe Ile Ala Val Thr Phe Ile Ser Ile Leu

1055 1060 1065

Thr Thr Gly Glu Gly Glu Gly Arg Val Gly Ile Ile Leu Thr Leu

1070 1075 1080

Ala Met Asn Ile Met Ser Thr Leu Gln Trp Ala Val Asn Ser Ser

1085 1090 1095

Ile Asp Val Asp Ser Leu Met Arg Ser Val Ser Arg Val Phe Lys

1100 1105 1110

Phe Ile Asp Met Pro Thr Glu Gly Lys Pro Thr Lys Ser Thr Lys

1115 1120 1125

Pro Tyr Lys Asn Gly Gln Leu Ser Lys Val Met Ile Ile Glu Asn

1130 1135 1140

Ser His Val Lys Lys Asp Asp Ile Trp Pro Ser Gly Gly Gln Met

1145 1150 1155

Thr Val Lys Asp Leu Thr Ala Lys Tyr Thr Glu Gly Gly Asn Ala

1160 1165 1170

Ile Leu Glu Asn Ile Ser Phe Ser Ile Ser Pro Gly Gln Arg Val

1175 1180 1185

Gly Leu Leu Gly Arg Thr Gly Ser Gly Lys Ser Thr Leu Leu Ser

1190 1195 1200

Ala Phe Leu Arg Leu Leu Asn Thr Glu Gly Glu Ile Gln Ile Asp

1205 1210 1215

Gly Val Ser Trp Asp Ser Ile Thr Leu Gln Gln Trp Arg Lys Ala

1220 1225 1230

Phe Gly Val Ile Pro Gln Lys Val Phe Ile Phe Ser Gly Thr Phe

1235 1240 1245

Arg Lys Asn Leu Asp Pro Tyr Glu Gln Trp Ser Asp Gln Glu Ile

1250 1255 1260

Trp Lys Val Ala Asp Glu Val Gly Leu Arg Ser Val Ile Glu Gln

1265 1270 1275

Phe Pro Gly Lys Leu Asp Phe Val Leu Val Asp Gly Gly Cys Val

1280 1285 1290

Leu Ser His Gly His Lys Gln Leu Met Cys Leu Ala Arg Ser Val

1295 1300 1305

Leu Ser Lys Ala Lys Ile Leu Leu Leu Asp Glu Pro Ser Ala His

1310 1315 1320

Leu Asp Pro Val Thr Tyr Gln Ile Ile Arg Arg Thr Leu Lys Gln

1325 1330 1335

Ala Phe Ala Asp Cys Thr Val Ile Leu Cys Glu His Arg Ile Glu

1340 1345 1350

Ala Met Leu Glu Cys Gln Gln Phe Leu Val Ile Glu Glu Asn Lys

1355 1360 1365

Val Arg Gln Tyr Asp Ser Ile Gln Lys Leu Leu Asn Glu Arg Ser

1370 1375 1380

Leu Phe Arg Gln Ala Ile Ser Pro Ser Asp Arg Val Lys Leu Phe

1385 1390 1395

Pro His Arg Asn Ser Ser Lys Cys Lys Ser Lys Pro Gln Ile Ala

1400 1405 1410

Ala Leu Lys Glu Glu Thr Glu Glu Glu Val Gln Asp Thr Arg Leu

1415 1420 1425

<210> 96

<211> 250

<212> DNA

<213> 人工序列

<220>

<223> 小鼠U1a启动子序列

<400> 96

atggaggcgg tactatgtag atgagaattc aggagcaaac tgggaaaagc aactgcttcc 60

aaatatttgt gatttttaca gtgtagtttt ggaaaaactc ttagcctacc aattcttcta 120

agtgttttaa aatgtgggag ccagtacaca tgaagttata gagtgtttta atgaggctta 180

aatatttacc gtaactatga aatgctacgc atatcatgct gttcaggctc cgtggccacg 240

caactcatac 250

<210> 97

<211> 101

<212> DNA

<213> 人工序列

<220>

<223> 聚合酶III H1突变启动子序列

<400> 97

aatatttgca tgtcgctatg tgttctggga aatcaccata aacgtgaaat gtctttggat 60

ttgggaatct tcgaagttct gtatgagacc acagatctcc a 101

<210> 98

<211> 2214

<212> DNA

<213> 人工序列

<220>

<223> AAV110 DNA

<400> 98

atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60

gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120

gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180

aagggggagc ccgtcaacgc ggcggatgca gcggccctcg agcacgacaa ggcctacgac 240

cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300

caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360

gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420

ggaaagaaga gaccggtaga gccatcaccc cagcgttctc cagactcctc tacgggcatc 480

ggcaagaaag gccaacagcc cgccagaaaa agactcaatt ttggtcagac tggcgactca 540

gagtcagtcc ccgacccaca acctctcgga gaacctccag caacccccgc tgctgtggga 600

cctactacaa tggcttcagg cggtggcgca ccaatggcag acaataacga aggcgccgac 660

ggagtgggta atgcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720

atcaccacca gcacccgaac atgggccttg cccacctata acaaccacct ctacaagcaa 780

atctccagtg cttcaacggg ggccagcaac gacaaccact acttcggcta cagcaccccc 840

tgggggtatt ttgatttcaa cagattccac tgccatttct caccacgtga ctggcagcga 900

ctcatcaaca acaattgggg attccggccc aagagactca acttcaagct cttcaacatc 960

caagtcaagg aggtcacgac gaatgatggc gtcacgacca tcgctaataa ccttaccagc 1020

acggttcaag tcttctcgga ctcggagtac cagttgccgt acgtcctcgg ctctgcgcac 1080

cagggctgcc tccctccgtt cccggcggac gtgttcatga ttccgcagta cggctaccta 1140

acgctcaaca atggcagcca ggcagtggga cggtcatcct tttactgcct ggaatatttc 1200

ccatcgcaga tgctgagaac gggcaataac tttaccttca gctacacctt cgaggacgtg 1260

cctttccaca gcagctacgc gcacagccag agcctggacc ggctgatgaa tcctctcatc 1320

gaccagtacc tgtattacct gaacagaact cagaatcagt ccggaagtgc ccaaaacaag 1380

gacttgctgt ttagccgggg gtctccagct ggcatgtctg ttcagcccaa aaactggcta 1440

cctggaccct gttaccggca gcagcgcgtt tctaaaacaa aaacagacaa caacaacagc 1500

aactttacct ggactggtgc ttcaaaatat aaccttaatg ggcgtgaatc tataatcaac 1560

cctggcactg ctatggcctc acacaaagac gacaaagaca agttctttcc catgagcggt 1620

gtcatgattt ttggaaagga gagcgccgga gcttcaaaca ctgcattgga caatgtcatg 1680

atcacagacg aagaggaaat caaagccact aaccccgtgg ccaccgaaag atttgggact 1740

gtggcagtca atctccagag cagcagcaca gaccctgcga ccggagatgt gcatgttatg 1800

ggagccttac ctggaatggt gtggcaagac agagacgtat acctgcaggg tcctatttgg 1860

gccaaaattc ctcacacgga tggacacttt cacccgtctc ctctcatggg cggctttgga 1920

cttaagcacc cgcctcctca gatcctcatc aaaaacacgc ctgttcctgc gaatcctccg 1980

gcagagtttt cggctacaaa gtttgcttca ttcatcaccc agtattccac aggacaagtg 2040

agcgtggaga ttgaatggga gctgcagaaa gaaaacagca aacgctggaa tcccgaagtg 2100

cagtatacat ctaactatgc aaaatctgcc aacgttgatt tcactgtgga caacaatgga 2160

ctttatactg agcctcgccc cattggcacc cgttacctca cccgtcccct gtaa 2214

<210> 99

<211> 1509

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(1509)

<223> 磺基葡糖胺磺基水解酶 (SGSH)

<400> 99

atgagctgcc ccgtgcccgc ctgctgcgcg ctgctgctag tcctggggct ctgccgggcg 60

cgtccccgga acgcactgct gctcctcgcg gatgacggag gctttgagag tggcgcgtac 120

aacaacagcg ccatcgccac cccgcacctg gacgccttgg cccgccgcag cctcctcttt 180

cgcaatgcct tcacctcggt cagcagctgc tctcccagcc gcgccagcct cctcactggc 240

ctgccccagc atcagaatgg gatgtacggg ctgcaccagg acgtgcacca cttcaactcc 300

ttcgacaagg tgcggagcct gccgctgctg ctcagccaag ctggtgtgcg cacaggcatc 360

atcgggaaga agcacgtggg gccggagacc gtgtacccgt ttgactttgc gtacacggag 420

gagaatggct ccgtcctcca ggtggggcgg aacatcacta gaattaagct gctcgtccgg 480

aaattcctgc agactcagga tgaccagcct ttcttcctct acgtcgcctt ccacgacccc 540

caccgctgtg ggcactccca gccccagtac ggaaccttct gtgagaagtt tggcaacgga 600

gagagcggca tgggtcgtat cccagactgg accccccagg cctacgaccc actggacgtg 660

ctggtgcctt acttcgtccc caacaccccg gcagcccgag ccgacctggc cgctcagtac 720

accaccgtcg gccgcatgga ccaaggagtt ggactggtgc tccaggagct gcgtgacgcc 780

ggtgtcctga acgacacact ggtgatcttc acgtccgaca acgggatccc cttccccagc 840

ggcaggacca acctgtactg gccgggcact gctgaaccct tactggtgtc atccccggag 900

cacccaaaac gctggggcca agtcagcgag gcctacgtga gcctcctaga cctcacgccc 960

accatcttgg attggttctc gatcccgtac cccagctacg ccatctttgg ctcgaagacc 1020

atccacctca ctggccggtc cctcctgccg gcgctggagg ccgagcccct ctgggccacc 1080

gtctttggca gccagagcca ccacgaggtc accatgtcct accccatgcg ctccgtgcag 1140

caccggcact tccgcctcgt gcacaacctc aacttcaaga tgccctttcc catcgaccag 1200

gacttctacg tctcacccac cttccaggac ctcctgaacc gcaccacagc tggtcagccc 1260

acgggctggt acaaggacct ccgtcattac tactaccggg cgcgctggga gctctacgac 1320

cggagccggg acccccacga gacccagaac ctggccaccg acccgcgctt tgctcagctt 1380

ctggagatgc ttcgggacca gctggccaag tggcagtggg agacccacga cccctgggtg 1440

tgcgcccccg acggcgtcct ggaggagaag ctctctcccc agtgccagcc cctccacaat 1500

gagctgtga 1509

<210> 100

<211> 1509

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO1-SGSH

<400> 100

atgagctgtc ctgttccagc ctgttgtgcc ctgctgctgg ttctgggact gtgcagagcc 60

agacctagga acgctctgct gctgctcgct gacgatggcg gatttgagag cggcgcctac 120

aacaacagcg ccattgccac acctcacctg gatgccctgg ccagaagaag cctgctgttc 180

agaaacgcct tcaccagcgt gtccagctgc agcccttcta gagctagcct gctgacagga 240

ctgccccagc accagaatgg gatgtatggc ctgcaccagg acgtgcacca cttcaacagc 300

ttcgacaaag tgcggagcct gcctctgctt ctgtctcaag ccggcgtcag aacaggcatc 360

atcggcaaga aacacgtggg ccccgagaca gtgtacccct tcgatttcgc ctacaccgaa 420

gagaacggca gcgtgctgca agtgggcaga aacatcaccc ggatcaagct gctcgtgcgg 480

aagttcctgc agacccagga cgaccagcct ttcttcctgt acgtggcctt ccacgatcct 540

cacagatgcg gccatagcca gcctcagtac ggcaccttct gcgagaagtt tggcaacggc 600

gagagcggca tgggcagaat ccctgattgg acccctcagg cctacgatcc cctggatgtg 660

ctggtgcctt acttcgtgcc taacacacca gccgccagag ccgatctggc cgctcagtat 720

acaaccgtgg gaagaatgga ccaaggcgtc ggcctggttc tgcaagagct tagagatgcc 780

ggcgtgctga acgacaccct ggtcatcttt accagcgaca acggcatccc ctttccatct 840

ggccggacca atctgtactg gcctggaaca gctgagcccc tgctggtgtc tagccctgag 900

caccctaaga gatggggcca agtgtctgag gcctacgtgt ccctgctgga tctgacccct 960

accatcctgg actggttcag catcccctat cctagctacg ccatcttcgg cagcaagacc 1020

atccacctga ccggcagatc tctgctgcca gctctggaag ctgaacctct gtgggccaca 1080

gtgtttggca gccagtctca ccacgaagtg acaatgagct accccatgcg gagcgtgcag 1140

cacagacact tcagactggt gcacaacctg aacttcaaga tgccctttcc aatcgaccag 1200

gacttctatg tgtccccaac cttccaggac ctgctgaaca gaaccacagc cggccaacct 1260

accggctggt acaaggacct gcggcactac tactatagag ccagatggga gctgtacgac 1320

cggtccagag atccccacga gacacagaac ctggccaccg atcctagatt cgcccagctg 1380

ctggaaatgc tgagagatca gctggccaag tggcagtggg agacacacga tccttgggtc 1440

tgcgctcctg atggcgtgct ggaagagaag ctgtcccctc agtgtcagcc cctgcacaac 1500

gagctttaa 1509

<210> 101

<211> 1596

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的+ GET CO1-SGSH-GET

<400> 101

atgagctgtc ctgttccagc ctgttgtgcc ctgctgctgg ttctgggact gtgcagagcc 60

agacctagga acgctctgct gctgctcgct gacgatggcg gatttgagag cggcgcctac 120

aacaacagcg ccattgccac acctcacctg gatgccctgg ccagaagaag cctgctgttc 180

agaaacgcct tcaccagcgt gtccagctgc agcccttcta gagctagcct gctgacagga 240

ctgccccagc accagaatgg gatgtatggc ctgcaccagg acgtgcacca cttcaacagc 300

ttcgacaaag tgcggagcct gcctctgctt ctgtctcaag ccggcgtcag aacaggcatc 360

atcggcaaga aacacgtggg ccccgagaca gtgtacccct tcgatttcgc ctacaccgaa 420

gagaacggca gcgtgctgca agtgggcaga aacatcaccc ggatcaagct gctcgtgcgg 480

aagttcctgc agacccagga cgaccagcct ttcttcctgt acgtggcctt ccacgatcct 540

cacagatgcg gccatagcca gcctcagtac ggcaccttct gcgagaagtt tggcaacggc 600

gagagcggca tgggcagaat ccctgattgg acccctcagg cctacgatcc cctggatgtg 660

ctggtgcctt acttcgtgcc taacacacca gccgccagag ccgatctggc cgctcagtat 720

acaaccgtgg gaagaatgga ccaaggcgtc ggcctggttc tgcaagagct tagagatgcc 780

ggcgtgctga acgacaccct ggtcatcttt accagcgaca acggcatccc ctttccatct 840

ggccggacca atctgtactg gcctggaaca gctgagcccc tgctggtgtc tagccctgag 900

caccctaaga gatggggcca agtgtctgag gcctacgtgt ccctgctgga tctgacccct 960

accatcctgg actggttcag catcccctat cctagctacg ccatcttcgg cagcaagacc 1020

atccacctga ccggcagatc tctgctgcca gctctggaag ctgaacctct gtgggccaca 1080

gtgtttggca gccagtctca ccacgaagtg acaatgagct accccatgcg gagcgtgcag 1140

cacagacact tcagactggt gcacaacctg aacttcaaga tgccctttcc aatcgaccag 1200

gacttctatg tgtccccaac cttccaggac ctgctgaaca gaaccacagc cggccaacct 1260

accggctggt acaaggacct gcggcactac tactatagag ccagatggga gctgtacgac 1320

cggtccagag atccccacga gacacagaac ctggccaccg atcctagatt cgcccagctg 1380

ctggaaatgc tgagagatca gctggccaag tggcagtggg agacacacga tccttgggtc 1440

tgcgctcctg atggcgtgct ggaagagaag ctgtcccctc agtgtcagcc cctgcacaac 1500

gagctgcggc gtcgtcggcg aagaagaaga aagcgcaaga aaaaaggcaa aggcctgggc 1560

aagaagcggg acccctgtct gagaaagtac aaataa 1596

<210> 102

<211> 1509

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO2-SGSH

<400> 102

atgagctgcc ctgtgcctgc ctgctgtgcc ctgctgctgg tgctgggcct gtgcagagcc 60

agacctagga atgccctgct gctgctggct gatgatgggg gctttgagag tggggcctac 120

aacaacagtg ccattgccac cccccacctg gatgccctgg ccagaagaag cctgctgttc 180

agaaatgcct tcaccagtgt gagcagctgc agccccagca gagccagcct gctgacaggc 240

ctgccccagc accagaatgg catgtatggc ctgcaccagg atgtgcacca cttcaacagc 300

tttgacaagg tgagaagcct gcccctgctg ctgagccagg ctggggtgag aacaggcatc 360

attggcaaga agcatgtggg ccctgagaca gtgtacccct ttgactttgc ctacacagag 420

gagaatggca gtgtgctgca ggtgggcaga aacatcacca gaatcaagct gctggtgaga 480

aagttcctgc agacccagga tgaccagccc ttcttcctgt atgtggcctt ccatgacccc 540

cacagatgtg gccacagcca gccccagtat ggcaccttct gtgagaagtt tggcaatggg 600

gagagtggca tgggcagaat ccctgactgg accccccagg cctatgaccc cctggatgtg 660

ctggtgccct actttgtgcc caacacccct gctgccagag ctgacctggc tgcccagtac 720

accacagtgg gcagaatgga ccagggggtg ggcctggtgc tgcaggagct gagagatgct 780

ggggtgctga atgacaccct ggtgatcttc accagtgaca atggcatccc cttccccagt 840

ggcagaacca acctgtactg gcctggcaca gctgagcccc tgctggtgag cagccctgag 900

caccccaaga gatggggcca ggtgagtgag gcctatgtga gcctgctgga cctgaccccc 960

accatcctgg actggttcag catcccctac cccagctatg ccatctttgg cagcaagacc 1020

atccacctga caggcagaag cctgctgcct gccctggagg ctgagcccct gtgggccaca 1080

gtgtttggca gccagagcca ccatgaggtg accatgagct accccatgag aagtgtgcag 1140

cacagacact tcagactggt gcacaacctg aacttcaaga tgcccttccc cattgaccag 1200

gacttctatg tgagccccac cttccaggac ctgctgaaca gaaccacagc tggccagccc 1260

acaggctggt acaaggacct gagacactac tactacagag ccagatggga gctgtatgac 1320

agaagcagag acccccatga gacccagaac ctggccacag accccagatt tgcccagctg 1380

ctggagatgc tgagagacca gctggccaag tggcagtggg agacccatga cccctgggtg 1440

tgtgcccctg atggggtgct ggaggagaag ctgagccccc agtgccagcc cctgcacaat 1500

gagctgtga 1509

<210> 103

<211> 921

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的蜡样质脂褐质沉积症神经元蛋白1 (CLN1)

<400> 103

atggcttctc cggggtgtct gtggctgctg gcagtggcac tccttccctg gacttgcgcc 60

agccgggctc tgcagcacct cgaccctcca gcccctcttc cactggtgat ttggcacgga 120

atgggtgatt cctgctgtaa tcccctgtca atgggagcca tcaagaagat ggtggagaag 180

aagatccctg gaatctacgt gctgtcactg gagattggaa agaccctgat ggaggacgtc 240

gagaactcct tcttcctcaa tgtcaactct caagtgacca ccgtctgcca ggccctggcc 300

aaggacccga agctgcagca ggggtataat gctatggggt tcagccaggg aggacagttc 360

cttcgggctg tggcccaacg ctgccctagc ccacccatga tcaacctgat ctcagtgggt 420

ggccagcatc agggcgtgtt cggacttccc cggtgtcccg gggaatcctc tcatatctgc 480

gacttcatcc gcaaaactct caatgcaggc gcttattcaa aggtcgtcca agagaggctg 540

gtgcaagccg agtactggca cgatcccatt aaggaggacg tgtacagaaa tcactcaatc 600

tttctggccg acattaacca ggagagggga attaacgaat catataagaa gaatctcatg 660

gccctcaaaa agttcgtcat ggtgaagttc cttaacgata gcattgtgga cccagtggac 720

agcgaatggt tcggatttta ccgctcaggc caggcaaaag aaaccatccc tctccaagag 780

acttctcttt acacccaaga cagacttggg cttaaggaaa tggataacgc tggtcagctg 840

gtgttcctcg ccaccgaagg tgaccatctg cagctcagcg aagagtggtt ctacgctcat 900

atcatcccgt ttcttggttg a 921

<210> 104

<211> 885

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(885)

<223> 运动神经元生存蛋白1 (SMN1)

<400> 104

atggcgatga gcagcggcgg cagtggtggc ggcgtcccgg agcaggagga ttccgtgctg 60

ttccggcgcg gcacaggcca gagcgatgat tctgacattt gggatgatac agcactgata 120

aaagcatatg ataaagctgt ggcttcattt aagcatgctc taaagaatgg tgacatttgt 180

gaaacttcgg gtaaaccaaa aaccacacct aaaagaaaac ctgctaagaa gaataaaagc 240

caaaagaaga atactgcagc ttccttacaa cagtggaaag ttggggacaa atgttctgcc 300

atttggtcag aagacggttg catttaccca gctaccattg cttcaattga ttttaagaga 360

gaaacctgtg ttgtggttta cactggatat ggaaatagag aggagcaaaa tctgtccgat 420

ctactttccc caatctgtga agtagctaat aatatagaac agaatgctca agagaatgaa 480

aatgaaagcc aagtttcaac agatgaaagt gagaactcca ggtctcctgg aaataaatca 540

gataacatca agcccaaatc tgctccatgg aactcttttc tccctccacc accccccatg 600

ccagggccaa gactgggacc aggaaagcca ggtctaaaat tcaatggccc accaccgcca 660

ccgccaccac caccacccca cttactatca tgctggctgc ctccatttcc ttctggacca 720

ccaataattc ccccaccacc tcccatatgt ccagattctc ttgatgatgc tgatgctttg 780

ggaagtatgt taatttcatg gtacatgagt ggctatcata ctggctatta tatgggtttt 840

agacaaaatc aaaaagaagg aaggtgctca cattccttaa attaa 885

<210> 105

<211> 885

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO1-SMN1

<400> 105

atggcgatgt ctagtggtgg atctggtggc ggcgtgcccg agcaagaaga tagcgtcctg 60

ttcagaagag gcaccggcca gagcgacgac agcgacatct gggatgatac agccctgatc 120

aaggcctacg acaaggccgt ggccagcttt aagcacgccc tgaagaacgg cgatatctgc 180

gagacaagcg gcaagcccaa gaccacacct aagagaaagc ccgccaagaa gaacaagagc 240

cagaagaaga ataccgccgc cagcctgcag cagtggaaag tgggcgataa gtgcagcgcc 300

atttggagcg aggacggctg tatctaccct gccacaatcg ccagcatcga cttcaagcgg 360

gaaacctgcg tggtggtgta cacaggctac ggcaacagag aggaacagaa cctgagcgac 420

ctgctgtccc caatttgcga ggtggccaac aacatcgagc agaacgccca agagaacgag 480

aacgagtccc aggtgtccac cgacgagagc gagaatagca gaagccccgg caacaagagc 540

gacaacatca agcctaagag cgccccttgg aacagcttcc tgcctcctcc tccaccaatg 600

cctggaccta gactcggacc tggaaagccc ggcctgaagt tcaatggacc tccaccaccg 660

ccaccacctc cgcctccaca tcttctgtct tgttggctgc ctccatttcc tagcggccct 720

ccaatcatcc cgccacctcc acctatctgc cccgacagtc tggatgatgc tgatgccctg 780

ggctccatgc tgatctcttg gtacatgagc ggctaccaca ccggctacta catgggcttc 840

agacagaacc agaaagaggg ccgttgcagc cacagcctga actga 885

<210> 106

<211> 885

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO2-SMN1

<400> 106

atggccatga gcagtggggg cagtggagga ggggtgcctg agcaggagga cagtgtgctg 60

ttcagaagag gcacaggcca gagtgatgac agtgacatct gggatgacac agccctgatc 120

aaggcctatg acaaggctgt ggccagcttc aagcatgccc tgaagaatgg ggacatctgt 180

gagaccagtg gcaagcccaa gaccaccccc aagagaaagc ctgccaagaa gaacaagagc 240

cagaagaaga acacagctgc cagcctgcag cagtggaagg tgggagacaa gtgcagtgcc 300

atctggagtg aggatggctg catctaccct gccaccattg ccagcattga cttcaagaga 360

gagacctgtg tggtggtgta cacaggctat ggcaacagag aggagcagaa cctgagtgac 420

ctgctgagcc ccatctgtga ggtggccaac aacattgagc agaatgccca ggagaatgag 480

aatgagagcc aggtgagcac agatgagagt gagaacagca gaagccctgg caacaagagt 540

gacaacatca agcccaagag tgccccttgg aacagcttcc tgccaccccc accacccatg 600

cctggcccca gactgggccc tggcaagcct ggcctgaagt tcaatggccc accaccccct 660

cctccaccac cccctcccca cctgctgagc tgctggctgc cccccttccc cagtggccca 720

cccatcatcc cacctccccc acccatctgc cctgacagcc tggatgatgc tgatgccctg 780

ggcagcatgc tgatcagctg gtacatgagt ggctaccaca caggctacta catgggcttc 840

agacagaacc agaaggaggg cagatgcagc cacagcctga actga 885

<210> 107

<211> 1548

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(1548)

<223> 组织非特异性碱性磷酸酶 (TNALP)

<400> 107

atgatttcac cattcttagt actggccatt ggcacctgcc ttactaactc actagtgcca 60

gagaaagaga aagaccccaa gtactggcga gaccaagcgc aagagacact gaaatatgcc 120

ctggagcttc agaagctcaa caccaacgtg gctaagaatg tcatcatgtt cctgggagat 180

gggatgggtg tctccacagt gacggctgcc cgcatcctca agggtcagct ccaccacaac 240

cctggggagg agaccaggct ggagatggac aagttcccct tcgtggccct ctccaagacg 300

tacaacacca atgcccaggt ccctgacagc gccggcaccg ccaccgccta cctgtgtggg 360

gtgaaggcca atgagggcac cgtgggggta agcgcagcca ctgagcgttc ccggtgcaac 420

accacccagg ggaacgaggt cacctccatc ctgcgctggg ccaaggacgc tgggaaatct 480

gtgggcattg tgaccaccac gagagtgaac catgccaccc ccagcgccgc ctacgcccac 540

tcggctgacc gggactggta ctcagacaac gagatgcccc ctgaggcctt gagccagggc 600

tgtaaggaca tcgcctacca gctcatgcat aacatcaggg acattgacgt gatcatgggg 660

ggtggccgga aatacatgta ccccaagaat aaaactgatg tggagtatga gagtgacgag 720

aaagccaggg gcacgaggct ggacggcctg gacctcgttg acacctggaa gagcttcaaa 780

ccgagataca agcactccca cttcatctgg aaccgcacgg aactcctgac ccttgacccc 840

cacaatgtgg actacctatt gggtctcttc gagccagggg acatgcagta cgagctgaac 900

aggaacaacg tgacggaccc gtcactctcc gagatggtgg tggtggccat ccagatcctg 960

cggaagaacc ccaaaggctt cttcttgctg gtggaaggag gcagaattga ccacgggcac 1020

catgaaggaa aagccaagca ggccctgcat gaggcggtgg agatggaccg ggccatcggg 1080

caggcaggca gcttgacctc ctcggaagac actctgaccg tggtcactgc ggaccattcc 1140

cacgtcttca catttggtgg atacaccccc cgtggcaact ctatctttgg tctggccccc 1200

atgctgagtg acacagacaa gaagcccttc actgccatcc tgtatggcaa tgggcctggc 1260

tacaaggtgg tgggcggtga acgagagaat gtctccatgg tggactatgc tcacaacaac 1320

taccaggcgc agtctgctgt gcccctgcgc cacgagaccc acggcgggga ggacgtggcc 1380

gtcttctcca agggccccat ggcgcacctg ctgcacggcg tccacgagca gaactacgtc 1440

ccccacgtga tggcgtatgc agcctgcatc ggggccaacc tcggccactg tgctcctgcc 1500

agctcggcag gatccgatga tgacgacgac gatgacgatg atgattga 1548

<210> 108

<211> 1548

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的，CO1-TNALP在C端含有D10标签

<400> 108

atgatctctc catttctggt gctggccatc ggcacctgtc tgaccaactc actagtgccc 60

gagaaagaga aggaccccaa gtactggcgc gatcaggccc aagagacact gaagtacgcc 120

ctggaactgc agaaactgaa caccaacgtg gccaagaacg tgatcatgtt cctcggcgac 180

ggcatgggcg tgtccacagt tacagccgcc agaatcctga agggccagct gcaccataat 240

cctggcgaag agacacggct ggaaatggac aagttcccat tcgtggccct gagcaagacc 300

tacaacacca atgctcaggt gcccgattct gccggaacag ccacagctta tctgtgcggc 360

gtgaaggcca atgagggcac cgttggagtg tctgccgcca ccgaaagatc ccggtgcaat 420

accacacagg gcaacgaagt gaccagcatc ctgagatggg ccaaagacgc cggcaagtct 480

gtgggcatcg tgaccaccac cagagtgaac cacgccacac ctagcgccgc ctatgctcac 540

tctgccgaca gagactggta cagcgacaac gagatgcctc ctgaggctct gtctcagggc 600

tgcaaggata tcgcctacca gctgatgcac aacatccggg acattgatgt gatcatgggc 660

ggaggccgga agtacatgta tcccaagaac aagaccgacg tcgagtacga gagcgacgag 720

aaggccagag gcacaagact ggatggcctg gacctggtgg atacctggaa gtccttcaag 780

ccccggtaca agcacagcca cttcatctgg aaccggaccg agctgctgac actggaccct 840

cacaatgtgg actacctgct gggcctgttc gagcccggcg atatgcagta cgagctgaac 900

cggaacaacg tgacagaccc cagcctgagc gagatggtgg ttgtggccat tcagatcctg 960

cggaagaacc ccaagggatt cttcctgctg gtggaaggcg gcaggatcga tcacggacac 1020

catgagggaa aagccaagca ggccctgcac gaggccgtcg aaatggatag agccattggc 1080

caggccggca gcctgacaag ctctgaggat acactgaccg tggtcaccgc cgatcacagc 1140

cacgtgttca cattcggcgg ctacacccct agaggcaaca gcatctttgg actggcccct 1200

atgctgagcg acaccgacaa gaagcctttc accgccatcc tgtacggcaa cggccctggc 1260

tataaggttg tcggaggcga gagggaaaac gtgtccatgg tggattacgc ccacaacaac 1320

taccaggctc agagcgccgt gcctctgaga cacgaaacac acggcggaga agatgtggcc 1380

gtgttcagca agggccccat ggctcatctg ctgcatggcg tgcacgagca gaattacgtg 1440

ccacacgtga tggcctacgc cgcctgtatt ggagccaatc tgggacattg tgcccctgcc 1500

agtagcgccg gatccgacga tgatgacgac gacgatgacg atgactga 1548

<210> 109

<211> 1548

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的，CO2-TNALP在C端含有D10标签

<400> 109

atgatcagcc ccttcctggt gctggccatt ggcacctgcc tgaccaacag cctggtgcct 60

gagaaggaga aggaccccaa gtactggaga gaccaggccc aggagaccct gaagtatgcc 120

ctggagctgc agaagctgaa caccaatgtg gccaagaatg tgatcatgtt cctgggggat 180

ggcatggggg tgagcacagt gacagctgcc agaatcctga agggccagct gcaccacaac 240

cctggggagg agaccagact ggagatggac aagttcccct ttgtggccct gagcaagacc 300

tacaacacca atgcccaggt gcctgacagt gctggcacag ccacagccta cctgtgtggg 360

gtgaaggcca atgagggcac agtgggggtg agtgctgcca cagagagaag cagatgcaac 420

accacccagg gcaatgaggt gaccagcatc ctgagatggg ccaaggatgc tggcaagagt 480

gtgggcattg tgaccaccac cagagtgaac catgccaccc ccagtgctgc ctatgcccac 540

agtgctgaca gagactggta cagtgacaat gagatgcccc ctgaggccct gagccagggc 600

tgcaaggaca ttgcctacca gctgatgcac aacatcagag acattgatgt gatcatgggg 660

gggggcagaa agtacatgta ccccaagaac aagacagatg tggagtatga gagtgatgag 720

aaggccagag gcaccagact ggatggcctg gacctggtgg acacctggaa gagcttcaag 780

cccagataca agcacagcca cttcatctgg aacagaacag agctgctgac cctggacccc 840

cacaatgtgg actacctgct gggcctgttt gagcctgggg acatgcagta tgagctgaac 900

agaaacaatg tgacagaccc cagcctgagt gagatggtgg tggtggccat ccagatcctg 960

agaaagaacc ccaagggctt cttcctgctg gtggaggggg gcagaattga ccatggccac 1020

catgagggca aggccaagca ggccctgcat gaggctgtgg agatggacag agccattggc 1080

caggctggca gcctgaccag cagtgaggac accctgacag tggtgacagc tgaccacagc 1140

catgtgttca cctttggggg ctacaccccc agaggcaaca gcatctttgg cctggccccc 1200

atgctgagtg acacagacaa gaagcccttc acagccatcc tgtatggcaa tggccctggc 1260

tacaaggtgg tgggggggga gagagagaat gtgagcatgg tggactatgc ccacaacaac 1320

taccaggccc agagtgctgt gcccctgaga catgagaccc atggggggga ggatgtggct 1380

gtgttcagca agggccccat ggcccacctg ctgcatgggg tgcatgagca gaactatgtg 1440

ccccatgtga tggcctatgc tgcctgcatt ggggccaacc tgggccactg tgcccctgcc 1500

agcagtgctg gatccgatga tgatgatgat gatgatgatg atgactga 1548

<210> 110

<211> 636

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(636)

<223> 神经胶质细胞源性神经营养因子 (GDNF)

<400> 110

atgaagttat gggatgtcgt ggctgtctgc ctggtgctgc tccacaccgc gtccgccttc 60

ccgctgcccg ccggcaagag gcctcccgag gcgcccgccg aagaccgctc cctcggccgc 120

cgccgcgcgc ccttcgcgct gagcagtgac tcaaatatgc cagaggatta tcctgatcag 180

ttcgatgatg tcatggattt tattcaagcc accattaaaa gactgaaaag gtcaccagat 240

aaacaaatgg cagtgcttcc tagaagagag cggaatcggc aggctgcagc tgccaaccca 300

gagaattcca gaggaaaagg tcggagaggc cagaggggca aaaaccgggg ttgtgtctta 360

actgcaatac atttaaatgt cactgacttg ggtctgggct atgaaaccaa ggaggaactg 420

atttttaggt actgcagcgg ctcttgcgat gcagctgaga caacgtacga caaaatattg 480

aaaaacttat ccagaaatag aaggctggtg agtgacaaag tagggcaggc atgttgcaga 540

cccatcgcct ttgatgatga cctgtcgttt ttagatgata acctggttta ccatattcta 600

agaaagcatt ccgctaaaag gtgtggatgt atctaa 636

<210> 111

<211> 1611

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(1611)

<223> 组织葡糖基神经酰胺酶β (GBA1)

<400> 111

atggagtttt caagtccttc cagagaggaa tgtcccaagc ctttgagtag ggtaagcatc 60

atggctggca gcctcacagg attgcttcta cttcaggcag tgtcgtgggc atcaggtgcc 120

cgcccctgca tccctaaaag cttcggctac agctcggtgg tgtgtgtctg caatgccaca 180

tactgtgact cctttgaccc cccgaccttt cctgcccttg gtaccttcag ccgctatgag 240

agtacacgca gtgggcgacg gatggagctg agtatggggc ccatccaggc taatcacacg 300

ggcacaggcc tgctactgac cctgcagcca gaacagaagt tccagaaagt gaagggattt 360

ggaggggcca tgacagatgc tgctgctctc aacatccttg ccctgtcacc ccctgcccaa 420

aatttgctac ttaaatcgta cttctctgaa gaaggaatcg gatataacat catccgggta 480

ccaatggcca gctgtgactt ctccatccgc acctacacct atgcagacac ccctgatgat 540

ttccagttgc acaacttcag cctcccagag gaagatacca agctcaagat acccctgatt 600

caccgagccc tgcagttggc ccagcgtccc gtttcactcc ttgccagccc ctggacatca 660

cccacttggc tcaagaccaa tggagcggtg aatgggaagg ggtcactcaa gggacagccc 720

ggagacatct accaccagac ctgggccaga tactttgtga agttcctgga tgcctatgct 780

gagcacaagt tacagttctg ggcagtgaca gctgaaaatg agccttctgc tgggctgttg 840

agtggatacc ccttccagtg cctgggcttc acccctgaac atcagcgaga cttcattgcc 900

cgtgacctag gtcctaccct cgccaacagt actcaccaca atgtccgcct actcatgctg 960

gatgaccaac gcttgctgct gccccactgg gcaaaggtgg tactgacaga cccagaagca 1020

gctaaatatg ttcatggcat tgctgtacat tggtacctgg actttctggc tccagccaaa 1080

gccaccctag gggagacaca ccgcctgttc cccaacacca tgctctttgc ctcagaggcc 1140

tgtgtgggct ccaagttctg ggagcagagt gtgcggctag gctcctggga tcgagggatg 1200

cagtacagcc acagcatcat cacgaacctc ctgtaccatg tggtcggctg gaccgactgg 1260

aaccttgccc tgaaccccga aggaggaccc aattgggtgc gtaactttgt cgacagtccc 1320

atcattgtag acatcaccaa ggacacgttt tacaaacagc ccatgttcta ccaccttggc 1380

cacttcagca agttcattcc tgagggctcc cagagagtgg ggctggttgc cagtcagaag 1440

aacgacctgg acgcagtggc actgatgcat cccgatggct ctgctgttgt ggtcgtgcta 1500

aaccgctcct ctaaggatgt gcctcttacc atcaaggatc ctgctgtggg cttcctggag 1560

acaatctcac ctggctactc cattcacacc tacctgtggc gtcgccagtg a 1611

<210> 112

<211> 1611

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO1-GBA1

<400> 112

atggagttca gcagccccag cagagaggag tgccccaagc ccctgagcag agtgagcatc 60

atggctggca gcctgacagg cctgctgctg ctgcaggctg tgagctgggc cagtggggcc 120

agaccctgca tccccaagag ctttggctac agcagtgtgg tgtgtgtgtg caatgccacc 180

tactgtgaca gctttgaccc ccccaccttc cctgccctgg gcaccttcag cagatatgag 240

agcaccagaa gtggcagaag aatggagctg agcatgggcc ccatccaggc caaccacaca 300

ggcacaggcc tgctgctgac cctgcagcct gagcagaagt tccagaaggt gaagggcttt 360

gggggggcca tgacagatgc tgctgccctg aacatcctgg ccctgagccc ccctgcccag 420

aacctgctgc tgaagagcta cttcagtgag gagggcattg gctacaacat catcagagtg 480

ccaatggcca gctgtgactt cagcatcaga acctacacct atgctgacac ccctgatgac 540

ttccagctgc acaacttcag cctgcctgag gaggacacca agctgaagat ccccctgatc 600

cacagagccc tgcagctggc ccagagacct gtgagcctgc tggccagccc ctggaccagc 660

cccacctggc tgaagaccaa tggggctgtg aatggcaagg gcagcctgaa gggccagcct 720

ggggacatct accaccagac ctgggccaga tactttgtga agttcctgga tgcctatgct 780

gagcacaagc tgcagttctg ggctgtgaca gctgagaatg agcccagtgc tggcctgctg 840

agtggctacc ccttccagtg cctgggcttc acccctgagc accagagaga cttcattgcc 900

agagacctgg gccccaccct ggccaacagc acccaccaca atgtgagact gctgatgctg 960

gatgaccaga gactgctgct gccccactgg gccaaggtgg tgctgacaga ccctgaggct 1020

gccaagtatg tgcatggcat tgctgtgcac tggtacctgg acttcctggc ccctgccaag 1080

gccaccctgg gggagaccca cagactgttc cccaacacca tgctgtttgc cagtgaggcc 1140

tgtgtgggca gcaagttctg ggagcagagt gtgagactgg gcagctggga cagaggcatg 1200

cagtacagcc acagcatcat caccaacctg ctgtaccatg tggtgggctg gacagactgg 1260

aacctggccc tgaaccctga ggggggcccc aactgggtga gaaactttgt ggacagcccc 1320

atcattgtgg acatcaccaa ggacaccttc tacaagcagc ccatgttcta ccacctgggc 1380

cacttcagca agttcatccc tgagggcagc cagagagtgg gcctggtggc cagccagaag 1440

aatgacctgg atgctgtggc cctgatgcac cctgatggca gtgctgtggt ggtggtgctg 1500

aacagaagca gcaaggatgt gcccctgacc atcaaggacc ctgctgtggg cttcctggag 1560

accatcagcc ctggctacag catccacacc tacctgtgga gaagacagtg a 1611

<210> 113

<211> 1611

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO2-GBA1

<400> 113

atggagttta gcagccctag cagagaggaa tgccccaagc ctctgagccg ggtgtcaatc 60

atggccggat ctctgacagg actgctgctg cttcaggccg tgtcttgggc ttctggcgct 120

agaccttgca tccccaagag cttcggctac agcagcgtcg tgtgcgtgtg caatgccacc 180

tactgcgaca gcttcgaccc tcctaccttt cctgctctgg gcaccttcag cagatacgag 240

agcaccagat ccggcagacg gatggaactg agcatgggac ccatccaggc caatcacaca 300

ggcactggcc tgctgctgac actgcagcct gagcagaaat tccagaaagt gaaaggcttc 360

ggcggagcca tgacagatgc cgccgctctg aatatcctgg ctctgtctcc accagctcag 420

aacctgctgc tcaagagcta cttcagcgag gaaggcatcg gctacaacat catccgggtg 480

ccaatggcca gctgcgactt cagcatccgg acctacacct acgccgacac acccgacgat 540

ttccagctgc acaacttcag cctgcctgaa gaggacacca agctgaagat ccctctgatc 600

cacagagccc tgcagctggc acaaagaccc gtttctctgc tggctagccc ctggacatct 660

cccacctggc tgaaaacaaa tggcgccgtg aatggcaagg gcagcctgaa aggccaacct 720

ggcgatatct accaccagac ctgggccaga tacttcgtga agttcctgga cgcctatgcc 780

gagcacaagc tgcagttttg ggccgtgaca gccgagaacg aaccttctgc tggactgctg 840

agcggctacc cctttcagtg cctgggcttt acacccgagc accagcggga ctttatcgcc 900

agagatctgg gacccacact ggccaatagc acccaccata atgtgcggct gctgatgctg 960

gacgaccaga gactgcttct gccccactgg gctaaagtgg tgctgacaga tcctgaggcc 1020

gccaaatacg tgcacggaat cgccgtgcac tggtatctgg actttctggc ccctgccaag 1080

gccacactgg gagagacaca cagactgttc cccaacacca tgctgttcgc cagcgaagcc 1140

tgtgtgggca gcaagttttg ggaacagagc gtgcggctcg gcagctggga tagaggcatg 1200

cagtacagcc acagcatcat caccaacctg ctgtaccacg tcgtcggctg gaccgactgg 1260

aatctggccc tgaatcctga aggcggccct aactgggtcc gaaacttcgt ggacagcccc 1320

atcatcgtgg acatcaccaa ggacaccttc tacaagcagc ccatgttcta ccacctggga 1380

cacttcagca agttcatccc cgagggctct cagcgcgttg gactggtggc cagccagaag 1440

aatgatctgg acgccgtggc tctgatgcac cctgatggat ctgctgtggt ggtggtcctg 1500

aaccgcagca gcaaagatgt gcccctgacc atcaaggatc ccgccgtggg attcctggaa 1560

acaatcagcc ctggctactc catccacacc tacctgtggc ggagacagtg a 1611

<210> 114

<211> 1962

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(1962)

<223> 艾杜糖苷酸酶α-L- (IDUA)

<400> 114

atgcgtcccc tgcgcccccg cgccgcgctg ctggcgctcc tggcctcgct cctggccgcg 60

cccccggtgg ccccggccga ggccccgcac ctggtgcatg tggacgcggc ccgcgcgctg 120

tggcccctgc ggcgcttctg gaggagcaca ggcttctgcc ccccgctgcc acacagccag 180

gctgaccagt acgtcctcag ctgggaccag cagctcaacc tcgcctatgt gggcgccgtc 240

cctcaccgcg gcatcaagca ggtccggacc cactggctgc tggagcttgt caccaccagg 300

gggtccactg gacggggcct gagctacaac ttcacccacc tggacgggta cctggacctt 360

ctcagggaga accagctcct cccagggttt gagctgatgg gcagcgcctc gggccacttc 420

actgactttg aggacaagca gcaggtgttt gagtggaagg acttggtctc cagcctggcc 480

aggagataca tcggtaggta cggactggcg catgtttcca agtggaactt cgagacgtgg 540

aatgagccag accaccacga ctttgacaac gtctccatga ccatgcaagg cttcctgaac 600

tactacgatg cctgctcgga gggtctgcgc gccgccagcc ccgccctgcg gctgggaggc 660

cccggcgact ccttccacac cccaccgcga tccccgctga gctggggcct cctgcgccac 720

tgccacgacg gtaccaactt cttcactggg gaggcgggcg tgcggctgga ctacatctcc 780

ctccacagga agggtgcgcg cagctccatc tccatcctgg agcaggagaa ggtcgtcgcg 840

cagcagatcc ggcagctctt ccccaagttc gcggacaccc ccatttacaa cgacgaggcg 900

gacccgctgg tgggctggtc cctgccacag ccgtggaggg cggacgtgac ctacgcggcc 960

atggtggtga aggtcatcgc gcagcatcag aacctgctac tggccaacac cacctccgcc 1020

ttcccctacg cgctcctgag caacgacaat gccttcctga gctaccaccc gcaccccttc 1080

gcgcagcgca cgctcaccgc gcgcttccag gtcaacaaca cccgcccgcc gcacgtgcag 1140

ctgttgcgca agccggtgct cacggccatg gggctgctgg cgctgctgga tgaggagcag 1200

ctctgggccg aagtgtcgca ggccgggacc gtcctggaca gcaaccacac ggtgggcgtc 1260

ctggccagcg cccaccgccc ccagggcccg gccgacgcct ggcgcgccgc ggtgctgatc 1320

tacgcgagcg acgacacccg cgcccacccc aaccgcagcg tcgcggtgac cctgcggctg 1380

cgcggggtgc cccccggccc gggcctggtc tacgtcacgc gctacctgga caacgggctc 1440

tgcagccccg acggcgagtg gcggcgcctg ggccggcccg tcttccccac ggcagagcag 1500

ttccggcgca tgcgcgcggc tgaggacccg gtggccgcgg cgccccgccc cttacccgcc 1560

ggcggccgcc tgaccctgcg ccccgcgctg cggctgccgt cgcttttgct ggtgcacgtg 1620

tgtgcgcgcc ccgagaagcc gcccgggcag gtcacgcggc tccgcgccct gcccctgacc 1680

caagggcagc tggttctggt ctggtcggat gaacacgtgg gctccaagtg cctgtggaca 1740

tacgagatcc agttctctca ggacggtaag gcgtacaccc cggtcagcag gaagccatcg 1800

accttcaacc tctttgtgtt cagcccagac acaggtgctg tctctggctc ctaccgagtt 1860

cgagccctgg actactgggc ccgaccaggc cccttctcgg accctgtgcc gtacctggag 1920

gtccctgtgc caagagggcc cccatccccg ggcaatccat ga 1962

<210> 115

<211> 1962

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO1-IDUA

<400> 115

atgagacccc tgagacccag agctgccctg ctggccctgc tggccagcct gctggctgcc 60

ccccctgtgg cccctgctga ggccccccac cttgtacatg tggatgctgc cagagccctg 120

tggcccctga gaagattctg gagaagcaca ggcttctgcc cccccctgcc ccacagccag 180

gctgaccagt atgtgctgag ctgggaccag cagctgaacc tggcctatgt gggggctgtg 240

ccccacagag gcatcaagca ggtgagaacc cactggctgc tggagctggt gaccaccaga 300

ggcagcacag gcagaggcct gagctacaac ttcacccacc tggatggcta cctggacctg 360

ctgagagaga accagctgct gcctggcttt gagctgatgg gcagtgccag tggccacttc 420

acagactttg aggacaagca gcaggtgttt gagtggaagg acctggtgag cagcctggcc 480

agaagataca ttggcagata tggcctggcc catgtgagca agtggaactt tgagacctgg 540

aatgagcctg accaccatga ctttgacaat gtgagcatga ccatgcaggg cttcctgaac 600

tactatgatg cctgcagtga gggcctgaga gctgccagcc ctgccctgag actggggggc 660

cctggggaca gcttccacac cccccccaga agccccctga gctggggcct gctgagacac 720

tgccatgatg gcaccaactt cttcacaggg gaggctgggg tgagactgga ctacatcagc 780

ctgcacagaa agggggccag aagcagcatc agcatcctgg agcaggagaa ggtggtggcc 840

cagcagatca gacagctgtt ccccaagttt gctgacaccc ccatctacaa tgatgaggct 900

gaccccctgg tgggctggag cctgccccag ccctggagag ctgatgtgac ctatgctgcc 960

atggtggtga aggtgattgc ccagcaccag aacctgctgc tggccaacac caccagtgcc 1020

ttcccctatg ccctgctgag caatgacaat gccttcctga gctaccaccc ccaccccttt 1080

gcccagagaa ccctgacagc cagattccag gtgaacaaca ccagaccccc ccatgtgcag 1140

ctgctgagaa agcctgtgct gacagccatg ggcctgctgg ccctgctgga tgaggagcag 1200

ctgtgggctg aggtgagcca ggctggcaca gtgctggaca gcaaccacac agtgggggtg 1260

ctggccagtg cccacagacc ccagggccct gctgatgcct ggagagctgc tgtgctgatc 1320

tatgccagtg atgacaccag agcccacccc aacagaagtg tggctgtgac cctgagactg 1380

agaggggtgc cccctggccc tggcctggtg tatgtgacca gatacctgga caatggcctg 1440

tgcagccctg atggggagtg gagaagactg ggcagacctg tgttccccac agctgagcag 1500

ttcagaagaa tgagagctgc tgaggaccct gtggctgctg cccccagacc cctgcctgct 1560

gggggcagac tgaccctgag acctgccctg agactgccca gcctgctgct ggtgcatgtg 1620

tgtgccagac ctgagaagcc ccctggccag gtgaccagac tgagagccct gcccctgacc 1680

cagggccagc tggtgctggt gtggagtgat gagcatgtgg gcagcaagtg cctgtggacc 1740

tatgagatcc agttcagcca ggatggcaag gcctacaccc ctgtgagcag aaagcccagc 1800

accttcaacc tgtttgtgtt cagccctgac acaggggctg tgagtggcag ctacagagtg 1860

agagccctgg actactgggc cagacctggc cccttcagtg accctgtgcc ctacctggag 1920

gtgcctgtgc ccagaggccc ccccagccct ggcaacccct ga 1962

<210> 116

<211> 1578

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(1578)

<223> 细胞色素P450家族4亚家族V成员2 (CYP4V2)

<400> 116

atggcggggc tctggctggg gctcgtgtgg cagaagctgc tgctgtgggg cgcggcgagt 60

gccctttccc tggccggcgc cagtctggtc ctgagcctgc tgcagagggt ggcgagctac 120

gcgcggaaat ggcagcagat gcggcccatc cccacggtgg cccgcgccta cccactggtg 180

ggccacgcgc tgctgatgaa gccggacggg cgagaatttt ttcagcagat cattgagtac 240

acagaggaat accgccacat gccgctgctg aagctctggg tcgggccagt gcccatggtg 300

gccctttata atgcagaaaa tgtggaggta attttaacta gttcaaagca aattgacaaa 360

tcctctatgt acaagttttt agaaccatgg cttggcctag gacttcttac aagtactgga 420

aacaaatggc gctccaggag aaagatgtta acacccactt tccattttac cattctggaa 480

gatttcttag atatcatgaa tgaacaagca aatatattgg ttaagaaact tgaaaaacac 540

attaaccaag aagcatttaa ctgctttttt tacatcactc tttgtgcctt agatatcatc 600

tgtgaaacag ctatggggaa gaatattggt gctcaaagta atgatgattc cgagtatgtc 660

cgtgcagttt atagaatgag tgagatgata tttcgaagaa taaagatgcc ctggctttgg 720

cttgatctct ggtatcttat gtttaaagaa ggatgggaac acaaaaagag ccttcagatc 780

ctacatactt ttaccaacag tgtcatcgct gaacgggcca atgaaatgaa cgccaatgaa 840

gactgtagag gtgatggcag gggctctgcc ccctccaaaa ataaacgcag ggcctttctt 900

gacttgcttt taagtgtgac tgatgacgaa gggaacaggc taagtcatga agatattcga 960

gaagaagttg acaccttcat gtttgagggg cacgatacaa ctgcagctgc aataaactgg 1020

tccttatacc tgttgggttc taacccagaa gtccagaaaa aagtggatca tgaattggat 1080

gacgtgtttg ggaagtctga ccgtcccgct acagtagaag acctgaagaa acttcggtat 1140

ctggaatgtg ttattaagga gacccttcgc ctttttcctt ctgttccttt atttgcccgt 1200

agtgttagtg aagattgtga agtggcaggt tacagagttc taaaaggcac tgaagccgtc 1260

atcattccct atgcattgca cagagatccg agatacttcc ccaaccccga ggagttccag 1320

cctgagcggt tcttccccga gaatgcacaa gggcgccatc catatgccta cgtgcccttc 1380

tctgctggcc ccaggaactg tataggtcaa aagtttgctg tgatggaaga aaagaccatt 1440

ctttcgtgca tcctgaggca cttttggata gaatccaacc agaaaagaga agagcttggt 1500

ctagaaggac agttgattct tcgtccaagt aatggcatct ggatcaagtt gaagaggaga 1560

aatgcagatg aacgctaa 1578

<210> 117

<211> 711

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(711)

<223> 视网膜劈裂蛋白 1 (RS1)

<400> 117

atgagccgca agatagaagg ctttttgtta ttacttctct ttggctatga agccacattg 60

ggattatcgt ctaccgagga tgaaggcgag gacccctggt atcaaaaagc atgcgatgaa 120

ggcgaggacc cctggtatca aaaagcatgc aagtgcgatt gccaaggagg acccaatgct 180

ctgtggtctg caggtgccac ctccttggac tgtataccag aatgcccata tcacaagcct 240

ctgggtttcg agtcagggga ggtcacaccg gaccagatca cctgctctaa cccggagcag 300

tatgtgggct ggtattcttc gtggactgca aacaaggccc ggctcaacag tcaaggcttt 360

gggtgtgcct ggctctccaa gttccaggac agtagccagt ggttacagat agatctgaag 420

gagatcaaag tgatttcagg gatcctcacc caggggcgct gtgacatcga tgagtggatg 480

accaagtaca gcgtgcagta caggaccgat gagcgcctga actggattta ctacaaggac 540

cagactggaa acaaccgggt cttctatggc aactcggacc gcacctccac ggttcagaac 600

ctgctgcggc cccccatcat ctcccgcttc atccgcctca tcccgctggg ctggcacgtc 660

cgcattgcca tccggatgga gctgctggag tgcgtcagca agtgtgcctg a 711

<210> 118

<211> 2565

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(2565)

<223> 磷酸二酯酶 6B (PDE6B)

<400> 118

atgagcctca gtgaggagca ggcccggagc tttctggacc agaaccccga ttttgcccgc 60

cagtactttg ggaagaaact gagccctgag aatgtggccg cggcctgcga ggacgggtgc 120

ccgccggact gcgacagcct ccgggacctc tgccaggtgg aggagagcac ggcgctgctg 180

gagctggtgc aggatatgca ggagagcatc aacatggagc gcgtggtctt caaggtcctg 240

cggcgcctct gcaccctgct gcaggccgac cgctgcagcc tcttcatgta ccgccagcgc 300

aacggcgtgg ccgagctggc caccaggctt ttcagcgtgc agccggacag cgtcctggag 360

gactgcctgg tgccccccga ctccgagatc gtcttcccac tggacatcgg ggtcgtgggc 420

cacgtggctc agaccaaaaa gatggtgaac gtcgaggacg tggccgagtg ccctcacttc 480

agctcatttg ctgacgagct cactgactac aagacaaaga atatgctggc cacacccatc 540

atgaatggca aagacgtcgt ggcggtgatc atggcagtga acaagctcaa cggcccattc 600

ttcaccagcg aagacgaaga tgtgttcttg aagtacctga attttgccac gttgtacctg 660

aaaatctatc acctgagcta cctccacaac tgcgagacgc gccgcggcca ggtgctgctg 720

tggtcggcca acaaggtgtt tgaggagctg acggacatcg agaggcagtt ccacaaggcc 780

ttctacacgg tgcgggccta cctcaactgc gagcggtact ccgtgggcct cctggacatg 840

accaaggaga aggaattttt tgacgtgtgg tctgtgctga tgggagagtc ccagccgtac 900

tcgggcccac gcacgcctga tggccgggaa attgtcttct acaaagtgat cgactacatc 960

ctccacggca aggaggagat caaggtcatt cccacaccct cagccgatca ctgggccctg 1020

gccagcggcc ttccaagcta cgtggcagaa agcggcttta tttgtaacat catgaatgct 1080

tccgctgacg aaatgttcaa atttcaggaa ggggccctgg acgactccgg gtggctcatc 1140

aagaatgtgc tgtccatgcc catcgtcaac aagaaggagg agattgtggg agtcgccaca 1200

ttttacaaca ggaaagacgg gaagcccttt gacgaacagg acgaggttct catggagtcc 1260

ctgacacagt tcctgggctg gtcagtgatg aacaccgaca cctacgacaa gatgaacaag 1320

ctggagaacc gcaaggacat cgcacaggac atggtccttt accacgtgaa gtgcgacagg 1380

gacgagatcc agctcatcct gccaaccaga gcgcgcctgg ggaaggagcc tgctgactgc 1440

gatgaggacg agctgggcga aatcctgaag gaggagctgc cagggcccac cacatttgac 1500

atctacgaat tccacttctc tgacctggag tgcaccgaac tggacctggt caaatgtggc 1560

atccagatgt actacgagct gggcgtggtc cgaaagttcc agatccccca ggaggtcctg 1620

gtgcggttcc tgttctccat cagcaaaggc taccggagaa tcacctacca caactggcgc 1680

cacggcttca acgtggccca gacgatgttc acgctgctca tgaccggcaa actgaagagc 1740

tactacacgg acctggaggc cttcgccatg gtgacagccg gcctgtgcca tgacatcgac 1800

caccgcggca ccaacaacct gtaccagatg aagtcccaga accccttggc taaactccac 1860

ggctcctcga ttttggagcg gcaccacctg gagtttggga agttcctgct ctcggaggag 1920

accctgaaca tctaccagaa cctgaaccgg cggcagcacg agcacgtgat ccacctgatg 1980

gacatcgcca tcatcgccac ggacctggcc ctgtacttca agaagagagc gatgtttcag 2040

aagatcgtgg atgagtccaa gaactaccag gacaagaaga gctgggtgga gtacctgtcc 2100

ctggagacga cccggaagga gatcgtcatg gccatgatga tgacagcctg cgacctgtct 2160

gccatcacca agccctggga agtccagagc aaggtcgcac ttctcgtggc tgctgagttc 2220

tgggagcaag gtgacttgga aaggacagtc ttggatcagc agcccattcc tatgatggac 2280

cggaacaagg cggccgagct ccccaagctg caagtgggct tcatcgactt cgtgtgcaca 2340

ttcgtgtaca aggagttctc tcgtttccac gaagagatcc tgcccatgtt cgaccgactg 2400

cagaacaata ggaaagagtg gaaggcgctg gctgatgagt atgaggccaa agtgaaggct 2460

ctggaggaga aggaggagga ggagagggtg gcagccaaga aagtaggcac agaaatttgc 2520

aatggcggcc cagcacccaa gtcttcaacc tgctgtatcc tgtga 2565

<210> 119

<211> 1497

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(1497)

<223> 甲基-CpG结合蛋白 (MeCP2)

<400> 119

atggccgccg ccgccgccgc cgcgccgagc ggaggaggag gaggaggcga ggaggagaga 60

ctggaagaaa agtcagaaga ccaggacctc cagggcctca aggacaaacc cctcaagttt 120

aaaaaggtga agaaagataa gaaagaagag aaagagggca agcatgagcc cgtgcagcca 180

tcagcccacc actctgctga gcccgcagag gcaggcaaag cagagacatc agaagggtca 240

ggctccgccc cggctgtgcc ggaagcttct gcctccccca aacagcggcg ctccatcatc 300

cgtgaccggg gacccatgta tgatgacccc accctgcctg aaggctggac acggaagctt 360

aagcaaagga aatctggccg ctctgctggg aagtatgatg tgtatttgat caatccccag 420

ggaaaagcct ttcgctctaa agtggagttg attgcgtact tcgaaaaggt aggcgacaca 480

tccctggacc ctaatgattt tgacttcacg gtaactggga gagggagccc ctcccggcga 540

gagcagaaac cacctaagaa gcccaaatct cccaaagctc caggaactgg cagaggccgg 600

ggacgcccca aagggagcgg caccacgaga cccaaggcgg ccacgtcaga gggtgtgcag 660

gtgaaaaggg tcctggagaa aagtcctggg aagctccttg tcaagatgcc ttttcaaact 720

tcgccagggg gcaaggctga ggggggtggg gccaccacat ccacccaggt catggtgatc 780

aaacgccccg gcaggaagcg aaaagctgag gccgaccctc aggccattcc caagaaacgg 840

ggccgaaagc cggggagtgt ggtggcagcc gctgccgccg aggccaaaaa gaaagccgtg 900

aaggagtctt ctatccgatc tgtgcaggag accgtactcc ccatcaagaa gcgcaagacc 960

cgggagacgg tcagcatcga ggtcaaggaa gtggtgaagc ccctgctggt gtccaccctc 1020

ggtgagaaga gcgggaaagg actgaagacc tgtaagagcc ctgggcggaa aagcaaggag 1080

agcagcccca aggggcgcag cagcagcgcc tcctcacccc ccaagaagga gcaccaccac 1140

catcaccacc actcagagtc cccaaaggcc cccgtgccac tgctcccacc cctgccccca 1200

cctccacctg agcccgagag ctccgaggac cccaccagcc cccctgagcc ccaggacttg 1260

agcagcagcg tctgcaaaga ggagaagatg cccagaggag gctcactgga gagcgacggc 1320

tgccccaagg agccagctaa gactcagccc gcggttgcca ccgccgccac ggccgcagaa 1380

aagtacaaac accgagggga gggagagcgc aaagacattg tttcatcctc catgccaagg 1440

ccaaacagag aggagcctgt ggacagccgg acgcccgtga ccgagagagt tagctag 1497

<210> 120

<211> 2232

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(2232)

<223> N-乙酰基-α-氨基葡糖苷酶 (NAGLU)

<400> 120

atggaggcgg tggcggtggc cgcggcggtg ggggtccttc tcctggccgg ggccgggggc 60

gcggcaggcg acgaggcccg ggaggcggcg gccgtgcggg cgctcgtggc ccggctgctg 120

gggccaggcc ccgcggccga cttctccgtg tcggtggagc gcgctctggc tgccaagccg 180

ggcttggaca cctacagcct gggcggcggc ggcgcggcgc gcgtgcgggt gcgcggctcc 240

acgggcgtgg cggccgccgc ggggctgcac cgctacctgc gcgacttctg tggctgccac 300

gtggcctggt ccggctctca gctgcgcctg ccgcggccac tgccagccgt gccgggggag 360

ctgaccgagg ccacgcccaa caggtaccgc tattaccaga atgtgtgcac gcaaagctac 420

tccttcgtgt ggtgggactg ggcccgctgg gagcgagaga tagactggat ggcgctgaat 480

ggcatcaacc tggcactggc ctggagcggc caggaggcca tctggcagcg ggtgtacctg 540

gccttgggcc tgacccaggc agagatcaat gagttcttta ctggtcctgc cttcctggcc 600

tgggggcgaa tgggcaacct gcacacctgg gatggccccc tgcccccctc ctggcacatc 660

aagcagcttt acctgcagca ccgggtcctg gaccagatgc gctccttcgg catgacccca 720

gtgctgcctg cattcgcggg gcatgttccc gaggctgtca ccagggtgtt ccctcaggtc 780

aatgtcacga agatgggcag ttggggccac tttaactgtt cctactcctg ctccttcctt 840

ctggctccgg aagaccccat attccccatc atcgggagcc tcttcctgcg agagctgatc 900

aaagagtttg gcacagacca catctatggg gccgacactt tcaatgagat gcagccacct 960

tcctcagagc cctcctacct tgccgcagcc accactgccg tctatgaggc catgactgca 1020

gtggatactg aggctgtgtg gctgctccaa ggctggctct tccagcacca gccgcagttc 1080

tgggggcccg cccagatcag ggctgtgctg ggagctgtgc cccgtggccg cctcctggtt 1140

ctggacctgt ttgctgagag ccagcctgtg tatacccgca ctgcctcctt ccagggccag 1200

cccttcatct ggtgcatgct gcacaacttt gggggaaacc atggtctttt tggagcccta 1260

gaggctgtga acggaggccc agaagctgcc cgcctcttcc ccaactccac catggtaggc 1320

acgggcatgg cccccgaggg catcagccag aacgaagtgg tctattccct catggctgag 1380

ctgggctggc gaaaggaccc agtgccagat ttggcagcct gggtgaccag ctttgccgcc 1440

cggcggtatg gggtctccca cccggacgca ggggcagcgt ggaggctact gctccggagt 1500

gtgtacaact gctccgggga ggcctgcagg ggccacaatc gtagcccgct ggtcaggcgg 1560

ccgtccctac agatgaatac cagcatctgg tacaaccgat ctgatgtgtt tgaggcctgg 1620

cggctgctgc tcacatctgc tccctccctg gccaccagcc ccgccttccg ctacgacctg 1680

ctggacctca ctcggcaggc agtgcaggag ctggtcagct tgtactatga ggaggcaaga 1740

agcgcctacc tgagcaagga gctggcctcc ctgttgaggg ctggaggcgt cctggcctat 1800

gagctgctgc cggcactgga cgaggtgctg gctagtgaca gccgcttctt gctgggcagc 1860

tggctagagc aggcccgagc agcggcagtc agtgaggccg aggccgattt ctacgagcag 1920

aacagccgct accagctgac cttgtggggg ccagaaggca acatcctgga ctatgccaac 1980

aagcagctgg cggggttggt ggccaactac tacacccctc gctggcggct tttcctggag 2040

gcgctggttg acagtgtggc ccagggcatc cctttccaac agcaccagtt tgacaaaaat 2100

gtcttccaac tggagcaggc cttcgttctc agcaagcaga ggtaccccag ccagccgcga 2160

ggagacactg tggacctggc caagaagatc ttcctcaaat attaccccgg ctgggtggcc 2220

ggctcttggt ga 2232

<210> 121

<211> 1317

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(1317)

<223> 蜡样质脂褐质沉积症神经元蛋白3 (CLN3)

<400> 121

atgggaggct gtgcaggctc gcggcggcgc ttttcggatt ccgaggggga ggagaccgtc 60

ccggagcccc ggctccctct gttggaccat cagggcgcgc attggaagaa cgcggtgggc 120

ttctggctgc tgggcctttg caacaacttc tcttatgtgg tgatgctgag tgccgcccac 180

gacatcctta gccacaagag gacatcggga aaccagagcc atgtggaccc aggcccaacg 240

ccgatccccc acaacagctc atcacgattt gactgcaact ctgtctctac ggctgctgtg 300

ctcctggcgg acatcctccc cacactcgtc atcaaattgt tggctcctct tggccttcac 360

ctgctgccct acagcccccg ggttctcgtc agtgggattt gtgctgctgg aagcttcgtc 420

ctggttgcct tttctcattc tgtggggacc agcctgtgtg gtgtggtctt cgctagcatc 480

tcatcaggcc ttggggaggt caccttcctc tccctcactg ccttctaccc cagggccgtg 540

atctcctggt ggtcctcagg gactggggga gctgggctgc tgggggccct gtcctacctg 600

ggcctcaccc aggccggcct ctcccctcag cagaccctgc tgtccatgct gggtatccct 660

gccctgctgc tggccagcta tttcttgttg ctcacatctc ctgaggccca ggaccctgga 720

ggggaagaag aagcagagag cgcagcccgg cagcccctca taagaaccga ggccccggag 780

tcgaagccag gctccagctc cagcctctcc cttcgggaaa ggtggacagt gttcaagggt 840

ctgctgtggt acattgttcc cttggtcgta gtttactttg ccgagtattt cattaaccag 900

ggactttttg aactcctctt tttctggaac acttccctga gtcacgctca gcaataccgc 960

tggtaccaga tgctgtacca ggctggcgtc tttgcctccc gctcttctct ccgctgctgt 1020

cgcatccgtt tcacctgggc cctggccctg ctgcagtgcc tcaacctggt gttcctgctg 1080

gcagacgtgt ggttcggctt tctgccaagc atctacctcg tcttcctgat cattctgtat 1140

gaggggctcc tgggaggcgc agcctacgtg aacaccttcc acaacatcgc cctggagacc 1200

agtgatgagc accgggagtt tgcaatggcg gccacctgca tctctgacac actggggatc 1260

tccctgtcgg ggctcctggc tttgcctctg catgacttcc tctgccagct ctcctga 1317

<210> 122

<211> 1317

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO1-CLN3

<400> 122

atgggaggat gtgctgggtc aagaagacgg tttagcgatt ccgaaggaga ggagactgtg 60

cctgagccaa gactgcccct gctggatcac cagggagcac actggaagaa cgcagtggga 120

ttctggctgc tgggcctgtg caacaacttc agctacgtgg tcatgctgtc cgccgcccac 180

gacatcctgt cccacaagcg gacctccggc aatcagtctc acgtggaccc cggccctaca 240

ccaatccccc acaacagcag cagccggttc gactgtaatt ccgtgtctac cgcagccgtg 300

ctgctggcag acatcctgcc caccctggtc atcaagctgc tggcaccact gggcctgcac 360

ctgctgcctt attctccaag ggtgctggtg agcggcatct gcgcagcagg cagcttcgtg 420

ctggtggcct ttagccactc cgtgggcacc tctctgtgcg gagtggtgtt tgcaagcatc 480

agctccggcc tgggagaggt gaccttcctg agcctgacag ccttttaccc tcgcgccgtg 540

atctcctggt ggtctagcgg cacaggagga gcaggcctgc tgggcgccct gtcctatctg 600

ggcctgaccc aggcaggcct gtccccacag cagacactgc tgtctatgct gggcatccct 660

gccctgctgc tggcaagcta cttcctgctg ctgacctccc cagaggcaca ggaccccgga 720

ggagaggagg aggccgagag cgccgcaagg cagccactga tcaggaccga ggcaccagag 780

tccaagcctg gctcctctag ctccctgtct ctgcgggaga gatggacagt gttcaagggc 840

ctgctgtggt acatcgtgcc cctggtggtg gtgtacttcg ccgagtactt catcaaccag 900

ggcctgtttg agctgctgtt cttttggaat acctctctga gccacgccca gcagtaccgg 960

tggtatcaga tgctgtatca ggcaggcgtg ttcgcctccc ggtctagcct gagatgctgt 1020

cggatcagat tcacctgggc actggccctg ctgcagtgcc tgaacctggt gttcctgctg 1080

gccgacgtgt ggttcggctt tctgccctct atctacctgg tgtttctgat catcctgtat 1140

gagggcctgc tgggaggagc agcctatgtg aacaccttcc acaatatcgc cctggagaca 1200

tctgacgagc acagagagtt tgctatggcc gccacctgta tcagcgatac actgggcatc 1260

tctctgagcg gactgctggc tctgcctctg catgactttc tgtgccagct gagttaa 1317

<210> 123

<211> 2859

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(2859)

<223> 酸性α-葡糖苷酶 (GAA)

<400> 123

atgggagtga ggcacccgcc ctgctcccac cggctcctgg ccgtctgcgc cctcgtgtcc 60

ttggcaaccg ctgcactcct ggggcacatc ctactccatg atttcctgct ggttccccga 120

gagctgagtg gctcctcccc agtcctggag gagactcacc cagctcacca gcagggagcc 180

agcagaccag ggccccggga tgcccaggca caccccggcc gtcccagagc agtgcccaca 240

cagtgcgacg tcccccccaa cagccgcttc gattgcgccc ctgacaaggc catcacccag 300

gaacagtgcg aggcccgcgg ctgttgctac atccctgcaa agcaggggct gcagggagcc 360

cagatggggc agccctggtg cttcttccca cccagctacc ccagctacaa gctggagaac 420

ctgagctcct ctgaaatggg ctacacggcc accctgaccc gtaccacccc caccttcttc 480

cccaaggaca tcctgaccct gcggctggac gtgatgatgg agactgagaa ccgcctccac 540

ttcacgatca aagatccagc taacaggcgc tacgaggtgc ccttggagac cccgcatgtc 600

cacagccggg caccgtcccc actctacagc gtggagttct ccgaggagcc cttcggggtg 660

atcgtgcgcc ggcagctgga cggccgcgtg ctgctgaaca cgacggtggc gcccctgttc 720

tttgcggacc agttccttca gctgtccacc tcgctgccct cgcagtatat cacaggcctc 780

gccgagcacc tcagtcccct gatgctcagc accagctgga ccaggatcac cctgtggaac 840

cgggaccttg cgcccacgcc cggtgcgaac ctctacgggt ctcacccttt ctacctggcg 900

ctggaggacg gcgggtcggc acacggggtg ttcctgctaa acagcaatgc catggatgtg 960

gtcctgcagc cgagccctgc ccttagctgg aggtcgacag gtgggatcct ggatgtctac 1020

atcttcctgg gcccagagcc caagagcgtg gtgcagcagt acctggacgt tgtgggatac 1080

ccgttcatgc cgccatactg gggcctgggc ttccacctgt gccgctgggg ctactcctcc 1140

accgctatca cccgccaggt ggtggagaac atgaccaggg cccacttccc cctggacgtc 1200

cagtggaacg acctggacta catggactcc cggagggact tcacgttcaa caaggatggc 1260

ttccgggact tcccggccat ggtgcaggag ctgcaccagg gcggccggcg ctacatgatg 1320

atcgtggatc ctgccatcag cagctcgggc cctgccggga gctacaggcc ctacgacgag 1380

ggtctgcgga ggggggtttt catcaccaac gagaccggcc agccgctgat tgggaaggta 1440

tggcccgggt ccactgcctt ccccgacttc accaacccca cagccctggc ctggtgggag 1500

gacatggtgg ctgagttcca tgaccaggtg cccttcgacg gcatgtggat tgacatgaac 1560

gagccttcca acttcatcag gggctctgag gacggctgcc ccaacaatga gctggagaac 1620

ccaccctacg tgcctggggt ggttgggggg accctccagg cggccaccat ctgtgcctcc 1680

agccaccagt ttctctccac acactacaac ctgcacaacc tctacggcct gaccgaagcc 1740

atcgcctccc acagggcgct ggtgaaggct cgggggacac gcccatttgt gatctcccgc 1800

tcgacctttg ctggccacgg ccgatacgcc ggccactgga cgggggacgt gtggagctcc 1860

tgggagcagc tcgcctcctc cgtgccagaa atcctgcagt ttaacctgct gggggtgcct 1920

ctggtcgggg ccgacgtctg cggcttcctg ggcaacacct cagaggagct gtgtgtgcgc 1980

tggacccagc tgggggcctt ctaccccttc atgcggaacc acaacagcct gctcagtctg 2040

ccccaggagc cgtacagctt cagcgagccg gcccagcagg ccatgaggaa ggccctcacc 2100

ctgcgctacg cactcctccc ccacctctac acactgttcc accaggccca cgtcgcgggg 2160

gagaccgtgg cccggcccct cttcctggag ttccccaagg actctagcac ctggactgtg 2220

gaccaccagc tcctgtgggg ggaggccctg ctcatcaccc cagtgctcca ggccgggaag 2280

gccgaagtga ctggctactt ccccttgggc acatggtacg acctgcagac ggtgccagta 2340

gaggcccttg gcagcctccc acccccacct gcagctcccc gtgagccagc catccacagc 2400

gaggggcagt gggtgacgct gccggccccc ctggacacca tcaacgtcca cctccgggct 2460

gggtacatca tccccctgca gggccctggc ctcacaacca cagagtcccg ccagcagccc 2520

atggccctgg ctgtggccct gaccaagggt ggggaggccc gaggggagct gttctgggac 2580

gatggagaga gcctggaagt gctggagcga ggggcctaca cacaggtcat cttcctggcc 2640

aggaataaca cgatcgtgaa tgagctggta cgtgtgacca gtgagggagc tggcctgcag 2700

ctgcagaagg tgactgtcct gggcgtggcc acggcgcccc agcaggtcct ctccaacggt 2760

gtccctgtct ccaacttcac ctacagcccc gacaccaagg tcctggacat ctgtgtctcg 2820

ctgttgatgg gagagcagtt tctcgtcagc tggtgttag 2859

<210> 124

<211> 2859

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO1-GAA

<400> 124

atgggagtcc gccacccgcc ctgctcacat cgcctgcttg ctgtctgtgc cctcgtgtca 60

cttgctaccg ccgcgctgct tggtcacatt ctgctgcacg actttttact agttccgagg 120

gaactgtcgg gatccagccc cgtgctcgag gaaactcacc ccgcgcacca acagggggcg 180

tccaggccgg gaccgcgcga cgcccaggcc cacccgggcc ggcctcgggc cgtgccaact 240

cagtgcgatg tgccgccgaa ctcccgcttc gactgtgcgc ctgacaaggc cataacccag 300

gaacagtgcg aagcacgcgg ctgctgctat attccggcga agcagggctt gcagggtgcc 360

caaatgggtc agccttggtg cttctttccc ccgtcgtacc cctcgtacaa gctggagaac 420

ctgagcagca gcgaaatggg gtacaccgcc actctgaccc ggacgacccc gaccttcttc 480

ccgaaagaca tcctgaccct gcggctggat gtgatgatgg aaactgagaa cagactgcac 540

ttcactatca aggaccccgc gaaccgcaga tatgaggtgc cactggaaac ccctcatgtg 600

cattcccggg ccccatcccc tctgtactcg gtggaattct ccgaagaacc cttcggggtc 660

attgtgcgcc ggcagcttga tggccgggtc ctgctcaaca ccaccgtggc accccttttc 720

ttcgctgacc agttcctcca gctgagcacc tcgctgccga gccagtacat caccggactg 780

gccgagcacc tctcccctct gatgctgtcc actagctgga ctaggatcac tctgtggaac 840

cgggatctgg cccctacccc gggcgcgaac ctgtacggat cgcacccctt ctacctggcc 900

ctcgaggacg gaggctccgc ccacggagtg ttcctgctga actccaacgc tatggacgtg 960

gtgctccagc cgtcccctgc actgtcctgg cggagcacag ggggtattct ggatgtctac 1020

atcttcctcg gcccggagcc aaagtccgtg gtgcaacagt atctggatgt cgtgggttac 1080

ccattcatgc cgccatactg gggccttggc ttccacctgt gccgctgggg atacagctcc 1140

accgccatca ctagacaggt cgtggaaaac atgactagag cccacttccc cctcgatgtc 1200

cagtggaatg acctggacta catggattcc agacgcgact tcactttcaa caaggatgga 1260

ttcagagatt tccccgctat ggtccaagaa ctgcaccagg gtggccggcg gtacatgatg 1320

attgtggacc ccgccatttc aagctccgga ccagcgggct cgtaccggcc ctacgacgaa 1380

ggtttgcgcc gcggcgtgtt catcactaac gaaaccggcc agccactgat tgggaaggtc 1440

tggcctggaa gcaccgcgtt cccggacttc actaacccaa cggccttggc gtggtgggag 1500

gacatggtgg ccgaattcca cgaccaagtc ccattcgacg gaatgtggat cgacatgaac 1560

gagcccagca acttcatccg aggctccgag gacggctgcc ctaacaacga acttgagaac 1620

cctccgtacg tgcctggcgt cgtcggcgga acactgcagg ccgctacgat ctgtgcctca 1680

tcgcatcagt tcctgtcaac ccactacaac ctccataatc tgtacggcct caccgaagcc 1740

atcgcctccc accgggccct ggtcaaggcc cgggggacta ggcccttcgt gattagccgg 1800

agcactttcg ccggacacgg aagatacgcc ggacattgga ccggcgacgt gtggtcatcg 1860

tgggagcagc tcgcctcctc cgtccccgaa atcctgcagt tcaatctcct gggagtcccc 1920

ctcgtgggcg cggacgtgtg cggattcctg ggcaatacct ctgaggagct gtgcgtgaga 1980

tggacccagc tgggggcgtt ctaccccttc atgcggaacc acaactcact gctgtccctg 2040

cctcaagagc cgtactcatt ctccgagccg gcacaacagg ccatgcgaaa ggctctgacc 2100

ctccgctatg cgctcttgcc ccacctctac actctgtttc accaagccca tgtcgcgggc 2160

gaaacagtgg ccagaccact ctttctggaa ttcccaaagg actcctcaac ctggactgtg 2220

gatcatcagc tgctctgggg agaggcactg ctgatcaccc cggtgctcca agccggaaag 2280

gcggaagtga ccggatactt ccctctcggt acttggtacg acctccaaac cgtgccggtc 2340

gaggccctgg gcagcttgcc tccgccgccg gctgccccgc gggagcctgc aatccactcc 2400

gaggggcaat gggtgaccct ccctgcacca ctggacacca tcaacgtgca cctccgggcc 2460

ggctacatca tcccgctgca aggaccgggt ctgactacca ccgaatcccg gcagcagccc 2520

atggcactgg ccgtggccct gaccaaggga ggggaagcac ggggagaact cttttgggac 2580

gatggagaat ccctggaagt gctcgagcgg ggagcctaca ctcaagtcat ctttcttgcc 2640

cgcaacaaca ccatcgtgaa cgaattggtc cgcgtgacct ccgagggggc cggactccag 2700

ctgcaaaaag tgaccgtgct gggggtggca accgccccgc aacaagtgtt gtctaacgga 2760

gtgccggtgt ccaacttcac ctactcccct gataccaaag ttctagatat ttgcgtgagc 2820

ctgctgatgg gagaacagtt cctggtgtcc tggtgctga 2859

<210> 125

<211> 2859

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO2-GAA

<400> 125

atgggagtta gacaccctcc atgtagccac agactgctgg ccgtgtgtgc tctggtgtct 60

ctggctacag ctgccctgct gggacatatc ctgctgcacg acttcttact agttcccaga 120

gagctgtccg gcagcagccc tgtgctggaa gaaacacacc ctgcacatca gcagggcgcc 180

tctagacctg gacctagaga tgctcaggcc catcctggca gacctagagc tgtgcccaca 240

cagtgtgacg tgccacctaa cagcagattc gactgcgccc ctgacaaggc catcacacaa 300

gagcagtgtg aagccagagg ctgctgctac atccctgcca aacaaggact gcagggcgct 360

cagatgggac agccctggtg cttcttccca ccatcttacc ccagctacaa gctggaaaac 420

ctgagcagca gcgagatggg ctacaccgcc acactgacca gaaccacacc tacattcttc 480

ccgaaggaca tcctgacact gcggctggac gtgatgatgg aaaccgagaa ccggctgcac 540

ttcaccatca aggaccccgc caatcggaga tacgaggtgc cactggaaac ccctcacgtg 600

cactctagag ccccatctcc actgtacagc gtggaattca gcgaggaacc cttcggcgtg 660

atcgtgcgga gacagctgga tggaagagtg ctgctgaaca ccacagtggc ccctctgttc 720

ttcgccgacc agtttctgca gctgtccacc agcctgccta gccagtatat cacaggcctg 780

gccgagcacc tgtctccact gatgctgtct accagctgga cccggatcac cctgtggaac 840

agggatcttg ctcctacacc tggcgccaac ctgtacggct ctcacccttt ttatctggcc 900

ctggaagatg gcggatctgc ccacggtgtc tttctgctga actccaacgc catggacgtg 960

gtgctgcagc catctcctgc tctgtcttgg agaagcacag gcggcatcct ggacgtgtac 1020

atctttctgg gccccgagcc taagagcgtg gtgcagcagt atctggacgt cgtgggctac 1080

cccttcatgc ctccttattg gggcctgggc ttccacctgt gcagatgggg atacagcagc 1140

accgccatca ccagacaggt ggtggaaaac atgacccggg ctcacttccc actggatgtg 1200

cagtggaacg acctggacta catggacagc agacgggact tcaccttcaa caaggacggc 1260

ttcagagact tccccgccat ggtgcaagaa ctgcaccaag gcggcagacg gtacatgatg 1320

atcgtggatc cagccatcag ctctagcggc cctgccggct cttacagacc ttacgatgag 1380

ggcctgagaa gaggcgtgtt catcaccaac gagacaggcc agcctctgat cggcaaagtg 1440

tggcctggca gcacagcctt tccagacttc acaaacccca ccgctctggc ttggtgggaa 1500

gatatggtgg ccgagtttca cgatcaggtg cccttcgacg gcatgtggat cgacatgaac 1560

gagcccagca acttcatccg gggcagcgag gatggctgcc ccaacaacga actggaaaat 1620

cctccttacg tgcccggcgt tgtcggcgga acacttcagg ccgctacaat ctgtgccagc 1680

agccaccagt tcctcagcac ccactacaac ctgcacaatc tgtatggcct gaccgaggcc 1740

attgccagcc atagagccct ggttaaggcc aggggcacca gacctttcgt gatcagcaga 1800

agcaccttcg ccggccacgg cagatatgcc ggacattgga caggcgacgt gtggtctagt 1860

tgggagcagc tggctagcag cgtgccagag atcctgcagt tcaatctgct gggcgtgcca 1920

ctcgtgggag ccgatgtttg tggcttcctg ggcaacacct ccgaggaact gtgtgtgcgt 1980

tggacacagc tgggcgcctt ctatcccttc atgagaaacc acaacagcct tctcagcctg 2040

ccacaagagc cctacagctt ctctgagcct gcacagcagg ccatgagaaa ggccctgact 2100

ctgagatacg ctctgctgcc ccacctgtac accctgtttc accaggctca tgtggccggg 2160

gagacagtgg ctagacctct gttcctggaa ttccccaagg acagctccac ctggaccgtg 2220

gatcatcagc tgctgtgggg agaagccctg ctcatcacac ctgttctgca ggccggaaag 2280

gccgaagtga ccggctattt tcctctcggc acttggtacg acctgcagac cgtgcctgtt 2340

gaggctctgg gatctcttcc tccacctcct gccgctccta gagagcctgc cattcactct 2400

gaaggccagt gggttaccct gcctgctcct ctggacacca tcaacgtgca cctgagagct 2460

ggctacatca tccctctgca aggccctggc ctgacaacca ccgaatctag acagcagccc 2520

atggctctgg ccgtggcttt gacaaaaggc ggagaggcta gaggcgagct gttctgggat 2580

gatggcgaga gcctggaagt gctggaacgg ggcgcttata cccaagtgat cttcctggcc 2640

agaaacaaca ccatcgtgaa cgaactcgtg cgcgtgacca gtgaaggtgc tggactgcaa 2700

ctgcagaaag tgaccgtgct cggagtggcc acagcacctc agcaggttct gtctaatggc 2760

gtgcccgtgt ccaacttcac atacagcccc gacaccaagg tcctggacat ctgtgtgtca 2820

ctgctgatgg gcgagcagtt cctggtgtcc tggtgttga 2859

<210> 126

<211> 2859

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO3-GAA

<400> 126

atgggggtga gacacccccc ctgcagccac agactgctgg ctgtgtgtgc cctggtgagc 60

ctggccacag ctgccctgct gggccacatc ctgctgcatg acttcctact agtgcccaga 120

gagctgagtg gcagcagccc tgtgctggag gagacccacc ctgcccacca gcagggggcc 180

agcagacctg gccccagaga tgcccaggcc caccctggca gacccagagc tgtgcccacc 240

cagtgtgatg tgccccccaa cagcagattt gactgtgccc ctgacaaggc catcacccag 300

gagcagtgtg aggccagagg ctgctgctac atccctgcca agcagggcct gcagggggcc 360

cagatgggcc agccctggtg cttcttcccc cccagctacc ccagctacaa gctggagaac 420

ctgagcagca gtgagatggg ctacacagcc accctgacca gaaccacccc caccttcttc 480

cccaaggaca tcctgaccct gagactggat gtgatgatgg agacagagaa cagactgcac 540

ttcaccatca aggaccctgc caacagaaga tatgaggtgc ccctggagac cccccatgtg 600

cacagcagag cccccagccc cctgtacagt gtggagttca gtgaggagcc ctttggggtg 660

attgtgagaa gacagctgga tggcagagtg ctgctgaaca ccacagtggc ccccctgttc 720

tttgctgacc agttcctgca gctgagcacc agcctgccca gccagtacat cacaggcctg 780

gctgagcacc tgagccccct gatgctgagc accagctgga ccagaatcac cctgtggaac 840

agagacctgg cccccacccc tggggccaac ctgtatggca gccacccctt ctacctggcc 900

ctggaggatg ggggcagtgc ccatggggtg ttcctgctga acagcaatgc catggatgtg 960

gtgctgcagc ccagccctgc cctgagctgg agaagcacag ggggcatcct ggatgtgtac 1020

atcttcctgg gccctgagcc caagagtgtg gtgcagcagt acctggatgt ggtgggctac 1080

cccttcatgc ccccctactg gggcctgggc ttccacctgt gcagatgggg ctacagcagc 1140

acagccatca ccagacaggt ggtggagaac atgaccagag cccacttccc cctggatgtg 1200

cagtggaatg acctggacta catggacagc agaagagact tcaccttcaa caaggatggc 1260

ttcagagact tccctgccat ggtgcaggag ctgcaccagg ggggcagaag atacatgatg 1320

attgtggacc ctgccatcag cagcagtggc cctgctggca gctacagacc ctatgatgag 1380

ggcctgagaa gaggggtgtt catcaccaat gagacaggcc agcccctgat tggcaaggtg 1440

tggcctggca gcacagcctt ccctgacttc accaacccca cagccctggc ctggtgggag 1500

gacatggtgg ctgagttcca tgaccaggtg ccctttgatg gcatgtggat tgacatgaat 1560

gagcccagca acttcatcag aggcagtgag gatggctgcc ccaacaatga gctggagaac 1620

cccccctatg tgcctggggt ggtggggggc accctgcagg ctgccaccat ctgtgccagc 1680

agccaccagt tcctgagcac ccactacaac ctgcacaacc tgtatggcct gacagaggcc 1740

attgccagcc acagagccct ggtgaaggcc agaggcacca gaccctttgt gatcagcaga 1800

agcacctttg ctggccatgg cagatatgct ggccactgga caggggatgt gtggagcagc 1860

tgggagcagc tggccagcag tgtgcctgag atcctgcagt tcaacctgct gggggtgccc 1920

ctggtggggg ctgatgtgtg tggcttcctg ggcaacacca gtgaggagct gtgtgtgaga 1980

tggacccagc tgggggcctt ctaccccttc atgagaaacc acaacagcct gctgagcctg 2040

ccccaggagc cctacagctt cagtgagcct gcccagcagg ccatgagaaa ggccctgacc 2100

ctgagatatg ccctgctgcc ccacctgtac accctgttcc accaggccca tgtggctggg 2160

gagacagtgg ccagacccct gttcctggag ttccccaagg acagcagcac ctggacagtg 2220

gaccaccagc tgctgtgggg ggaggccctg ctgatcaccc ctgtgctgca ggctggcaag 2280

gctgaggtga caggctactt ccccctgggc acctggtatg acctgcagac agtgcctgtg 2340

gaggccctgg gcagcctgcc ccccccccct gctgccccca gagagcctgc catccacagt 2400

gagggccagt gggtgaccct gcctgccccc ctggacacca tcaatgtgca cctgagagct 2460

ggctacatca tccccctgca gggccctggc ctgaccacca cagagagcag acagcagccc 2520

atggccctgg ctgtggccct gaccaagggg ggggaggcca gaggggagct gttctgggat 2580

gatggggaga gcctggaggt gctggagaga ggggcctaca cccaggtgat cttcctggcc 2640

agaaacaaca ccattgtgaa tgagctggtg agagtgacca gtgagggggc tggcctgcag 2700

ctgcagaagg tgacagtgct gggggtggcc acagcccccc agcaggtgct gagcaatggg 2760

gtgcctgtga gcaacttcac ctacagccct gacaccaagg tgctggacat ctgtgtgagc 2820

ctgctgatgg gggagcagtt cctggtgagc tggtgctga 2859

<210> 127

<211> 1290

<212> DNA

<213> 智人

<220>

<221> misc_feature

<222> (1)..(1290)

<223> α-半乳糖苷酶 A (GLA)

<400> 127

atgcagctga ggaacccaga actacatctg ggctgcgcgc ttgcgcttcg cttcctggcc 60

ctcgtttcct gggacatccc tggggctaga gcactggaca atggattggc aaggacgcct 120

accatgggct ggctgcactg ggagcgcttc atgtgcaacc ttgactgcca ggaagagcca 180

gattcctgca tcagtgagaa gctcttcatg gagatggcag agctcatggt ctcagaaggc 240

tggaaggatg caggttatga gtacctctgc attgatgact gttggatggc tccccaaaga 300

gattcagaag gcagacttca ggcagaccct cagcgctttc ctcatgggat tcgccagcta 360

gctaattatg ttcacagcaa aggactgaag ctagggattt atgcagatgt tggaaataaa 420

acctgcgcag gcttccctgg gagttttgga tactacgaca ttgatgccca gacctttgct 480

gactggggag tagatctgct aaaatttgat ggttgttact gtgacagttt ggaaaatttg 540

gcagatggtt ataagcacat gtccttggcc ctgaatagga ctggcagaag cattgtgtac 600

tcctgtgagt ggcctcttta tatgtggccc tttcaaaagc ccaattatac agaaatccga 660

cagtactgca atcactggcg aaattttgct gacattgatg attcctggaa aagtataaag 720

agtatcttgg actggacatc ttttaaccag gagagaattg ttgatgttgc tggaccaggg 780

ggttggaatg acccagatat gttagtgatt ggcaactttg gcctcagctg gaatcagcaa 840

gtaactcaga tggccctctg ggctatcatg gctgctcctt tattcatgtc taatgacctc 900

cgacacatca gccctcaagc caaagctctc cttcaggata aggacgtaat tgccatcaat 960

caggacccct tgggcaagca agggtaccag cttagacagg gagacaactt tgaagtgtgg 1020

gaacgacctc tctcaggctt agcctgggct gtagctatga taaaccggca ggagattggt 1080

ggacctcgct cttataccat cgcagttgct tccctgggta aaggagtggc ctgtaatcct 1140

gcctgcttca tcacacagct cctccctgtg aaaaggaagc tagggttcta tgaatggact 1200

tcaaggttaa gaagtcacat aaatcccaca ggcactgttt tgcttcagct agaaaataca 1260

atgcagatgt cattaaaaga cttactttaa 1290

<210> 128

<211> 1290

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO1-GLA

<400> 128

atgcagctga gaaatcctga actgcacctg ggctgtgccc tggctctgag atttctggct 60

ctggtgtcct gggacattcc tggcgctaga gccctggata atggcctggc cagaacacct 120

acaatgggct ggctgcactg ggagagattc atgtgcaacc tggactgcca agaggaaccc 180

gacagctgca tcagcgagaa gctgttcatg gaaatggccg agctgatggt gtccgaaggc 240

tggaaggatg ccggctacga gtacctgtgc atcgacgatt gctggatggc ccctcagaga 300

gattctgagg gcagactgca ggccgatcct cagagatttc ctcacggaat ccggcagctg 360

gccaactacg tgcactctaa gggactgaag ctgggcatct acgccgacgt gggcaacaag 420

acatgtgccg gctttccagg cagcttcggc tactacgata tcgacgccca gacctttgcc 480

gattggggcg tcgacctgct gaagttcgat ggctgctact gcgacagcct ggaaaacctg 540

gccgacggct acaaacacat gtctctggcc ctgaaccgga ccggcagatc tatcgtgtac 600

tcttgcgagt ggcccctgta catgtggccc ttccagaagc ctaactacac cgagatcaga 660

cagtactgca accactggcg gaacttcgcc gacatcgatg acagctggaa gtccatcaag 720

agcatcctgg actggaccag cttcaatcaa gagcggatcg tggatgtggc tggcccaggc 780

ggatggaacg atcctgatat gctggtcatc ggcaacttcg gcctgagctg gaatcagcaa 840

gtgacccaga tggccctgtg ggccattatg gccgctcctc tgttcatgag caacgacctg 900

agacacatca gccctcaggc caaggctctg ctgcaggata aggacgtgat cgccatcaac 960

caggatcctc tgggcaagca gggctatcag ctgagacagg gcgacaattt cgaagtgtgg 1020

gaaagacctc tgagcggcct ggcttgggcc gtcgccatga tcaatagaca agagatcggc 1080

ggaccccggt cctatacaat tgccgtggct tctctcggaa aaggcgtggc ctgcaatcct 1140

gcctgcttta tcacacagct gctccccgtg aagagaaagc tgggctttta cgagtggacc 1200

agcagactga gatcccacat caaccccaca ggcactgttc tgctgcaact ggaaaacaca 1260

atgcagatga gcctgaagga cctgctgtag 1290

<210> 129

<211> 1377

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的+ GET, CO1-GLA-GET

<400> 129

atgcagctga gaaatcctga actgcacctg ggctgtgccc tggctctgag atttctggct 60

ctggtgtcct gggacattcc tggcgctaga gccctggata atggcctggc cagaacacct 120

acaatgggct ggctgcactg ggagagattc atgtgcaacc tggactgcca agaggaaccc 180

gacagctgca tcagcgagaa gctgttcatg gaaatggccg agctgatggt gtccgaaggc 240

tggaaggatg ccggctacga gtacctgtgc atcgacgatt gctggatggc ccctcagaga 300

gattctgagg gcagactgca ggccgatcct cagagatttc ctcacggaat ccggcagctg 360

gccaactacg tgcactctaa gggactgaag ctgggcatct acgccgacgt gggcaacaag 420

acatgtgccg gctttccagg cagcttcggc tactacgata tcgacgccca gacctttgcc 480

gattggggcg tcgacctgct gaagttcgat ggctgctact gcgacagcct ggaaaacctg 540

gccgacggct acaaacacat gtctctggcc ctgaaccgga ccggcagatc tatcgtgtac 600

tcttgcgagt ggcccctgta catgtggccc ttccagaagc ctaactacac cgagatcaga 660

cagtactgca accactggcg gaacttcgcc gacatcgatg acagctggaa gtccatcaag 720

agcatcctgg actggaccag cttcaatcaa gagcggatcg tggatgtggc tggcccaggc 780

ggatggaacg atcctgatat gctggtcatc ggcaacttcg gcctgagctg gaatcagcaa 840

gtgacccaga tggccctgtg ggccattatg gccgctcctc tgttcatgag caacgacctg 900

agacacatca gccctcaggc caaggctctg ctgcaggata aggacgtgat cgccatcaac 960

caggatcctc tgggcaagca gggctatcag ctgagacagg gcgacaattt cgaagtgtgg 1020

gaaagacctc tgagcggcct ggcttgggcc gtcgccatga tcaatagaca agagatcggc 1080

ggaccccggt cctatacaat tgccgtggct tctctcggaa aaggcgtggc ctgcaatcct 1140

gcctgcttta tcacacagct gctccccgtg aagagaaagc tgggctttta cgagtggacc 1200

agcagactga gatcccacat caaccccaca ggcactgttc tgctgcaact ggaaaacaca 1260

atgcagatga gcctgaagga cctgctgcgg agaagaagaa ggcgcagacg caagcgcaag 1320

aagaaaggca aaggcctcgg caagaagcgg gacccctgtc tgagaaagta caagtaa 1377

<210> 130

<211> 1290

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO2-GLA

<400> 130

atgcagctga gaaaccctga gctgcacctg ggctgtgccc tggccctgag attcctggcc 60

ctggtgagct gggacatccc tggggccaga gccctggaca atgggctagc cagaaccccc 120

accatgggct ggctgcactg ggagagattc atgtgcaacc tggactgcca ggaggagcct 180

gacagctgca tcagtgagaa gctgttcatg gagatggctg agctgatggt gagtgagggc 240

tggaaggatg ctggctatga gtacctgtgc attgatgact gctggatggc cccccagaga 300

gacagtgagg gcagactgca ggctgacccc cagagattcc cccatggcat cagacagctg 360

gccaactatg tgcacagcaa gggcctgaag ctgggcatct atgctgatgt gggcaacaag 420

acctgtgctg gcttccctgg cagctttggc tactatgaca ttgatgccca gacctttgct 480

gactgggggg tggacctgct gaagtttgat ggctgctact gtgacagcct ggagaacctg 540

gctgatggct acaagcacat gagcctggcc ctgaacagaa caggcagaag cattgtgtac 600

agctgtgagt ggcccctgta catgtggccc ttccagaagc ccaactacac agagatcaga 660

cagtactgca accactggag aaactttgct gacattgatg acagctggaa gagcatcaag 720

agcatcctgg actggaccag cttcaaccag gagagaattg tggatgtggc tggccctggg 780

ggctggaatg accctgacat gctggtgatt ggcaactttg gcctgagctg gaaccagcag 840

gtgacccaga tggccctgtg ggccatcatg gctgcccccc tgttcatgag caatgacctg 900

agacacatca gcccccaggc caaggccctg ctgcaggaca aggatgtgat tgccatcaac 960

caggaccccc tgggcaagca gggctaccag ctgagacagg gggacaactt tgaggtgtgg 1020

gagagacccc tgagtggcct ggcctgggct gtggccatga tcaacagaca ggagattggg 1080

ggccccagaa gctacaccat tgctgtggcc agcctgggca agggggtggc ctgcaaccct 1140

gcctgcttca tcacccagct gctgcctgtg aagagaaagc tgggcttcta tgagtggacc 1200

agcagactga gaagccacat caaccccaca ggcacagtgc tgctgcagct ggagaacacc 1260

atgcagatga gcctgaagga cctgctgtga 1290

<210> 131

<211> 1290

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的CO3-GLA

<400> 131

atgcagctga gaaaccctga gctgcacctg ggctgtgccc tggccctgag attcctggcc 60

ctggtgagct gggacatccc tggggccaga gccctggaca atgggctagc cagaaccccc 120

accatgggct ggctgcactg ggagagattc atgtgcaacc tggactgcca ggaggagcct 180

gacagctgca tcagtgagaa gctgttcatg gagatggctg agctgatggt gagtgagggc 240

tggaaggatg ctggctatga gtacctgtgc attgatgact gctggatggc cccccagaga 300

gacagtgagg gcagactgca ggctgacccc cagagattcc cccatggcat cagacagctg 360

gccaactatg tgcacagcaa gggcctgaag ctgggcatct atgctgatgt gggcaacaag 420

acctgtgctg gcttccctgg cagctttggc tactatgaca ttgatgccca gacctttgct 480

gactgggggg tggacctgct gaagtttgat ggctgctact gtgacagcct ggagaacctg 540

gctgatggct acaagcacat gagcctggcc ctgaacagaa caggcagaag cattgtgtac 600

agctgtgagt ggcccctgta catgtggccc ttccagaagc ccaactacac agagatcaga 660

cagtactgca accactggag aaactttgct gacattgatg acagctggaa gagcatcaag 720

agcatcctgg actggaccag cttcaaccag gagagaattg tggatgtggc tggccctggg 780

ggctggaatg accctgacat gctggtgatt ggcaactttg gcctgagctg gaaccagcag 840

gtgacccaga tggccctgtg ggccatcatg gctgcccccc tgttcatgag caatgacctg 900

agacacatca gcccccaggc caaggccctg ctgcaggaca aggatgtgat tgccatcaac 960

caggaccccc tgggcaagca gggctaccag ctgagacagg gggacaactt tgaggtgtgg 1020

gagagacccc tgagtggcct ggcctgggct gtggccatga tcaacagaca ggagattggg 1080

ggccccagaa gctacaccat tgctgtggct tccctgggta aaggagtggc ctgtaatcct 1140

gcctgcttca tcacacagct cctccctgtg aaaaggaagc tagggttcta tgaatggact 1200

tcaaggttaa gaagtcacat aaatcccaca ggcactgttt tgcttcagct agaaaataca 1260

atgcagatgt cattaaaaga cttactttaa 1290

<210> 132

<211> 4287

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的，囊性纤维化跨膜调节蛋白ΔR

(CFTR△R)含有R结构域缺失

<400> 132

atgcagagaa gccccctgga gaaggcctct gtggtgagca agctgttctt cagctggacc 60

agacccatcc tgagaaaggg ctacagacag agactggagc tgtctgacat ctaccagatc 120

ccctctgtgg actctgctga caacctgtct gagaagctgg agagagagtg ggacagagag 180

ctggccagca agaagaaccc caagctgatc aatgccctga gaagatgctt cttctggaga 240

ttcatgttct atggcatctt cctgtacctg ggggaggtga ccaaggctgt gcagcccctg 300

ctgctgggca gaatcattgc cagctatgac cctgacaaca aggaggagag aagcattgcc 360

atctacctgg gcattggcct gtgcctgctg ttcattgtga gaaccctgct gctgcaccct 420

gccatctttg gcctgcacca cattggcatg cagatgagaa ttgccatgtt cagcctgatc 480

tacaagaaga ccctgaagct gagcagcaga gtgctggaca agatcagcat tggccagctg 540

gtgagcctgc tgagcaacaa cctgaacaag tttgatgagg gcctggccct ggcccacttt 600

gtgtggattg cccccctgca ggtggccctg ctgatgggcc tgatctggga gctgctgcag 660

gcctctgcct tctgtggcct gggcttcctg attgtgctgg ccctgttcca ggctggcctg 720

ggcagaatga tgatgaagta cagagaccag agagctggca agatctctga gagactggtg 780

atcacctctg agatgattga gaacatccag tctgtgaagg cctactgctg ggaggaggcc 840

atggagaaga tgattgagaa cctgagacag acagagctga agctgaccag aaaggctgcc 900

tatgtgagat acttcaacag ctctgccttc ttcttctctg gcttctttgt ggtgttcctg 960

tctgtgctgc cctatgccct gatcaagggc atcatcctga gaaagatctt caccaccatc 1020

agcttctgca ttgtgctgag aatggctgtg accagacagt tcccctgggc tgtgcagacc 1080

tggtatgaca gcctgggggc catcaacaag atccaggact tcctgcagaa gcaggagtac 1140

aagaccctgg agtacaacct gaccaccaca gaggtggtga tggagaatgt gacagccttc 1200

tgggaggagg gctttgggga gctgtttgag aaggccaagc agaacaacaa caacagaaag 1260

accagcaatg gggatgacag cctgttcttc agcaacttca gcctgctggg cacccctgtg 1320

ctgaaggaca tcaacttcaa gattgagaga ggccagctgc tggctgtggc tggcagcaca 1380

ggggctggca agaccagcct gctgatgatg atcatggggg agctggagcc ctctgagggc 1440

aagatcaagc actctggcag aatcagcttc tgcagccagt tcagctggat catgcctggc 1500

accatcaagg agaacatcat ctttggggtg agctatgatg agtacagata cagatctgtg 1560

atcaaggcct gccagctgga ggaggacatc agcaagtttg ctgagaagga caacattgtg 1620

ctgggggagg ggggcatcac cctgtctggg ggccagagag ccagaatcag cctggccaga 1680

gctgtgtaca aggatgctga cctgtacctg ctggacagcc cctttggcta cctggatgtg 1740

ctgacagaga aggagatctt tgagagctgt gtgtgcaagc tgatggccaa caagaccaga 1800

atcctggtga ccagcaagat ggagcacctg aagaaggctg acaagatcct gatcctgcat 1860

gagggcagca gctacttcta tggcaccttc tctgagctgc agaacctgca gcctgacttc 1920

agcagcaagc tgatgggctg tgacagcttt gaccagttct ctgctgagag aagaaacagc 1980

atcctgacag agaccctgca cagattcagc ctggaggggg atgcccctgt gagctggaca 2040

gagaccaaga agcagagctt caagcagaca ggggagtttg gggagaagag aaagaacagc 2100

atcctgaacc ccatcaacag caccctgcag gccagaagaa gacagtctgt gctgaacctg 2160

atgacccact ctgtgaacca gggccagaac atccacagaa agaccacagc cagcaccaga 2220

aaggtgagcc tggcccccca ggccaacctg acagagctgg acatctacag cagaagactg 2280

agccaggaga caggcctgga gatctctgag gagatcaatg aggaggacct gaaggagtgc 2340

ttctttgatg acatggagag catccctgct gtgaccacct ggaacaccta cctgagatac 2400

atcacagtgc acaagagcct gatctttgtg ctgatctggt gcctggtgat cttcctggct 2460

gaggtggctg ccagcctggt ggtgctgtgg ctgctgggca acacccccct gcaggacaag 2520

ggcaacagca cccacagcag aaacaacagc tatgctgtga tcatcaccag caccagcagc 2580

tactatgtgt tctacatcta tgtgggggtg gctgacaccc tgctggccat gggcttcttc 2640

agaggcctgc ccctggtgca caccctgatc acagtgagca agatcctgca ccacaagatg 2700

ctgcactctg tgctgcaggc ccccatgagc accctgaaca ccctgaaggc tgggggcatc 2760

ctgaacagat tcagcaagga cattgccatc ctggatgacc tgctgcccct gaccatcttt 2820

gacttcatcc agctgctgct gattgtgatt ggggccattg ctgtggtggc tgtgctgcag 2880

ccctacatct ttgtggccac agtgcctgtg attgtggcct tcatcatgct gagagcctac 2940

ttcctgcaga ccagccagca gctgaagcag ctggagtctg agggcagaag ccccatcttc 3000

acccacctgg tgaccagcct gaagggcctg tggaccctga gagcctttgg cagacagccc 3060

tactttgaga ccctgttcca caaggccctg aacctgcaca cagccaactg gttcctgtac 3120

ctgagcaccc tgagatggtt ccagatgaga attgagatga tctttgtgat cttcttcatt 3180

gctgtgacct tcatcagcat cctgaccaca ggggaggggg agggcagagt gggcatcatc 3240

ctgaccctgg ccatgaacat catgagcacc ctgcagtggg ctgtgaacag cagcattgat 3300

gtggacagcc tgatgagatc tgtgagcaga gtgttcaagt tcattgacat gcccacagag 3360

ggcaagccca ccaagagcac caagccctac aagaatggcc agctgagcaa ggtgatgatc 3420

attgagaaca gccatgtgaa gaaggatgac atctggccct ctgggggcca gatgacagtg 3480

aaggacctga cagccaagta cacagagggg ggcaatgcca tcctggagaa catcagcttc 3540

agcatcagcc ctggccagag agtgggcctg ctgggcagaa caggctctgg caagagcacc 3600

ctgctgtctg ccttcctgag actgctgaac acagaggggg agatccagat tgatggggtg 3660

agctgggaca gcatcaccct gcagcagtgg agaaaggcct ttggggtgat cccccagaag 3720

gtgttcatct tctctggcac cttcagaaag aacctggacc cctatgagca gtggtctgac 3780

caggagatct ggaaggtggc tgatgaggtg ggcctgagat ctgtgattga gcagttccct 3840

ggcaagctgg actttgtgct ggtggatggg ggctgtgtgc tgagccatgg ccacaagcag 3900

ctgatgtgcc tggccagatc tgtgctgagc aaggccaaga tcctgctgct ggatgagccc 3960

tctgcccacc tggaccctgt gacctaccag atcatcagaa gaaccctgaa gcaggccttt 4020

gctgactgca cagtgatcct gtgtgagcac agaattgagg ccatgctgga gtgccagcag 4080

ttcctggtga ttgaggagaa caaggtgaga cagtatgaca gcatccagaa gctgctgaat 4140

gagagaagcc tgttcagaca ggccatcagc ccctctgaca gagtgaagct gttcccccac 4200

agaaacagca gcaagtgcaa gagcaagccc cagattgctg ccctgaagga ggagaccgag 4260

gaggaggtgc aggacaccag actgtaa 4287

<210> 133

<211> 4443

<212> DNA

<213> 人工序列

<220>

<223> 密码子优化的，全长囊性纤维化跨膜

调节蛋白 (CFTR)

<400> 133

atgcagagaa gccccctgga gaaggcctct gtggtgagca agctgttctt cagctggacc 60

agacccatcc tgagaaaggg ctacagacag agactggagc tgtctgacat ctaccagatc 120

ccctctgtgg actctgctga caacctgtct gagaagctgg agagagagtg ggacagagag 180

ctggccagca agaagaaccc caagctgatc aatgccctga gaagatgctt cttctggaga 240

ttcatgttct atggcatctt cctgtacctg ggggaggtga ccaaggctgt gcagcccctg 300

ctgctgggca gaatcattgc cagctatgac cctgacaaca aggaggagag aagcattgcc 360

atctacctgg gcattggcct gtgcctgctg ttcattgtga gaaccctgct gctgcaccct 420

gccatctttg gcctgcacca cattggcatg cagatgagaa ttgccatgtt cagcctgatc 480

tacaagaaga ccctgaagct gagcagcaga gtgctggaca agatcagcat tggccagctg 540

gtgagcctgc tgagcaacaa cctgaacaag tttgatgagg gcctggccct ggcccacttt 600

gtgtggattg cccccctgca ggtggccctg ctgatgggcc tgatctggga gctgctgcag 660

gcctctgcct tctgtggcct gggcttcctg attgtgctgg ccctgttcca ggctggcctg 720

ggcagaatga tgatgaagta cagagaccag agagctggca agatctctga gagactggtg 780

atcacctctg agatgattga gaacatccag tctgtgaagg cctactgctg ggaggaggcc 840

atggagaaga tgattgagaa cctgagacag acagagctga agctgaccag aaaggctgcc 900

tatgtgagat acttcaacag ctctgccttc ttcttctctg gcttctttgt ggtgttcctg 960

tctgtgctgc cctatgccct gatcaagggc atcatcctga gaaagatctt caccaccatc 1020

agcttctgca ttgtgctgag aatggctgtg accagacagt tcccctgggc tgtgcagacc 1080

tggtatgaca gcctgggggc catcaacaag atccaggact tcctgcagaa gcaggagtac 1140

aagaccctgg agtacaacct gaccaccaca gaggtggtga tggagaatgt gacagccttc 1200

tgggaggagg gctttgggga gctgtttgag aaggccaagc agaacaacaa caacagaaag 1260

accagcaatg gggatgacag cctgttcttc agcaacttca gcctgctggg cacccctgtg 1320

ctgaaggaca tcaacttcaa gattgagaga ggccagctgc tggctgtggc tggcagcaca 1380

ggggctggca agaccagcct gctgatgatg atcatggggg agctggagcc ctctgagggc 1440

aagatcaagc actctggcag aatcagcttc tgcagccagt tcagctggat catgcctggc 1500

accatcaagg agaacatcat ctttggggtg agctatgatg agtacagata cagatctgtg 1560

atcaaggcct gccagctgga ggaggacatc agcaagtttg ctgagaagga caacattgtg 1620

ctgggggagg ggggcatcac cctgtctggg ggccagagag ccagaatcag cctggccaga 1680

gctgtgtaca aggatgctga cctgtacctg ctggacagcc cctttggcta cctggatgtg 1740

ctgacagaga aggagatctt tgagagctgt gtgtgcaagc tgatggccaa caagaccaga 1800

atcctggtga ccagcaagat ggagcacctg aagaaggctg acaagatcct gatcctgcat 1860

gagggcagca gctacttcta tggcaccttc tctgagctgc agaacctgca gcctgacttc 1920

agcagcaagc tgatgggctg tgacagcttt gaccagttct ctgctgagag aagaaacagc 1980

atcctgacag agaccctgca cagattcagc ctggaggggg atgcccctgt gagctggaca 2040

gagaccaaga agcagagctt caagcagaca ggggagtttg gggagaagag aaagaacagc 2100

atcctgaacc ccatcaacag catcagaaag ttcagcattg tgcagaagac ccccctgcag 2160

atgaatggca ttgaggagga ctctgatgag cccctggaga gaagactgag cctggtgcct 2220

gactctgagc agggggaggc catcctgccc agaatctctg tgatcagcac aggccccacc 2280

ctgcaggcca gaagaagaca gtctgtgctg aacctgatga cccactctgt gaaccagggc 2340

cagaacatcc acagaaagac cacagccagc accagaaagg tgagcctggc cccccaggcc 2400

aacctgacag agctggacat ctacagcaga agactgagcc aggagacagg cctggagatc 2460

tctgaggaga tcaatgagga ggacctgaag gagtgcttct ttgatgacat ggagagcatc 2520

cctgctgtga ccacctggaa cacctacctg agatacatca cagtgcacaa gagcctgatc 2580

tttgtgctga tctggtgcct ggtgatcttc ctggctgagg tggctgccag cctggtggtg 2640

ctgtggctgc tgggcaacac ccccctgcag gacaagggca acagcaccca cagcagaaac 2700

aacagctatg ctgtgatcat caccagcacc agcagctact atgtgttcta catctatgtg 2760

ggggtggctg acaccctgct ggccatgggc ttcttcagag gcctgcccct ggtgcacacc 2820

ctgatcacag tgagcaagat cctgcaccac aagatgctgc actctgtgct gcaggccccc 2880

atgagcaccc tgaacaccct gaaggctggg ggcatcctga acagattcag caaggacatt 2940

gccatcctgg atgacctgct gcccctgacc atctttgact tcatccagct gctgctgatt 3000

gtgattgggg ccattgctgt ggtggctgtg ctgcagccct acatctttgt ggccacagtg 3060

cctgtgattg tggccttcat catgctgaga gcctacttcc tgcagaccag ccagcagctg 3120

aagcagctgg agtctgaggg cagaagcccc atcttcaccc acctggtgac cagcctgaag 3180

ggcctgtgga ccctgagagc ctttggcaga cagccctact ttgagaccct gttccacaag 3240

gccctgaacc tgcacacagc caactggttc ctgtacctga gcaccctgag atggttccag 3300

atgagaattg agatgatctt tgtgatcttc ttcattgctg tgaccttcat cagcatcctg 3360

accacagggg agggggaggg cagagtgggc atcatcctga ccctggccat gaacatcatg 3420

agcaccctgc agtgggctgt gaacagcagc attgatgtgg acagcctgat gagatctgtg 3480

agcagagtgt tcaagttcat tgacatgccc acagagggca agcccaccaa gagcaccaag 3540

ccctacaaga atggccagct gagcaaggtg atgatcattg agaacagcca tgtgaagaag 3600

gatgacatct ggccctctgg gggccagatg acagtgaagg acctgacagc caagtacaca 3660

gaggggggca atgccatcct ggagaacatc agcttcagca tcagccctgg ccagagagtg 3720

ggcctgctgg gcagaacagg ctctggcaag agcaccctgc tgtctgcctt cctgagactg 3780

ctgaacacag agggggagat ccagattgat ggggtgagct gggacagcat caccctgcag 3840

cagtggagaa aggcctttgg ggtgatcccc cagaaggtgt tcatcttctc tggcaccttc 3900

agaaagaacc tggaccccta tgagcagtgg tctgaccagg agatctggaa ggtggctgat 3960

gaggtgggcc tgagatctgt gattgagcag ttccctggca agctggactt tgtgctggtg 4020

gatgggggct gtgtgctgag ccatggccac aagcagctga tgtgcctggc cagatctgtg 4080

ctgagcaagg ccaagatcct gctgctggat gagccctctg cccacctgga ccctgtgacc 4140

taccagatca tcagaagaac cctgaagcag gcctttgctg actgcacagt gatcctgtgt 4200

gagcacagaa ttgaggccat gctggagtgc cagcagttcc tggtgattga ggagaacaag 4260

gtgagacagt atgacagcat ccagaagctg ctgaatgaga gaagcctgtt cagacaggcc 4320

atcagcccct ctgacagagt gaagctgttc ccccacagaa acagcagcaa gtgcaagagc 4380

aagccccaga ttgctgccct gaaggaggag accgaggagg aggtgcagga caccagactg 4440

taa 4443

<210> 134

<211> 502

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(502)

<223> 磺基葡糖胺磺基水解酶 (SGSH)

<400> 134

Met Ser Cys Pro Val Pro Ala Cys Cys Ala Leu Leu Leu Val Leu Gly

1 5 10 15

Leu Cys Arg Ala Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp

20 25 30

Gly Gly Phe Glu Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro

35 40 45

His Leu Asp Ala Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe

50 55 60

Thr Ser Val Ser Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly

65 70 75 80

Leu Pro Gln His Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His

85 90 95

His Phe Asn Ser Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser

100 105 110

Gln Ala Gly Val Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro

115 120 125

Glu Thr Val Tyr Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser

130 135 140

Val Leu Gln Val Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg

145 150 155 160

Lys Phe Leu Gln Thr Gln Asp Asp Gln Pro Phe Phe Leu Tyr Val Ala

165 170 175

Phe His Asp Pro His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr

180 185 190

Phe Cys Glu Lys Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro

195 200 205

Asp Trp Thr Pro Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr

210 215 220

Phe Val Pro Asn Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr

225 230 235 240

Thr Thr Val Gly Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu

245 250 255

Leu Arg Asp Ala Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser

260 265 270

Asp Asn Gly Ile Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro

275 280 285

Gly Thr Ala Glu Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg

290 295 300

Trp Gly Gln Val Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro

305 310 315 320

Thr Ile Leu Asp Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe

325 330 335

Gly Ser Lys Thr Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu

340 345 350

Glu Ala Glu Pro Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His

355 360 365

Glu Val Thr Met Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe

370 375 380

Arg Leu Val His Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln

385 390 395 400

Asp Phe Tyr Val Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr

405 410 415

Ala Gly Gln Pro Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr

420 425 430

Arg Ala Arg Trp Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr

435 440 445

Gln Asn Leu Ala Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu

450 455 460

Arg Asp Gln Leu Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val

465 470 475 480

Cys Ala Pro Asp Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln

485 490 495

Pro Leu His Asn Glu Leu

500

<210> 135

<211> 531

<212> PRT

<213> 人工序列

<220>

<223> 密码子优化的+ GET CO1-SGSH-GET

<400> 135

Met Ser Cys Pro Val Pro Ala Cys Cys Ala Leu Leu Leu Val Leu Gly

1 5 10 15

Leu Cys Arg Ala Arg Pro Arg Asn Ala Leu Leu Leu Leu Ala Asp Asp

20 25 30

Gly Gly Phe Glu Ser Gly Ala Tyr Asn Asn Ser Ala Ile Ala Thr Pro

35 40 45

His Leu Asp Ala Leu Ala Arg Arg Ser Leu Leu Phe Arg Asn Ala Phe

50 55 60

Thr Ser Val Ser Ser Cys Ser Pro Ser Arg Ala Ser Leu Leu Thr Gly

65 70 75 80

Leu Pro Gln His Gln Asn Gly Met Tyr Gly Leu His Gln Asp Val His

85 90 95

His Phe Asn Ser Phe Asp Lys Val Arg Ser Leu Pro Leu Leu Leu Ser

100 105 110

Gln Ala Gly Val Arg Thr Gly Ile Ile Gly Lys Lys His Val Gly Pro

115 120 125

Glu Thr Val Tyr Pro Phe Asp Phe Ala Tyr Thr Glu Glu Asn Gly Ser

130 135 140

Val Leu Gln Val Gly Arg Asn Ile Thr Arg Ile Lys Leu Leu Val Arg

145 150 155 160

Lys Phe Leu Gln Thr Gln Asp Asp Gln Pro Phe Phe Leu Tyr Val Ala

165 170 175

Phe His Asp Pro His Arg Cys Gly His Ser Gln Pro Gln Tyr Gly Thr

180 185 190

Phe Cys Glu Lys Phe Gly Asn Gly Glu Ser Gly Met Gly Arg Ile Pro

195 200 205

Asp Trp Thr Pro Gln Ala Tyr Asp Pro Leu Asp Val Leu Val Pro Tyr

210 215 220

Phe Val Pro Asn Thr Pro Ala Ala Arg Ala Asp Leu Ala Ala Gln Tyr

225 230 235 240

Thr Thr Val Gly Arg Met Asp Gln Gly Val Gly Leu Val Leu Gln Glu

245 250 255

Leu Arg Asp Ala Gly Val Leu Asn Asp Thr Leu Val Ile Phe Thr Ser

260 265 270

Asp Asn Gly Ile Pro Phe Pro Ser Gly Arg Thr Asn Leu Tyr Trp Pro

275 280 285

Gly Thr Ala Glu Pro Leu Leu Val Ser Ser Pro Glu His Pro Lys Arg

290 295 300

Trp Gly Gln Val Ser Glu Ala Tyr Val Ser Leu Leu Asp Leu Thr Pro

305 310 315 320

Thr Ile Leu Asp Trp Phe Ser Ile Pro Tyr Pro Ser Tyr Ala Ile Phe

325 330 335

Gly Ser Lys Thr Ile His Leu Thr Gly Arg Ser Leu Leu Pro Ala Leu

340 345 350

Glu Ala Glu Pro Leu Trp Ala Thr Val Phe Gly Ser Gln Ser His His

355 360 365

Glu Val Thr Met Ser Tyr Pro Met Arg Ser Val Gln His Arg His Phe

370 375 380

Arg Leu Val His Asn Leu Asn Phe Lys Met Pro Phe Pro Ile Asp Gln

385 390 395 400

Asp Phe Tyr Val Ser Pro Thr Phe Gln Asp Leu Leu Asn Arg Thr Thr

405 410 415

Ala Gly Gln Pro Thr Gly Trp Tyr Lys Asp Leu Arg His Tyr Tyr Tyr

420 425 430

Arg Ala Arg Trp Glu Leu Tyr Asp Arg Ser Arg Asp Pro His Glu Thr

435 440 445

Gln Asn Leu Ala Thr Asp Pro Arg Phe Ala Gln Leu Leu Glu Met Leu

450 455 460

Arg Asp Gln Leu Ala Lys Trp Gln Trp Glu Thr His Asp Pro Trp Val

465 470 475 480

Cys Ala Pro Asp Gly Val Leu Glu Glu Lys Leu Ser Pro Gln Cys Gln

485 490 495

Pro Leu His Asn Glu Leu Arg Arg Arg Arg Arg Arg Arg Arg Lys Arg

500 505 510

Lys Lys Lys Gly Lys Gly Leu Gly Lys Lys Arg Asp Pro Cys Leu Arg

515 520 525

Lys Tyr Lys

530

<210> 136

<211> 306

<212> PRT

<213> 人工序列

<220>

<223> 密码子优化的蜡样质脂褐质沉积症神经元蛋白1 (CLN1)

<400> 136

Met Ala Ser Pro Gly Cys Leu Trp Leu Leu Ala Val Ala Leu Leu Pro

1 5 10 15

Trp Thr Cys Ala Ser Arg Ala Leu Gln His Leu Asp Pro Pro Ala Pro

20 25 30

Leu Pro Leu Val Ile Trp His Gly Met Gly Asp Ser Cys Cys Asn Pro

35 40 45

Leu Ser Met Gly Ala Ile Lys Lys Met Val Glu Lys Lys Ile Pro Gly

50 55 60

Ile Tyr Val Leu Ser Leu Glu Ile Gly Lys Thr Leu Met Glu Asp Val

65 70 75 80

Glu Asn Ser Phe Phe Leu Asn Val Asn Ser Gln Val Thr Thr Val Cys

85 90 95

Gln Ala Leu Ala Lys Asp Pro Lys Leu Gln Gln Gly Tyr Asn Ala Met

100 105 110

Gly Phe Ser Gln Gly Gly Gln Phe Leu Arg Ala Val Ala Gln Arg Cys

115 120 125

Pro Ser Pro Pro Met Ile Asn Leu Ile Ser Val Gly Gly Gln His Gln

130 135 140

Gly Val Phe Gly Leu Pro Arg Cys Pro Gly Glu Ser Ser His Ile Cys

145 150 155 160

Asp Phe Ile Arg Lys Thr Leu Asn Ala Gly Ala Tyr Ser Lys Val Val

165 170 175

Gln Glu Arg Leu Val Gln Ala Glu Tyr Trp His Asp Pro Ile Lys Glu

180 185 190

Asp Val Tyr Arg Asn His Ser Ile Phe Leu Ala Asp Ile Asn Gln Glu

195 200 205

Arg Gly Ile Asn Glu Ser Tyr Lys Lys Asn Leu Met Ala Leu Lys Lys

210 215 220

Phe Val Met Val Lys Phe Leu Asn Asp Ser Ile Val Asp Pro Val Asp

225 230 235 240

Ser Glu Trp Phe Gly Phe Tyr Arg Ser Gly Gln Ala Lys Glu Thr Ile

245 250 255

Pro Leu Gln Glu Thr Ser Leu Tyr Thr Gln Asp Arg Leu Gly Leu Lys

260 265 270

Glu Met Asp Asn Ala Gly Gln Leu Val Phe Leu Ala Thr Glu Gly Asp

275 280 285

His Leu Gln Leu Ser Glu Glu Trp Phe Tyr Ala His Ile Ile Pro Phe

290 295 300

Leu Gly

305

<210> 137

<211> 294

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(294)

<223> 运动神经元生存蛋白1 (SMN1)

<400> 137

Met Ala Met Ser Ser Gly Gly Ser Gly Gly Gly Val Pro Glu Gln Glu

1 5 10 15

Asp Ser Val Leu Phe Arg Arg Gly Thr Gly Gln Ser Asp Asp Ser Asp

20 25 30

Ile Trp Asp Asp Thr Ala Leu Ile Lys Ala Tyr Asp Lys Ala Val Ala

35 40 45

Ser Phe Lys His Ala Leu Lys Asn Gly Asp Ile Cys Glu Thr Ser Gly

50 55 60

Lys Pro Lys Thr Thr Pro Lys Arg Lys Pro Ala Lys Lys Asn Lys Ser

65 70 75 80

Gln Lys Lys Asn Thr Ala Ala Ser Leu Gln Gln Trp Lys Val Gly Asp

85 90 95

Lys Cys Ser Ala Ile Trp Ser Glu Asp Gly Cys Ile Tyr Pro Ala Thr

100 105 110

Ile Ala Ser Ile Asp Phe Lys Arg Glu Thr Cys Val Val Val Tyr Thr

115 120 125

Gly Tyr Gly Asn Arg Glu Glu Gln Asn Leu Ser Asp Leu Leu Ser Pro

130 135 140

Ile Cys Glu Val Ala Asn Asn Ile Glu Gln Asn Ala Gln Glu Asn Glu

145 150 155 160

Asn Glu Ser Gln Val Ser Thr Asp Glu Ser Glu Asn Ser Arg Ser Pro

165 170 175

Gly Asn Lys Ser Asp Asn Ile Lys Pro Lys Ser Ala Pro Trp Asn Ser

180 185 190

Phe Leu Pro Pro Pro Pro Pro Met Pro Gly Pro Arg Leu Gly Pro Gly

195 200 205

Lys Pro Gly Leu Lys Phe Asn Gly Pro Pro Pro Pro Pro Pro Pro Pro

210 215 220

Pro Pro His Leu Leu Ser Cys Trp Leu Pro Pro Phe Pro Ser Gly Pro

225 230 235 240

Pro Ile Ile Pro Pro Pro Pro Pro Ile Cys Pro Asp Ser Leu Asp Asp

245 250 255

Ala Asp Ala Leu Gly Ser Met Leu Ile Ser Trp Tyr Met Ser Gly Tyr

260 265 270

His Thr Gly Tyr Tyr Met Gly Phe Arg Gln Asn Gln Lys Glu Gly Arg

275 280 285

Cys Ser His Ser Leu Asn

290

<210> 138

<211> 515

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(515)

<223> 组织非特异性碱性磷酸酶 (TNALP)

<400> 138

Met Ile Ser Pro Phe Leu Val Leu Ala Ile Gly Thr Cys Leu Thr Asn

1 5 10 15

Ser Leu Val Pro Glu Lys Glu Lys Asp Pro Lys Tyr Trp Arg Asp Gln

20 25 30

Ala Gln Glu Thr Leu Lys Tyr Ala Leu Glu Leu Gln Lys Leu Asn Thr

35 40 45

Asn Val Ala Lys Asn Val Ile Met Phe Leu Gly Asp Gly Met Gly Val

50 55 60

Ser Thr Val Thr Ala Ala Arg Ile Leu Lys Gly Gln Leu His His Asn

65 70 75 80

Pro Gly Glu Glu Thr Arg Leu Glu Met Asp Lys Phe Pro Phe Val Ala

85 90 95

Leu Ser Lys Thr Tyr Asn Thr Asn Ala Gln Val Pro Asp Ser Ala Gly

100 105 110

Thr Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Glu Gly Thr Val

115 120 125

Gly Val Ser Ala Ala Thr Glu Arg Ser Arg Cys Asn Thr Thr Gln Gly

130 135 140

Asn Glu Val Thr Ser Ile Leu Arg Trp Ala Lys Asp Ala Gly Lys Ser

145 150 155 160

Val Gly Ile Val Thr Thr Thr Arg Val Asn His Ala Thr Pro Ser Ala

165 170 175

Ala Tyr Ala His Ser Ala Asp Arg Asp Trp Tyr Ser Asp Asn Glu Met

180 185 190

Pro Pro Glu Ala Leu Ser Gln Gly Cys Lys Asp Ile Ala Tyr Gln Leu

195 200 205

Met His Asn Ile Arg Asp Ile Asp Val Ile Met Gly Gly Gly Arg Lys

210 215 220

Tyr Met Tyr Pro Lys Asn Lys Thr Asp Val Glu Tyr Glu Ser Asp Glu

225 230 235 240

Lys Ala Arg Gly Thr Arg Leu Asp Gly Leu Asp Leu Val Asp Thr Trp

245 250 255

Lys Ser Phe Lys Pro Arg Tyr Lys His Ser His Phe Ile Trp Asn Arg

260 265 270

Thr Glu Leu Leu Thr Leu Asp Pro His Asn Val Asp Tyr Leu Leu Gly

275 280 285

Leu Phe Glu Pro Gly Asp Met Gln Tyr Glu Leu Asn Arg Asn Asn Val

290 295 300

Thr Asp Pro Ser Leu Ser Glu Met Val Val Val Ala Ile Gln Ile Leu

305 310 315 320

Arg Lys Asn Pro Lys Gly Phe Phe Leu Leu Val Glu Gly Gly Arg Ile

325 330 335

Asp His Gly His His Glu Gly Lys Ala Lys Gln Ala Leu His Glu Ala

340 345 350

Val Glu Met Asp Arg Ala Ile Gly Gln Ala Gly Ser Leu Thr Ser Ser

355 360 365

Glu Asp Thr Leu Thr Val Val Thr Ala Asp His Ser His Val Phe Thr

370 375 380

Phe Gly Gly Tyr Thr Pro Arg Gly Asn Ser Ile Phe Gly Leu Ala Pro

385 390 395 400

Met Leu Ser Asp Thr Asp Lys Lys Pro Phe Thr Ala Ile Leu Tyr Gly

405 410 415

Asn Gly Pro Gly Tyr Lys Val Val Gly Gly Glu Arg Glu Asn Val Ser

420 425 430

Met Val Asp Tyr Ala His Asn Asn Tyr Gln Ala Gln Ser Ala Val Pro

435 440 445

Leu Arg His Glu Thr His Gly Gly Glu Asp Val Ala Val Phe Ser Lys

450 455 460

Gly Pro Met Ala His Leu Leu His Gly Val His Glu Gln Asn Tyr Val

465 470 475 480

Pro His Val Met Ala Tyr Ala Ala Cys Ile Gly Ala Asn Leu Gly His

485 490 495

Cys Ala Pro Ala Ser Ser Ala Gly Ser Asp Asp Asp Asp Asp Asp Asp

500 505 510

Asp Asp Asp

515

<210> 139

<211> 211

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(211)

<223> 神经胶质细胞源性神经营养因子 (GDNF)

<400> 139

Met Lys Leu Trp Asp Val Val Ala Val Cys Leu Val Leu Leu His Thr

1 5 10 15

Ala Ser Ala Phe Pro Leu Pro Ala Gly Lys Arg Pro Pro Glu Ala Pro

20 25 30

Ala Glu Asp Arg Ser Leu Gly Arg Arg Arg Ala Pro Phe Ala Leu Ser

35 40 45

Ser Asp Ser Asn Met Pro Glu Asp Tyr Pro Asp Gln Phe Asp Asp Val

50 55 60

Met Asp Phe Ile Gln Ala Thr Ile Lys Arg Leu Lys Arg Ser Pro Asp

65 70 75 80

Lys Gln Met Ala Val Leu Pro Arg Arg Glu Arg Asn Arg Gln Ala Ala

85 90 95

Ala Ala Asn Pro Glu Asn Ser Arg Gly Lys Gly Arg Arg Gly Gln Arg

100 105 110

Gly Lys Asn Arg Gly Cys Val Leu Thr Ala Ile His Leu Asn Val Thr

115 120 125

Asp Leu Gly Leu Gly Tyr Glu Thr Lys Glu Glu Leu Ile Phe Arg Tyr

130 135 140

Cys Ser Gly Ser Cys Asp Ala Ala Glu Thr Thr Tyr Asp Lys Ile Leu

145 150 155 160

Lys Asn Leu Ser Arg Asn Arg Arg Leu Val Ser Asp Lys Val Gly Gln

165 170 175

Ala Cys Cys Arg Pro Ile Ala Phe Asp Asp Asp Leu Ser Phe Leu Asp

180 185 190

Asp Asn Leu Val Tyr His Ile Leu Arg Lys His Ser Ala Lys Arg Cys

195 200 205

Gly Cys Ile

210

<210> 140

<211> 536

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(536)

<223> 组织葡糖基神经酰胺酶β (GBA1)

<400> 140

Met Glu Phe Ser Ser Pro Ser Arg Glu Glu Cys Pro Lys Pro Leu Ser

1 5 10 15

Arg Val Ser Ile Met Ala Gly Ser Leu Thr Gly Leu Leu Leu Leu Gln

20 25 30

Ala Val Ser Trp Ala Ser Gly Ala Arg Pro Cys Ile Pro Lys Ser Phe

35 40 45

Gly Tyr Ser Ser Val Val Cys Val Cys Asn Ala Thr Tyr Cys Asp Ser

50 55 60

Phe Asp Pro Pro Thr Phe Pro Ala Leu Gly Thr Phe Ser Arg Tyr Glu

65 70 75 80

Ser Thr Arg Ser Gly Arg Arg Met Glu Leu Ser Met Gly Pro Ile Gln

85 90 95

Ala Asn His Thr Gly Thr Gly Leu Leu Leu Thr Leu Gln Pro Glu Gln

100 105 110

Lys Phe Gln Lys Val Lys Gly Phe Gly Gly Ala Met Thr Asp Ala Ala

115 120 125

Ala Leu Asn Ile Leu Ala Leu Ser Pro Pro Ala Gln Asn Leu Leu Leu

130 135 140

Lys Ser Tyr Phe Ser Glu Glu Gly Ile Gly Tyr Asn Ile Ile Arg Val

145 150 155 160

Pro Met Ala Ser Cys Asp Phe Ser Ile Arg Thr Tyr Thr Tyr Ala Asp

165 170 175

Thr Pro Asp Asp Phe Gln Leu His Asn Phe Ser Leu Pro Glu Glu Asp

180 185 190

Thr Lys Leu Lys Ile Pro Leu Ile His Arg Ala Leu Gln Leu Ala Gln

195 200 205

Arg Pro Val Ser Leu Leu Ala Ser Pro Trp Thr Ser Pro Thr Trp Leu

210 215 220

Lys Thr Asn Gly Ala Val Asn Gly Lys Gly Ser Leu Lys Gly Gln Pro

225 230 235 240

Gly Asp Ile Tyr His Gln Thr Trp Ala Arg Tyr Phe Val Lys Phe Leu

245 250 255

Asp Ala Tyr Ala Glu His Lys Leu Gln Phe Trp Ala Val Thr Ala Glu

260 265 270

Asn Glu Pro Ser Ala Gly Leu Leu Ser Gly Tyr Pro Phe Gln Cys Leu

275 280 285

Gly Phe Thr Pro Glu His Gln Arg Asp Phe Ile Ala Arg Asp Leu Gly

290 295 300

Pro Thr Leu Ala Asn Ser Thr His His Asn Val Arg Leu Leu Met Leu

305 310 315 320

Asp Asp Gln Arg Leu Leu Leu Pro His Trp Ala Lys Val Val Leu Thr

325 330 335

Asp Pro Glu Ala Ala Lys Tyr Val His Gly Ile Ala Val His Trp Tyr

340 345 350

Leu Asp Phe Leu Ala Pro Ala Lys Ala Thr Leu Gly Glu Thr His Arg

355 360 365

Leu Phe Pro Asn Thr Met Leu Phe Ala Ser Glu Ala Cys Val Gly Ser

370 375 380

Lys Phe Trp Glu Gln Ser Val Arg Leu Gly Ser Trp Asp Arg Gly Met

385 390 395 400

Gln Tyr Ser His Ser Ile Ile Thr Asn Leu Leu Tyr His Val Val Gly

405 410 415

Trp Thr Asp Trp Asn Leu Ala Leu Asn Pro Glu Gly Gly Pro Asn Trp

420 425 430

Val Arg Asn Phe Val Asp Ser Pro Ile Ile Val Asp Ile Thr Lys Asp

435 440 445

Thr Phe Tyr Lys Gln Pro Met Phe Tyr His Leu Gly His Phe Ser Lys

450 455 460

Phe Ile Pro Glu Gly Ser Gln Arg Val Gly Leu Val Ala Ser Gln Lys

465 470 475 480

Asn Asp Leu Asp Ala Val Ala Leu Met His Pro Asp Gly Ser Ala Val

485 490 495

Val Val Val Leu Asn Arg Ser Ser Lys Asp Val Pro Leu Thr Ile Lys

500 505 510

Asp Pro Ala Val Gly Phe Leu Glu Thr Ile Ser Pro Gly Tyr Ser Ile

515 520 525

His Thr Tyr Leu Trp Arg Arg Gln

530 535

<210> 141

<211> 653

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(653)

<223> 艾杜糖苷酸酶α-L- (IDUA)

<400> 141

Met Arg Pro Leu Arg Pro Arg Ala Ala Leu Leu Ala Leu Leu Ala Ser

1 5 10 15

Leu Leu Ala Ala Pro Pro Val Ala Pro Ala Glu Ala Pro His Leu Val

20 25 30

His Val Asp Ala Ala Arg Ala Leu Trp Pro Leu Arg Arg Phe Trp Arg

35 40 45

Ser Thr Gly Phe Cys Pro Pro Leu Pro His Ser Gln Ala Asp Gln Tyr

50 55 60

Val Leu Ser Trp Asp Gln Gln Leu Asn Leu Ala Tyr Val Gly Ala Val

65 70 75 80

Pro His Arg Gly Ile Lys Gln Val Arg Thr His Trp Leu Leu Glu Leu

85 90 95

Val Thr Thr Arg Gly Ser Thr Gly Arg Gly Leu Ser Tyr Asn Phe Thr

100 105 110

His Leu Asp Gly Tyr Leu Asp Leu Leu Arg Glu Asn Gln Leu Leu Pro

115 120 125

Gly Phe Glu Leu Met Gly Ser Ala Ser Gly His Phe Thr Asp Phe Glu

130 135 140

Asp Lys Gln Gln Val Phe Glu Trp Lys Asp Leu Val Ser Ser Leu Ala

145 150 155 160

Arg Arg Tyr Ile Gly Arg Tyr Gly Leu Ala His Val Ser Lys Trp Asn

165 170 175

Phe Glu Thr Trp Asn Glu Pro Asp His His Asp Phe Asp Asn Val Ser

180 185 190

Met Thr Met Gln Gly Phe Leu Asn Tyr Tyr Asp Ala Cys Ser Glu Gly

195 200 205

Leu Arg Ala Ala Ser Pro Ala Leu Arg Leu Gly Gly Pro Gly Asp Ser

210 215 220

Phe His Thr Pro Pro Arg Ser Pro Leu Ser Trp Gly Leu Leu Arg His

225 230 235 240

Cys His Asp Gly Thr Asn Phe Phe Thr Gly Glu Ala Gly Val Arg Leu

245 250 255

Asp Tyr Ile Ser Leu His Arg Lys Gly Ala Arg Ser Ser Ile Ser Ile

260 265 270

Leu Glu Gln Glu Lys Val Val Ala Gln Gln Ile Arg Gln Leu Phe Pro

275 280 285

Lys Phe Ala Asp Thr Pro Ile Tyr Asn Asp Glu Ala Asp Pro Leu Val

290 295 300

Gly Trp Ser Leu Pro Gln Pro Trp Arg Ala Asp Val Thr Tyr Ala Ala

305 310 315 320

Met Val Val Lys Val Ile Ala Gln His Gln Asn Leu Leu Leu Ala Asn

325 330 335

Thr Thr Ser Ala Phe Pro Tyr Ala Leu Leu Ser Asn Asp Asn Ala Phe

340 345 350

Leu Ser Tyr His Pro His Pro Phe Ala Gln Arg Thr Leu Thr Ala Arg

355 360 365

Phe Gln Val Asn Asn Thr Arg Pro Pro His Val Gln Leu Leu Arg Lys

370 375 380

Pro Val Leu Thr Ala Met Gly Leu Leu Ala Leu Leu Asp Glu Glu Gln

385 390 395 400

Leu Trp Ala Glu Val Ser Gln Ala Gly Thr Val Leu Asp Ser Asn His

405 410 415

Thr Val Gly Val Leu Ala Ser Ala His Arg Pro Gln Gly Pro Ala Asp

420 425 430

Ala Trp Arg Ala Ala Val Leu Ile Tyr Ala Ser Asp Asp Thr Arg Ala

435 440 445

His Pro Asn Arg Ser Val Ala Val Thr Leu Arg Leu Arg Gly Val Pro

450 455 460

Pro Gly Pro Gly Leu Val Tyr Val Thr Arg Tyr Leu Asp Asn Gly Leu

465 470 475 480

Cys Ser Pro Asp Gly Glu Trp Arg Arg Leu Gly Arg Pro Val Phe Pro

485 490 495

Thr Ala Glu Gln Phe Arg Arg Met Arg Ala Ala Glu Asp Pro Val Ala

500 505 510

Ala Ala Pro Arg Pro Leu Pro Ala Gly Gly Arg Leu Thr Leu Arg Pro

515 520 525

Ala Leu Arg Leu Pro Ser Leu Leu Leu Val His Val Cys Ala Arg Pro

530 535 540

Glu Lys Pro Pro Gly Gln Val Thr Arg Leu Arg Ala Leu Pro Leu Thr

545 550 555 560

Gln Gly Gln Leu Val Leu Val Trp Ser Asp Glu His Val Gly Ser Lys

565 570 575

Cys Leu Trp Thr Tyr Glu Ile Gln Phe Ser Gln Asp Gly Lys Ala Tyr

580 585 590

Thr Pro Val Ser Arg Lys Pro Ser Thr Phe Asn Leu Phe Val Phe Ser

595 600 605

Pro Asp Thr Gly Ala Val Ser Gly Ser Tyr Arg Val Arg Ala Leu Asp

610 615 620

Tyr Trp Ala Arg Pro Gly Pro Phe Ser Asp Pro Val Pro Tyr Leu Glu

625 630 635 640

Val Pro Val Pro Arg Gly Pro Pro Ser Pro Gly Asn Pro

645 650

<210> 142

<211> 525

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(525)

<223> 细胞色素P450家族4亚家族V成员2 (CYP4V2)

<400> 142

Met Ala Gly Leu Trp Leu Gly Leu Val Trp Gln Lys Leu Leu Leu Trp

1 5 10 15

Gly Ala Ala Ser Ala Leu Ser Leu Ala Gly Ala Ser Leu Val Leu Ser

20 25 30

Leu Leu Gln Arg Val Ala Ser Tyr Ala Arg Lys Trp Gln Gln Met Arg

35 40 45

Pro Ile Pro Thr Val Ala Arg Ala Tyr Pro Leu Val Gly His Ala Leu

50 55 60

Leu Met Lys Pro Asp Gly Arg Glu Phe Phe Gln Gln Ile Ile Glu Tyr

65 70 75 80

Thr Glu Glu Tyr Arg His Met Pro Leu Leu Lys Leu Trp Val Gly Pro

85 90 95

Val Pro Met Val Ala Leu Tyr Asn Ala Glu Asn Val Glu Val Ile Leu

100 105 110

Thr Ser Ser Lys Gln Ile Asp Lys Ser Ser Met Tyr Lys Phe Leu Glu

115 120 125

Pro Trp Leu Gly Leu Gly Leu Leu Thr Ser Thr Gly Asn Lys Trp Arg

130 135 140

Ser Arg Arg Lys Met Leu Thr Pro Thr Phe His Phe Thr Ile Leu Glu

145 150 155 160

Asp Phe Leu Asp Ile Met Asn Glu Gln Ala Asn Ile Leu Val Lys Lys

165 170 175

Leu Glu Lys His Ile Asn Gln Glu Ala Phe Asn Cys Phe Phe Tyr Ile

180 185 190

Thr Leu Cys Ala Leu Asp Ile Ile Cys Glu Thr Ala Met Gly Lys Asn

195 200 205

Ile Gly Ala Gln Ser Asn Asp Asp Ser Glu Tyr Val Arg Ala Val Tyr

210 215 220

Arg Met Ser Glu Met Ile Phe Arg Arg Ile Lys Met Pro Trp Leu Trp

225 230 235 240

Leu Asp Leu Trp Tyr Leu Met Phe Lys Glu Gly Trp Glu His Lys Lys

245 250 255

Ser Leu Gln Ile Leu His Thr Phe Thr Asn Ser Val Ile Ala Glu Arg

260 265 270

Ala Asn Glu Met Asn Ala Asn Glu Asp Cys Arg Gly Asp Gly Arg Gly

275 280 285

Ser Ala Pro Ser Lys Asn Lys Arg Arg Ala Phe Leu Asp Leu Leu Leu

290 295 300

Ser Val Thr Asp Asp Glu Gly Asn Arg Leu Ser His Glu Asp Ile Arg

305 310 315 320

Glu Glu Val Asp Thr Phe Met Phe Glu Gly His Asp Thr Thr Ala Ala

325 330 335

Ala Ile Asn Trp Ser Leu Tyr Leu Leu Gly Ser Asn Pro Glu Val Gln

340 345 350

Lys Lys Val Asp His Glu Leu Asp Asp Val Phe Gly Lys Ser Asp Arg

355 360 365

Pro Ala Thr Val Glu Asp Leu Lys Lys Leu Arg Tyr Leu Glu Cys Val

370 375 380

Ile Lys Glu Thr Leu Arg Leu Phe Pro Ser Val Pro Leu Phe Ala Arg

385 390 395 400

Ser Val Ser Glu Asp Cys Glu Val Ala Gly Tyr Arg Val Leu Lys Gly

405 410 415

Thr Glu Ala Val Ile Ile Pro Tyr Ala Leu His Arg Asp Pro Arg Tyr

420 425 430

Phe Pro Asn Pro Glu Glu Phe Gln Pro Glu Arg Phe Phe Pro Glu Asn

435 440 445

Ala Gln Gly Arg His Pro Tyr Ala Tyr Val Pro Phe Ser Ala Gly Pro

450 455 460

Arg Asn Cys Ile Gly Gln Lys Phe Ala Val Met Glu Glu Lys Thr Ile

465 470 475 480

Leu Ser Cys Ile Leu Arg His Phe Trp Ile Glu Ser Asn Gln Lys Arg

485 490 495

Glu Glu Leu Gly Leu Glu Gly Gln Leu Ile Leu Arg Pro Ser Asn Gly

500 505 510

Ile Trp Ile Lys Leu Lys Arg Arg Asn Ala Asp Glu Arg

515 520 525

<210> 143

<211> 236

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(236)

<223> 视网膜劈裂蛋白 1 (RS1)

<400> 143

Met Ser Arg Lys Ile Glu Gly Phe Leu Leu Leu Leu Leu Phe Gly Tyr

1 5 10 15

Glu Ala Thr Leu Gly Leu Ser Ser Thr Glu Asp Glu Gly Glu Asp Pro

20 25 30

Trp Tyr Gln Lys Ala Cys Asp Glu Gly Glu Asp Pro Trp Tyr Gln Lys

35 40 45

Ala Cys Lys Cys Asp Cys Gln Gly Gly Pro Asn Ala Leu Trp Ser Ala

50 55 60

Gly Ala Thr Ser Leu Asp Cys Ile Pro Glu Cys Pro Tyr His Lys Pro

65 70 75 80

Leu Gly Phe Glu Ser Gly Glu Val Thr Pro Asp Gln Ile Thr Cys Ser

85 90 95

Asn Pro Glu Gln Tyr Val Gly Trp Tyr Ser Ser Trp Thr Ala Asn Lys

100 105 110

Ala Arg Leu Asn Ser Gln Gly Phe Gly Cys Ala Trp Leu Ser Lys Phe

115 120 125

Gln Asp Ser Ser Gln Trp Leu Gln Ile Asp Leu Lys Glu Ile Lys Val

130 135 140

Ile Ser Gly Ile Leu Thr Gln Gly Arg Cys Asp Ile Asp Glu Trp Met

145 150 155 160

Thr Lys Tyr Ser Val Gln Tyr Arg Thr Asp Glu Arg Leu Asn Trp Ile

165 170 175

Tyr Tyr Lys Asp Gln Thr Gly Asn Asn Arg Val Phe Tyr Gly Asn Ser

180 185 190

Asp Arg Thr Ser Thr Val Gln Asn Leu Leu Arg Pro Pro Ile Ile Ser

195 200 205

Arg Phe Ile Arg Leu Ile Pro Leu Gly Trp His Val Arg Ile Ala Ile

210 215 220

Arg Met Glu Leu Leu Glu Cys Val Ser Lys Cys Ala

225 230 235

<210> 144

<211> 854

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(854)

<223> 磷酸二酯酶 6B (PDE6B)

<400> 144

Met Ser Leu Ser Glu Glu Gln Ala Arg Ser Phe Leu Asp Gln Asn Pro

1 5 10 15

Asp Phe Ala Arg Gln Tyr Phe Gly Lys Lys Leu Ser Pro Glu Asn Val

20 25 30

Ala Ala Ala Cys Glu Asp Gly Cys Pro Pro Asp Cys Asp Ser Leu Arg

35 40 45

Asp Leu Cys Gln Val Glu Glu Ser Thr Ala Leu Leu Glu Leu Val Gln

50 55 60

Asp Met Gln Glu Ser Ile Asn Met Glu Arg Val Val Phe Lys Val Leu

65 70 75 80

Arg Arg Leu Cys Thr Leu Leu Gln Ala Asp Arg Cys Ser Leu Phe Met

85 90 95

Tyr Arg Gln Arg Asn Gly Val Ala Glu Leu Ala Thr Arg Leu Phe Ser

100 105 110

Val Gln Pro Asp Ser Val Leu Glu Asp Cys Leu Val Pro Pro Asp Ser

115 120 125

Glu Ile Val Phe Pro Leu Asp Ile Gly Val Val Gly His Val Ala Gln

130 135 140

Thr Lys Lys Met Val Asn Val Glu Asp Val Ala Glu Cys Pro His Phe

145 150 155 160

Ser Ser Phe Ala Asp Glu Leu Thr Asp Tyr Lys Thr Lys Asn Met Leu

165 170 175

Ala Thr Pro Ile Met Asn Gly Lys Asp Val Val Ala Val Ile Met Ala

180 185 190

Val Asn Lys Leu Asn Gly Pro Phe Phe Thr Ser Glu Asp Glu Asp Val

195 200 205

Phe Leu Lys Tyr Leu Asn Phe Ala Thr Leu Tyr Leu Lys Ile Tyr His

210 215 220

Leu Ser Tyr Leu His Asn Cys Glu Thr Arg Arg Gly Gln Val Leu Leu

225 230 235 240

Trp Ser Ala Asn Lys Val Phe Glu Glu Leu Thr Asp Ile Glu Arg Gln

245 250 255

Phe His Lys Ala Phe Tyr Thr Val Arg Ala Tyr Leu Asn Cys Glu Arg

260 265 270

Tyr Ser Val Gly Leu Leu Asp Met Thr Lys Glu Lys Glu Phe Phe Asp

275 280 285

Val Trp Ser Val Leu Met Gly Glu Ser Gln Pro Tyr Ser Gly Pro Arg

290 295 300

Thr Pro Asp Gly Arg Glu Ile Val Phe Tyr Lys Val Ile Asp Tyr Ile

305 310 315 320

Leu His Gly Lys Glu Glu Ile Lys Val Ile Pro Thr Pro Ser Ala Asp

325 330 335

His Trp Ala Leu Ala Ser Gly Leu Pro Ser Tyr Val Ala Glu Ser Gly

340 345 350

Phe Ile Cys Asn Ile Met Asn Ala Ser Ala Asp Glu Met Phe Lys Phe

355 360 365

Gln Glu Gly Ala Leu Asp Asp Ser Gly Trp Leu Ile Lys Asn Val Leu

370 375 380

Ser Met Pro Ile Val Asn Lys Lys Glu Glu Ile Val Gly Val Ala Thr

385 390 395 400

Phe Tyr Asn Arg Lys Asp Gly Lys Pro Phe Asp Glu Gln Asp Glu Val

405 410 415

Leu Met Glu Ser Leu Thr Gln Phe Leu Gly Trp Ser Val Met Asn Thr

420 425 430

Asp Thr Tyr Asp Lys Met Asn Lys Leu Glu Asn Arg Lys Asp Ile Ala

435 440 445

Gln Asp Met Val Leu Tyr His Val Lys Cys Asp Arg Asp Glu Ile Gln

450 455 460

Leu Ile Leu Pro Thr Arg Ala Arg Leu Gly Lys Glu Pro Ala Asp Cys

465 470 475 480

Asp Glu Asp Glu Leu Gly Glu Ile Leu Lys Glu Glu Leu Pro Gly Pro

485 490 495

Thr Thr Phe Asp Ile Tyr Glu Phe His Phe Ser Asp Leu Glu Cys Thr

500 505 510

Glu Leu Asp Leu Val Lys Cys Gly Ile Gln Met Tyr Tyr Glu Leu Gly

515 520 525

Val Val Arg Lys Phe Gln Ile Pro Gln Glu Val Leu Val Arg Phe Leu

530 535 540

Phe Ser Ile Ser Lys Gly Tyr Arg Arg Ile Thr Tyr His Asn Trp Arg

545 550 555 560

His Gly Phe Asn Val Ala Gln Thr Met Phe Thr Leu Leu Met Thr Gly

565 570 575

Lys Leu Lys Ser Tyr Tyr Thr Asp Leu Glu Ala Phe Ala Met Val Thr

580 585 590

Ala Gly Leu Cys His Asp Ile Asp His Arg Gly Thr Asn Asn Leu Tyr

595 600 605

Gln Met Lys Ser Gln Asn Pro Leu Ala Lys Leu His Gly Ser Ser Ile

610 615 620

Leu Glu Arg His His Leu Glu Phe Gly Lys Phe Leu Leu Ser Glu Glu

625 630 635 640

Thr Leu Asn Ile Tyr Gln Asn Leu Asn Arg Arg Gln His Glu His Val

645 650 655

Ile His Leu Met Asp Ile Ala Ile Ile Ala Thr Asp Leu Ala Leu Tyr

660 665 670

Phe Lys Lys Arg Ala Met Phe Gln Lys Ile Val Asp Glu Ser Lys Asn

675 680 685

Tyr Gln Asp Lys Lys Ser Trp Val Glu Tyr Leu Ser Leu Glu Thr Thr

690 695 700

Arg Lys Glu Ile Val Met Ala Met Met Met Thr Ala Cys Asp Leu Ser

705 710 715 720

Ala Ile Thr Lys Pro Trp Glu Val Gln Ser Lys Val Ala Leu Leu Val

725 730 735

Ala Ala Glu Phe Trp Glu Gln Gly Asp Leu Glu Arg Thr Val Leu Asp

740 745 750

Gln Gln Pro Ile Pro Met Met Asp Arg Asn Lys Ala Ala Glu Leu Pro

755 760 765

Lys Leu Gln Val Gly Phe Ile Asp Phe Val Cys Thr Phe Val Tyr Lys

770 775 780

Glu Phe Ser Arg Phe His Glu Glu Ile Leu Pro Met Phe Asp Arg Leu

785 790 795 800

Gln Asn Asn Arg Lys Glu Trp Lys Ala Leu Ala Asp Glu Tyr Glu Ala

805 810 815

Lys Val Lys Ala Leu Glu Glu Lys Glu Glu Glu Glu Arg Val Ala Ala

820 825 830

Lys Lys Val Gly Thr Glu Ile Cys Asn Gly Gly Pro Ala Pro Lys Ser

835 840 845

Ser Thr Cys Cys Ile Leu

850

<210> 145

<211> 498

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(498)

<223> 甲基-CpG结合蛋白 (MeCP2)

<400> 145

Met Ala Ala Ala Ala Ala Ala Ala Pro Ser Gly Gly Gly Gly Gly Gly

1 5 10 15

Glu Glu Glu Arg Leu Glu Glu Lys Ser Glu Asp Gln Asp Leu Gln Gly

20 25 30

Leu Lys Asp Lys Pro Leu Lys Phe Lys Lys Val Lys Lys Asp Lys Lys

35 40 45

Glu Glu Lys Glu Gly Lys His Glu Pro Val Gln Pro Ser Ala His His

50 55 60

Ser Ala Glu Pro Ala Glu Ala Gly Lys Ala Glu Thr Ser Glu Gly Ser

65 70 75 80

Gly Ser Ala Pro Ala Val Pro Glu Ala Ser Ala Ser Pro Lys Gln Arg

85 90 95

Arg Ser Ile Ile Arg Asp Arg Gly Pro Met Tyr Asp Asp Pro Thr Leu

100 105 110

Pro Glu Gly Trp Thr Arg Lys Leu Lys Gln Arg Lys Ser Gly Arg Ser

115 120 125

Ala Gly Lys Tyr Asp Val Tyr Leu Ile Asn Pro Gln Gly Lys Ala Phe

130 135 140

Arg Ser Lys Val Glu Leu Ile Ala Tyr Phe Glu Lys Val Gly Asp Thr

145 150 155 160

Ser Leu Asp Pro Asn Asp Phe Asp Phe Thr Val Thr Gly Arg Gly Ser

165 170 175

Pro Ser Arg Arg Glu Gln Lys Pro Pro Lys Lys Pro Lys Ser Pro Lys

180 185 190

Ala Pro Gly Thr Gly Arg Gly Arg Gly Arg Pro Lys Gly Ser Gly Thr

195 200 205

Thr Arg Pro Lys Ala Ala Thr Ser Glu Gly Val Gln Val Lys Arg Val

210 215 220

Leu Glu Lys Ser Pro Gly Lys Leu Leu Val Lys Met Pro Phe Gln Thr

225 230 235 240

Ser Pro Gly Gly Lys Ala Glu Gly Gly Gly Ala Thr Thr Ser Thr Gln

245 250 255

Val Met Val Ile Lys Arg Pro Gly Arg Lys Arg Lys Ala Glu Ala Asp

260 265 270

Pro Gln Ala Ile Pro Lys Lys Arg Gly Arg Lys Pro Gly Ser Val Val

275 280 285

Ala Ala Ala Ala Ala Glu Ala Lys Lys Lys Ala Val Lys Glu Ser Ser

290 295 300

Ile Arg Ser Val Gln Glu Thr Val Leu Pro Ile Lys Lys Arg Lys Thr

305 310 315 320

Arg Glu Thr Val Ser Ile Glu Val Lys Glu Val Val Lys Pro Leu Leu

325 330 335

Val Ser Thr Leu Gly Glu Lys Ser Gly Lys Gly Leu Lys Thr Cys Lys

340 345 350

Ser Pro Gly Arg Lys Ser Lys Glu Ser Ser Pro Lys Gly Arg Ser Ser

355 360 365

Ser Ala Ser Ser Pro Pro Lys Lys Glu His His His His His His His

370 375 380

Ser Glu Ser Pro Lys Ala Pro Val Pro Leu Leu Pro Pro Leu Pro Pro

385 390 395 400

Pro Pro Pro Glu Pro Glu Ser Ser Glu Asp Pro Thr Ser Pro Pro Glu

405 410 415

Pro Gln Asp Leu Ser Ser Ser Val Cys Lys Glu Glu Lys Met Pro Arg

420 425 430

Gly Gly Ser Leu Glu Ser Asp Gly Cys Pro Lys Glu Pro Ala Lys Thr

435 440 445

Gln Pro Ala Val Ala Thr Ala Ala Thr Ala Ala Glu Lys Tyr Lys His

450 455 460

Arg Gly Glu Gly Glu Arg Lys Asp Ile Val Ser Ser Ser Met Pro Arg

465 470 475 480

Pro Asn Arg Glu Glu Pro Val Asp Ser Arg Thr Pro Val Thr Glu Arg

485 490 495

Val Ser

<210> 146

<211> 743

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(743)

<223> N-乙酰基-α-氨基葡糖苷酶 (NAGLU)

<400> 146

Met Glu Ala Val Ala Val Ala Ala Ala Val Gly Val Leu Leu Leu Ala

1 5 10 15

Gly Ala Gly Gly Ala Ala Gly Asp Glu Ala Arg Glu Ala Ala Ala Val

20 25 30

Arg Ala Leu Val Ala Arg Leu Leu Gly Pro Gly Pro Ala Ala Asp Phe

35 40 45

Ser Val Ser Val Glu Arg Ala Leu Ala Ala Lys Pro Gly Leu Asp Thr

50 55 60

Tyr Ser Leu Gly Gly Gly Gly Ala Ala Arg Val Arg Val Arg Gly Ser

65 70 75 80

Thr Gly Val Ala Ala Ala Ala Gly Leu His Arg Tyr Leu Arg Asp Phe

85 90 95

Cys Gly Cys His Val Ala Trp Ser Gly Ser Gln Leu Arg Leu Pro Arg

100 105 110

Pro Leu Pro Ala Val Pro Gly Glu Leu Thr Glu Ala Thr Pro Asn Arg

115 120 125

Tyr Arg Tyr Tyr Gln Asn Val Cys Thr Gln Ser Tyr Ser Phe Val Trp

130 135 140

Trp Asp Trp Ala Arg Trp Glu Arg Glu Ile Asp Trp Met Ala Leu Asn

145 150 155 160

Gly Ile Asn Leu Ala Leu Ala Trp Ser Gly Gln Glu Ala Ile Trp Gln

165 170 175

Arg Val Tyr Leu Ala Leu Gly Leu Thr Gln Ala Glu Ile Asn Glu Phe

180 185 190

Phe Thr Gly Pro Ala Phe Leu Ala Trp Gly Arg Met Gly Asn Leu His

195 200 205

Thr Trp Asp Gly Pro Leu Pro Pro Ser Trp His Ile Lys Gln Leu Tyr

210 215 220

Leu Gln His Arg Val Leu Asp Gln Met Arg Ser Phe Gly Met Thr Pro

225 230 235 240

Val Leu Pro Ala Phe Ala Gly His Val Pro Glu Ala Val Thr Arg Val

245 250 255

Phe Pro Gln Val Asn Val Thr Lys Met Gly Ser Trp Gly His Phe Asn

260 265 270

Cys Ser Tyr Ser Cys Ser Phe Leu Leu Ala Pro Glu Asp Pro Ile Phe

275 280 285

Pro Ile Ile Gly Ser Leu Phe Leu Arg Glu Leu Ile Lys Glu Phe Gly

290 295 300

Thr Asp His Ile Tyr Gly Ala Asp Thr Phe Asn Glu Met Gln Pro Pro

305 310 315 320

Ser Ser Glu Pro Ser Tyr Leu Ala Ala Ala Thr Thr Ala Val Tyr Glu

325 330 335

Ala Met Thr Ala Val Asp Thr Glu Ala Val Trp Leu Leu Gln Gly Trp

340 345 350

Leu Phe Gln His Gln Pro Gln Phe Trp Gly Pro Ala Gln Ile Arg Ala

355 360 365

Val Leu Gly Ala Val Pro Arg Gly Arg Leu Leu Val Leu Asp Leu Phe

370 375 380

Ala Glu Ser Gln Pro Val Tyr Thr Arg Thr Ala Ser Phe Gln Gly Gln

385 390 395 400

Pro Phe Ile Trp Cys Met Leu His Asn Phe Gly Gly Asn His Gly Leu

405 410 415

Phe Gly Ala Leu Glu Ala Val Asn Gly Gly Pro Glu Ala Ala Arg Leu

420 425 430

Phe Pro Asn Ser Thr Met Val Gly Thr Gly Met Ala Pro Glu Gly Ile

435 440 445

Ser Gln Asn Glu Val Val Tyr Ser Leu Met Ala Glu Leu Gly Trp Arg

450 455 460

Lys Asp Pro Val Pro Asp Leu Ala Ala Trp Val Thr Ser Phe Ala Ala

465 470 475 480

Arg Arg Tyr Gly Val Ser His Pro Asp Ala Gly Ala Ala Trp Arg Leu

485 490 495

Leu Leu Arg Ser Val Tyr Asn Cys Ser Gly Glu Ala Cys Arg Gly His

500 505 510

Asn Arg Ser Pro Leu Val Arg Arg Pro Ser Leu Gln Met Asn Thr Ser

515 520 525

Ile Trp Tyr Asn Arg Ser Asp Val Phe Glu Ala Trp Arg Leu Leu Leu

530 535 540

Thr Ser Ala Pro Ser Leu Ala Thr Ser Pro Ala Phe Arg Tyr Asp Leu

545 550 555 560

Leu Asp Leu Thr Arg Gln Ala Val Gln Glu Leu Val Ser Leu Tyr Tyr

565 570 575

Glu Glu Ala Arg Ser Ala Tyr Leu Ser Lys Glu Leu Ala Ser Leu Leu

580 585 590

Arg Ala Gly Gly Val Leu Ala Tyr Glu Leu Leu Pro Ala Leu Asp Glu

595 600 605

Val Leu Ala Ser Asp Ser Arg Phe Leu Leu Gly Ser Trp Leu Glu Gln

610 615 620

Ala Arg Ala Ala Ala Val Ser Glu Ala Glu Ala Asp Phe Tyr Glu Gln

625 630 635 640

Asn Ser Arg Tyr Gln Leu Thr Leu Trp Gly Pro Glu Gly Asn Ile Leu

645 650 655

Asp Tyr Ala Asn Lys Gln Leu Ala Gly Leu Val Ala Asn Tyr Tyr Thr

660 665 670

Pro Arg Trp Arg Leu Phe Leu Glu Ala Leu Val Asp Ser Val Ala Gln

675 680 685

Gly Ile Pro Phe Gln Gln His Gln Phe Asp Lys Asn Val Phe Gln Leu

690 695 700

Glu Gln Ala Phe Val Leu Ser Lys Gln Arg Tyr Pro Ser Gln Pro Arg

705 710 715 720

Gly Asp Thr Val Asp Leu Ala Lys Lys Ile Phe Leu Lys Tyr Tyr Pro

725 730 735

Gly Trp Val Ala Gly Ser Trp

740

<210> 147

<400> 147

000

<210> 148

<211> 429

<212> PRT

<213> 智人

<220>

<221> MISC_FEATURE

<222> (1)..(429)

<223> α-半乳糖苷酶 A (GLA)

<400> 148

Met Gln Leu Arg Asn Pro Glu Leu His Leu Gly Cys Ala Leu Ala Leu

1 5 10 15

Arg Phe Leu Ala Leu Val Ser Trp Asp Ile Pro Gly Ala Arg Ala Leu

20 25 30

Asp Asn Gly Leu Ala Arg Thr Pro Thr Met Gly Trp Leu His Trp Glu

35 40 45

Arg Phe Met Cys Asn Leu Asp Cys Gln Glu Glu Pro Asp Ser Cys Ile

50 55 60

Ser Glu Lys Leu Phe Met Glu Met Ala Glu Leu Met Val Ser Glu Gly

65 70 75 80

Trp Lys Asp Ala Gly Tyr Glu Tyr Leu Cys Ile Asp Asp Cys Trp Met

85 90 95

Ala Pro Gln Arg Asp Ser Glu Gly Arg Leu Gln Ala Asp Pro Gln Arg

100 105 110

Phe Pro His Gly Ile Arg Gln Leu Ala Asn Tyr Val His Ser Lys Gly

115 120 125

Leu Lys Leu Gly Ile Tyr Ala Asp Val Gly Asn Lys Thr Cys Ala Gly

130 135 140

Phe Pro Gly Ser Phe Gly Tyr Tyr Asp Ile Asp Ala Gln Thr Phe Ala

145 150 155 160

Asp Trp Gly Val Asp Leu Leu Lys Phe Asp Gly Cys Tyr Cys Asp Ser

165 170 175

Leu Glu Asn Leu Ala Asp Gly Tyr Lys His Met Ser Leu Ala Leu Asn

180 185 190

Arg Thr Gly Arg Ser Ile Val Tyr Ser Cys Glu Trp Pro Leu Tyr Met

195 200 205

Trp Pro Phe Gln Lys Pro Asn Tyr Thr Glu Ile Arg Gln Tyr Cys Asn

210 215 220

His Trp Arg Asn Phe Ala Asp Ile Asp Asp Ser Trp Lys Ser Ile Lys

225 230 235 240

Ser Ile Leu Asp Trp Thr Ser Phe Asn Gln Glu Arg Ile Val Asp Val

245 250 255

Ala Gly Pro Gly Gly Trp Asn Asp Pro Asp Met Leu Val Ile Gly Asn

260 265 270

Phe Gly Leu Ser Trp Asn Gln Gln Val Thr Gln Met Ala Leu Trp Ala

275 280 285

Ile Met Ala Ala Pro Leu Phe Met Ser Asn Asp Leu Arg His Ile Ser

290 295 300

Pro Gln Ala Lys Ala Leu Leu Gln Asp Lys Asp Val Ile Ala Ile Asn

305 310 315 320

Gln Asp Pro Leu Gly Lys Gln Gly Tyr Gln Leu Arg Gln Gly Asp Asn

325 330 335

Phe Glu Val Trp Glu Arg Pro Leu Ser Gly Leu Ala Trp Ala Val Ala

340 345 350

Met Ile Asn Arg Gln Glu Ile Gly Gly Pro Arg Ser Tyr Thr Ile Ala

355 360 365

Val Ala Ser Leu Gly Lys Gly Val Ala Cys Asn Pro Ala Cys Phe Ile

370 375 380

Thr Gln Leu Leu Pro Val Lys Arg Lys Leu Gly Phe Tyr Glu Trp Thr

385 390 395 400

Ser Arg Leu Arg Ser His Ile Asn Pro Thr Gly Thr Val Leu Leu Gln

405 410 415

Leu Glu Asn Thr Met Gln Met Ser Leu Lys Asp Leu Leu

420 425

<210> 149

<211> 458

<212> PRT

<213> 人工序列

<220>

<223> 密码子优化的+ GET, CO1-GLA-GET

<400> 149

Met Gln Leu Arg Asn Pro Glu Leu His Leu Gly Cys Ala Leu Ala Leu

1 5 10 15

Arg Phe Leu Ala Leu Val Ser Trp Asp Ile Pro Gly Ala Arg Ala Leu

20 25 30

Asp Asn Gly Leu Ala Arg Thr Pro Thr Met Gly Trp Leu His Trp Glu

35 40 45

Arg Phe Met Cys Asn Leu Asp Cys Gln Glu Glu Pro Asp Ser Cys Ile

50 55 60

Ser Glu Lys Leu Phe Met Glu Met Ala Glu Leu Met Val Ser Glu Gly

65 70 75 80

Trp Lys Asp Ala Gly Tyr Glu Tyr Leu Cys Ile Asp Asp Cys Trp Met

85 90 95

Ala Pro Gln Arg Asp Ser Glu Gly Arg Leu Gln Ala Asp Pro Gln Arg

100 105 110

Phe Pro His Gly Ile Arg Gln Leu Ala Asn Tyr Val His Ser Lys Gly

115 120 125

Leu Lys Leu Gly Ile Tyr Ala Asp Val Gly Asn Lys Thr Cys Ala Gly

130 135 140

Phe Pro Gly Ser Phe Gly Tyr Tyr Asp Ile Asp Ala Gln Thr Phe Ala

145 150 155 160

Asp Trp Gly Val Asp Leu Leu Lys Phe Asp Gly Cys Tyr Cys Asp Ser

165 170 175

Leu Glu Asn Leu Ala Asp Gly Tyr Lys His Met Ser Leu Ala Leu Asn

180 185 190

Arg Thr Gly Arg Ser Ile Val Tyr Ser Cys Glu Trp Pro Leu Tyr Met

195 200 205

Trp Pro Phe Gln Lys Pro Asn Tyr Thr Glu Ile Arg Gln Tyr Cys Asn

210 215 220

His Trp Arg Asn Phe Ala Asp Ile Asp Asp Ser Trp Lys Ser Ile Lys

225 230 235 240

Ser Ile Leu Asp Trp Thr Ser Phe Asn Gln Glu Arg Ile Val Asp Val

245 250 255

Ala Gly Pro Gly Gly Trp Asn Asp Pro Asp Met Leu Val Ile Gly Asn

260 265 270

Phe Gly Leu Ser Trp Asn Gln Gln Val Thr Gln Met Ala Leu Trp Ala

275 280 285

Ile Met Ala Ala Pro Leu Phe Met Ser Asn Asp Leu Arg His Ile Ser

290 295 300

Pro Gln Ala Lys Ala Leu Leu Gln Asp Lys Asp Val Ile Ala Ile Asn

305 310 315 320

Gln Asp Pro Leu Gly Lys Gln Gly Tyr Gln Leu Arg Gln Gly Asp Asn

325 330 335

Phe Glu Val Trp Glu Arg Pro Leu Ser Gly Leu Ala Trp Ala Val Ala

340 345 350

Met Ile Asn Arg Gln Glu Ile Gly Gly Pro Arg Ser Tyr Thr Ile Ala

355 360 365

Val Ala Ser Leu Gly Lys Gly Val Ala Cys Asn Pro Ala Cys Phe Ile

370 375 380

Thr Gln Leu Leu Pro Val Lys Arg Lys Leu Gly Phe Tyr Glu Trp Thr

385 390 395 400

Ser Arg Leu Arg Ser His Ile Asn Pro Thr Gly Thr Val Leu Leu Gln

405 410 415

Leu Glu Asn Thr Met Gln Met Ser Leu Lys Asp Leu Leu Arg Arg Arg

420 425 430

Arg Arg Arg Arg Arg Lys Arg Lys Lys Lys Gly Lys Gly Leu Gly Lys

435 440 445

Lys Arg Asp Pro Cys Leu Arg Lys Tyr Lys

450 455

<210> 150

<211> 1428

<212> PRT

<213> 人工序列

<220>

<223> 密码子优化的，囊性纤维化跨膜调节蛋白 △R

(CFTR△R)含有R结构域缺失

<400> 150

Met Gln Arg Ser Pro Leu Glu Lys Ala Ser Val Val Ser Lys Leu Phe

1 5 10 15

Phe Ser Trp Thr Arg Pro Ile Leu Arg Lys Gly Tyr Arg Gln Arg Leu

20 25 30

Glu Leu Ser Asp Ile Tyr Gln Ile Pro Ser Val Asp Ser Ala Asp Asn

35 40 45

Leu Ser Glu Lys Leu Glu Arg Glu Trp Asp Arg Glu Leu Ala Ser Lys

50 55 60

Lys Asn Pro Lys Leu Ile Asn Ala Leu Arg Arg Cys Phe Phe Trp Arg

65 70 75 80

Phe Met Phe Tyr Gly Ile Phe Leu Tyr Leu Gly Glu Val Thr Lys Ala

85 90 95

Val Gln Pro Leu Leu Leu Gly Arg Ile Ile Ala Ser Tyr Asp Pro Asp

100 105 110

Asn Lys Glu Glu Arg Ser Ile Ala Ile Tyr Leu Gly Ile Gly Leu Cys

115 120 125

Leu Leu Phe Ile Val Arg Thr Leu Leu Leu His Pro Ala Ile Phe Gly

130 135 140

Leu His His Ile Gly Met Gln Met Arg Ile Ala Met Phe Ser Leu Ile

145 150 155 160

Tyr Lys Lys Thr Leu Lys Leu Ser Ser Arg Val Leu Asp Lys Ile Ser

165 170 175

Ile Gly Gln Leu Val Ser Leu Leu Ser Asn Asn Leu Asn Lys Phe Asp

180 185 190

Glu Gly Leu Ala Leu Ala His Phe Val Trp Ile Ala Pro Leu Gln Val

195 200 205

Ala Leu Leu Met Gly Leu Ile Trp Glu Leu Leu Gln Ala Ser Ala Phe

210 215 220

Cys Gly Leu Gly Phe Leu Ile Val Leu Ala Leu Phe Gln Ala Gly Leu

225 230 235 240

Gly Arg Met Met Met Lys Tyr Arg Asp Gln Arg Ala Gly Lys Ile Ser

245 250 255

Glu Arg Leu Val Ile Thr Ser Glu Met Ile Glu Asn Ile Gln Ser Val

260 265 270

Lys Ala Tyr Cys Trp Glu Glu Ala Met Glu Lys Met Ile Glu Asn Leu

275 280 285

Arg Gln Thr Glu Leu Lys Leu Thr Arg Lys Ala Ala Tyr Val Arg Tyr

290 295 300

Phe Asn Ser Ser Ala Phe Phe Phe Ser Gly Phe Phe Val Val Phe Leu

305 310 315 320

Ser Val Leu Pro Tyr Ala Leu Ile Lys Gly Ile Ile Leu Arg Lys Ile

325 330 335

Phe Thr Thr Ile Ser Phe Cys Ile Val Leu Arg Met Ala Val Thr Arg

340 345 350

Gln Phe Pro Trp Ala Val Gln Thr Trp Tyr Asp Ser Leu Gly Ala Ile

355 360 365

Asn Lys Ile Gln Asp Phe Leu Gln Lys Gln Glu Tyr Lys Thr Leu Glu

370 375 380

Tyr Asn Leu Thr Thr Thr Glu Val Val Met Glu Asn Val Thr Ala Phe

385 390 395 400

Trp Glu Glu Gly Phe Gly Glu Leu Phe Glu Lys Ala Lys Gln Asn Asn

405 410 415

Asn Asn Arg Lys Thr Ser Asn Gly Asp Asp Ser Leu Phe Phe Ser Asn

420 425 430

Phe Ser Leu Leu Gly Thr Pro Val Leu Lys Asp Ile Asn Phe Lys Ile

435 440 445

Glu Arg Gly Gln Leu Leu Ala Val Ala Gly Ser Thr Gly Ala Gly Lys

450 455 460

Thr Ser Leu Leu Met Met Ile Met Gly Glu Leu Glu Pro Ser Glu Gly

465 470 475 480

Lys Ile Lys His Ser Gly Arg Ile Ser Phe Cys Ser Gln Phe Ser Trp

485 490 495

Ile Met Pro Gly Thr Ile Lys Glu Asn Ile Ile Phe Gly Val Ser Tyr

500 505 510

Asp Glu Tyr Arg Tyr Arg Ser Val Ile Lys Ala Cys Gln Leu Glu Glu

515 520 525

Asp Ile Ser Lys Phe Ala Glu Lys Asp Asn Ile Val Leu Gly Glu Gly

530 535 540

Gly Ile Thr Leu Ser Gly Gly Gln Arg Ala Arg Ile Ser Leu Ala Arg

545 550 555 560

Ala Val Tyr Lys Asp Ala Asp Leu Tyr Leu Leu Asp Ser Pro Phe Gly

565 570 575

Tyr Leu Asp Val Leu Thr Glu Lys Glu Ile Phe Glu Ser Cys Val Cys

580 585 590

Lys Leu Met Ala Asn Lys Thr Arg Ile Leu Val Thr Ser Lys Met Glu

595 600 605

His Leu Lys Lys Ala Asp Lys Ile Leu Ile Leu His Glu Gly Ser Ser

610 615 620

Tyr Phe Tyr Gly Thr Phe Ser Glu Leu Gln Asn Leu Gln Pro Asp Phe

625 630 635 640

Ser Ser Lys Leu Met Gly Cys Asp Ser Phe Asp Gln Phe Ser Ala Glu

645 650 655

Arg Arg Asn Ser Ile Leu Thr Glu Thr Leu His Arg Phe Ser Leu Glu

660 665 670

Gly Asp Ala Pro Val Ser Trp Thr Glu Thr Lys Lys Gln Ser Phe Lys

675 680 685

Gln Thr Gly Glu Phe Gly Glu Lys Arg Lys Asn Ser Ile Leu Asn Pro

690 695 700

Ile Asn Ser Thr Leu Gln Ala Arg Arg Arg Gln Ser Val Leu Asn Leu

705 710 715 720

Met Thr His Ser Val Asn Gln Gly Gln Asn Ile His Arg Lys Thr Thr

725 730 735

Ala Ser Thr Arg Lys Val Ser Leu Ala Pro Gln Ala Asn Leu Thr Glu

740 745 750

Leu Asp Ile Tyr Ser Arg Arg Leu Ser Gln Glu Thr Gly Leu Glu Ile

755 760 765

Ser Glu Glu Ile Asn Glu Glu Asp Leu Lys Glu Cys Phe Phe Asp Asp

770 775 780

Met Glu Ser Ile Pro Ala Val Thr Thr Trp Asn Thr Tyr Leu Arg Tyr

785 790 795 800

Ile Thr Val His Lys Ser Leu Ile Phe Val Leu Ile Trp Cys Leu Val

805 810 815

Ile Phe Leu Ala Glu Val Ala Ala Ser Leu Val Val Leu Trp Leu Leu

820 825 830

Gly Asn Thr Pro Leu Gln Asp Lys Gly Asn Ser Thr His Ser Arg Asn

835 840 845

Asn Ser Tyr Ala Val Ile Ile Thr Ser Thr Ser Ser Tyr Tyr Val Phe

850 855 860

Tyr Ile Tyr Val Gly Val Ala Asp Thr Leu Leu Ala Met Gly Phe Phe

865 870 875 880

Arg Gly Leu Pro Leu Val His Thr Leu Ile Thr Val Ser Lys Ile Leu

885 890 895

His His Lys Met Leu His Ser Val Leu Gln Ala Pro Met Ser Thr Leu

900 905 910

Asn Thr Leu Lys Ala Gly Gly Ile Leu Asn Arg Phe Ser Lys Asp Ile

915 920 925

Ala Ile Leu Asp Asp Leu Leu Pro Leu Thr Ile Phe Asp Phe Ile Gln

930 935 940

Leu Leu Leu Ile Val Ile Gly Ala Ile Ala Val Val Ala Val Leu Gln

945 950 955 960

Pro Tyr Ile Phe Val Ala Thr Val Pro Val Ile Val Ala Phe Ile Met

965 970 975

Leu Arg Ala Tyr Phe Leu Gln Thr Ser Gln Gln Leu Lys Gln Leu Glu

980 985 990

Ser Glu Gly Arg Ser Pro Ile Phe Thr His Leu Val Thr Ser Leu Lys

995 1000 1005

Gly Leu Trp Thr Leu Arg Ala Phe Gly Arg Gln Pro Tyr Phe Glu

1010 1015 1020

Thr Leu Phe His Lys Ala Leu Asn Leu His Thr Ala Asn Trp Phe

1025 1030 1035

Leu Tyr Leu Ser Thr Leu Arg Trp Phe Gln Met Arg Ile Glu Met

1040 1045 1050

Ile Phe Val Ile Phe Phe Ile Ala Val Thr Phe Ile Ser Ile Leu

1055 1060 1065

Thr Thr Gly Glu Gly Glu Gly Arg Val Gly Ile Ile Leu Thr Leu

1070 1075 1080

Ala Met Asn Ile Met Ser Thr Leu Gln Trp Ala Val Asn Ser Ser

1085 1090 1095

Ile Asp Val Asp Ser Leu Met Arg Ser Val Ser Arg Val Phe Lys

1100 1105 1110

Phe Ile Asp Met Pro Thr Glu Gly Lys Pro Thr Lys Ser Thr Lys

1115 1120 1125

Pro Tyr Lys Asn Gly Gln Leu Ser Lys Val Met Ile Ile Glu Asn

1130 1135 1140

Ser His Val Lys Lys Asp Asp Ile Trp Pro Ser Gly Gly Gln Met

1145 1150 1155

Thr Val Lys Asp Leu Thr Ala Lys Tyr Thr Glu Gly Gly Asn Ala

1160 1165 1170

Ile Leu Glu Asn Ile Ser Phe Ser Ile Ser Pro Gly Gln Arg Val

1175 1180 1185

Gly Leu Leu Gly Arg Thr Gly Ser Gly Lys Ser Thr Leu Leu Ser

1190 1195 1200

Ala Phe Leu Arg Leu Leu Asn Thr Glu Gly Glu Ile Gln Ile Asp

1205 1210 1215

Gly Val Ser Trp Asp Ser Ile Thr Leu Gln Gln Trp Arg Lys Ala

1220 1225 1230

Phe Gly Val Ile Pro Gln Lys Val Phe Ile Phe Ser Gly Thr Phe

1235 1240 1245

Arg Lys Asn Leu Asp Pro Tyr Glu Gln Trp Ser Asp Gln Glu Ile

1250 1255 1260

Trp Lys Val Ala Asp Glu Val Gly Leu Arg Ser Val Ile Glu Gln

1265 1270 1275

Phe Pro Gly Lys Leu Asp Phe Val Leu Val Asp Gly Gly Cys Val

1280 1285 1290

Leu Ser His Gly His Lys Gln Leu Met Cys Leu Ala Arg Ser Val

1295 1300 1305

Leu Ser Lys Ala Lys Ile Leu Leu Leu Asp Glu Pro Ser Ala His

1310 1315 1320

Leu Asp Pro Val Thr Tyr Gln Ile Ile Arg Arg Thr Leu Lys Gln

1325 1330 1335

Ala Phe Ala Asp Cys Thr Val Ile Leu Cys Glu His Arg Ile Glu

1340 1345 1350

Ala Met Leu Glu Cys Gln Gln Phe Leu Val Ile Glu Glu Asn Lys

1355 1360 1365

Val Arg Gln Tyr Asp Ser Ile Gln Lys Leu Leu Asn Glu Arg Ser

1370 1375 1380

Leu Phe Arg Gln Ala Ile Ser Pro Ser Asp Arg Val Lys Leu Phe

1385 1390 1395

Pro His Arg Asn Ser Ser Lys Cys Lys Ser Lys Pro Gln Ile Ala

1400 1405 1410

Ala Leu Lys Glu Glu Thr Glu Glu Glu Val Gln Asp Thr Arg Leu

1415 1420 1425

<210> 151

<211> 1480

<212> PRT

<213> 人工序列

<220>

<223> 密码子优化的，全长囊性纤维化跨膜

调节蛋白 (CFTR)

<400> 151

Met Gln Arg Ser Pro Leu Glu Lys Ala Ser Val Val Ser Lys Leu Phe

1 5 10 15

Phe Ser Trp Thr Arg Pro Ile Leu Arg Lys Gly Tyr Arg Gln Arg Leu

20 25 30

Glu Leu Ser Asp Ile Tyr Gln Ile Pro Ser Val Asp Ser Ala Asp Asn

35 40 45

Leu Ser Glu Lys Leu Glu Arg Glu Trp Asp Arg Glu Leu Ala Ser Lys

50 55 60

Lys Asn Pro Lys Leu Ile Asn Ala Leu Arg Arg Cys Phe Phe Trp Arg

65 70 75 80

Phe Met Phe Tyr Gly Ile Phe Leu Tyr Leu Gly Glu Val Thr Lys Ala

85 90 95

Val Gln Pro Leu Leu Leu Gly Arg Ile Ile Ala Ser Tyr Asp Pro Asp

100 105 110

Asn Lys Glu Glu Arg Ser Ile Ala Ile Tyr Leu Gly Ile Gly Leu Cys

115 120 125

Leu Leu Phe Ile Val Arg Thr Leu Leu Leu His Pro Ala Ile Phe Gly

130 135 140

Leu His His Ile Gly Met Gln Met Arg Ile Ala Met Phe Ser Leu Ile

145 150 155 160

Tyr Lys Lys Thr Leu Lys Leu Ser Ser Arg Val Leu Asp Lys Ile Ser

165 170 175

Ile Gly Gln Leu Val Ser Leu Leu Ser Asn Asn Leu Asn Lys Phe Asp

180 185 190

Glu Gly Leu Ala Leu Ala His Phe Val Trp Ile Ala Pro Leu Gln Val

195 200 205

Ala Leu Leu Met Gly Leu Ile Trp Glu Leu Leu Gln Ala Ser Ala Phe

210 215 220

Cys Gly Leu Gly Phe Leu Ile Val Leu Ala Leu Phe Gln Ala Gly Leu

225 230 235 240

Gly Arg Met Met Met Lys Tyr Arg Asp Gln Arg Ala Gly Lys Ile Ser

245 250 255

Glu Arg Leu Val Ile Thr Ser Glu Met Ile Glu Asn Ile Gln Ser Val

260 265 270

Lys Ala Tyr Cys Trp Glu Glu Ala Met Glu Lys Met Ile Glu Asn Leu

275 280 285

Arg Gln Thr Glu Leu Lys Leu Thr Arg Lys Ala Ala Tyr Val Arg Tyr

290 295 300

Phe Asn Ser Ser Ala Phe Phe Phe Ser Gly Phe Phe Val Val Phe Leu

305 310 315 320

Ser Val Leu Pro Tyr Ala Leu Ile Lys Gly Ile Ile Leu Arg Lys Ile

325 330 335

Phe Thr Thr Ile Ser Phe Cys Ile Val Leu Arg Met Ala Val Thr Arg

340 345 350

Gln Phe Pro Trp Ala Val Gln Thr Trp Tyr Asp Ser Leu Gly Ala Ile

355 360 365

Asn Lys Ile Gln Asp Phe Leu Gln Lys Gln Glu Tyr Lys Thr Leu Glu

370 375 380

Tyr Asn Leu Thr Thr Thr Glu Val Val Met Glu Asn Val Thr Ala Phe

385 390 395 400

Trp Glu Glu Gly Phe Gly Glu Leu Phe Glu Lys Ala Lys Gln Asn Asn

405 410 415

Asn Asn Arg Lys Thr Ser Asn Gly Asp Asp Ser Leu Phe Phe Ser Asn

420 425 430

Phe Ser Leu Leu Gly Thr Pro Val Leu Lys Asp Ile Asn Phe Lys Ile

435 440 445

Glu Arg Gly Gln Leu Leu Ala Val Ala Gly Ser Thr Gly Ala Gly Lys

450 455 460

Thr Ser Leu Leu Met Met Ile Met Gly Glu Leu Glu Pro Ser Glu Gly

465 470 475 480

Lys Ile Lys His Ser Gly Arg Ile Ser Phe Cys Ser Gln Phe Ser Trp

485 490 495

Ile Met Pro Gly Thr Ile Lys Glu Asn Ile Ile Phe Gly Val Ser Tyr

500 505 510

Asp Glu Tyr Arg Tyr Arg Ser Val Ile Lys Ala Cys Gln Leu Glu Glu

515 520 525

Asp Ile Ser Lys Phe Ala Glu Lys Asp Asn Ile Val Leu Gly Glu Gly

530 535 540

Gly Ile Thr Leu Ser Gly Gly Gln Arg Ala Arg Ile Ser Leu Ala Arg

545 550 555 560

Ala Val Tyr Lys Asp Ala Asp Leu Tyr Leu Leu Asp Ser Pro Phe Gly

565 570 575

Tyr Leu Asp Val Leu Thr Glu Lys Glu Ile Phe Glu Ser Cys Val Cys

580 585 590

Lys Leu Met Ala Asn Lys Thr Arg Ile Leu Val Thr Ser Lys Met Glu

595 600 605

His Leu Lys Lys Ala Asp Lys Ile Leu Ile Leu His Glu Gly Ser Ser

610 615 620

Tyr Phe Tyr Gly Thr Phe Ser Glu Leu Gln Asn Leu Gln Pro Asp Phe

625 630 635 640

Ser Ser Lys Leu Met Gly Cys Asp Ser Phe Asp Gln Phe Ser Ala Glu

645 650 655

Arg Arg Asn Ser Ile Leu Thr Glu Thr Leu His Arg Phe Ser Leu Glu

660 665 670

Gly Asp Ala Pro Val Ser Trp Thr Glu Thr Lys Lys Gln Ser Phe Lys

675 680 685

Gln Thr Gly Glu Phe Gly Glu Lys Arg Lys Asn Ser Ile Leu Asn Pro

690 695 700

Ile Asn Ser Ile Arg Lys Phe Ser Ile Val Gln Lys Thr Pro Leu Gln

705 710 715 720

Met Asn Gly Ile Glu Glu Asp Ser Asp Glu Pro Leu Glu Arg Arg Leu

725 730 735

Ser Leu Val Pro Asp Ser Glu Gln Gly Glu Ala Ile Leu Pro Arg Ile

740 745 750

Ser Val Ile Ser Thr Gly Pro Thr Leu Gln Ala Arg Arg Arg Gln Ser

755 760 765

Val Leu Asn Leu Met Thr His Ser Val Asn Gln Gly Gln Asn Ile His

770 775 780

Arg Lys Thr Thr Ala Ser Thr Arg Lys Val Ser Leu Ala Pro Gln Ala

785 790 795 800

Asn Leu Thr Glu Leu Asp Ile Tyr Ser Arg Arg Leu Ser Gln Glu Thr

805 810 815

Gly Leu Glu Ile Ser Glu Glu Ile Asn Glu Glu Asp Leu Lys Glu Cys

820 825 830

Phe Phe Asp Asp Met Glu Ser Ile Pro Ala Val Thr Thr Trp Asn Thr

835 840 845

Tyr Leu Arg Tyr Ile Thr Val His Lys Ser Leu Ile Phe Val Leu Ile

850 855 860

Trp Cys Leu Val Ile Phe Leu Ala Glu Val Ala Ala Ser Leu Val Val

865 870 875 880

Leu Trp Leu Leu Gly Asn Thr Pro Leu Gln Asp Lys Gly Asn Ser Thr

885 890 895

His Ser Arg Asn Asn Ser Tyr Ala Val Ile Ile Thr Ser Thr Ser Ser

900 905 910

Tyr Tyr Val Phe Tyr Ile Tyr Val Gly Val Ala Asp Thr Leu Leu Ala

915 920 925

Met Gly Phe Phe Arg Gly Leu Pro Leu Val His Thr Leu Ile Thr Val

930 935 940

Ser Lys Ile Leu His His Lys Met Leu His Ser Val Leu Gln Ala Pro

945 950 955 960

Met Ser Thr Leu Asn Thr Leu Lys Ala Gly Gly Ile Leu Asn Arg Phe

965 970 975

Ser Lys Asp Ile Ala Ile Leu Asp Asp Leu Leu Pro Leu Thr Ile Phe

980 985 990

Asp Phe Ile Gln Leu Leu Leu Ile Val Ile Gly Ala Ile Ala Val Val

995 1000 1005

Ala Val Leu Gln Pro Tyr Ile Phe Val Ala Thr Val Pro Val Ile

1010 1015 1020

Val Ala Phe Ile Met Leu Arg Ala Tyr Phe Leu Gln Thr Ser Gln

1025 1030 1035

Gln Leu Lys Gln Leu Glu Ser Glu Gly Arg Ser Pro Ile Phe Thr

1040 1045 1050

His Leu Val Thr Ser Leu Lys Gly Leu Trp Thr Leu Arg Ala Phe

1055 1060 1065

Gly Arg Gln Pro Tyr Phe Glu Thr Leu Phe His Lys Ala Leu Asn

1070 1075 1080

Leu His Thr Ala Asn Trp Phe Leu Tyr Leu Ser Thr Leu Arg Trp

1085 1090 1095

Phe Gln Met Arg Ile Glu Met Ile Phe Val Ile Phe Phe Ile Ala

1100 1105 1110

Val Thr Phe Ile Ser Ile Leu Thr Thr Gly Glu Gly Glu Gly Arg

1115 1120 1125

Val Gly Ile Ile Leu Thr Leu Ala Met Asn Ile Met Ser Thr Leu

1130 1135 1140

Gln Trp Ala Val Asn Ser Ser Ile Asp Val Asp Ser Leu Met Arg

1145 1150 1155

Ser Val Ser Arg Val Phe Lys Phe Ile Asp Met Pro Thr Glu Gly

1160 1165 1170

Lys Pro Thr Lys Ser Thr Lys Pro Tyr Lys Asn Gly Gln Leu Ser

1175 1180 1185

Lys Val Met Ile Ile Glu Asn Ser His Val Lys Lys Asp Asp Ile

1190 1195 1200

Trp Pro Ser Gly Gly Gln Met Thr Val Lys Asp Leu Thr Ala Lys

1205 1210 1215

Tyr Thr Glu Gly Gly Asn Ala Ile Leu Glu Asn Ile Ser Phe Ser

1220 1225 1230

Ile Ser Pro Gly Gln Arg Val Gly Leu Leu Gly Arg Thr Gly Ser

1235 1240 1245

Gly Lys Ser Thr Leu Leu Ser Ala Phe Leu Arg Leu Leu Asn Thr

1250 1255 1260

Glu Gly Glu Ile Gln Ile Asp Gly Val Ser Trp Asp Ser Ile Thr

1265 1270 1275

Leu Gln Gln Trp Arg Lys Ala Phe Gly Val Ile Pro Gln Lys Val

1280 1285 1290

Phe Ile Phe Ser Gly Thr Phe Arg Lys Asn Leu Asp Pro Tyr Glu

1295 1300 1305

Gln Trp Ser Asp Gln Glu Ile Trp Lys Val Ala Asp Glu Val Gly

1310 1315 1320

Leu Arg Ser Val Ile Glu Gln Phe Pro Gly Lys Leu Asp Phe Val

1325 1330 1335

Leu Val Asp Gly Gly Cys Val Leu Ser His Gly His Lys Gln Leu

1340 1345 1350

Met Cys Leu Ala Arg Ser Val Leu Ser Lys Ala Lys Ile Leu Leu

1355 1360 1365

Leu Asp Glu Pro Ser Ala His Leu Asp Pro Val Thr Tyr Gln Ile

1370 1375 1380

Ile Arg Arg Thr Leu Lys Gln Ala Phe Ala Asp Cys Thr Val Ile

1385 1390 1395

Leu Cys Glu His Arg Ile Glu Ala Met Leu Glu Cys Gln Gln Phe

1400 1405 1410

Leu Val Ile Glu Glu Asn Lys Val Arg Gln Tyr Asp Ser Ile Gln

1415 1420 1425

Lys Leu Leu Asn Glu Arg Ser Leu Phe Arg Gln Ala Ile Ser Pro

1430 1435 1440

Ser Asp Arg Val Lys Leu Phe Pro His Arg Asn Ser Ser Lys Cys

1445 1450 1455

Lys Ser Lys Pro Gln Ile Ala Ala Leu Lys Glu Glu Thr Glu Glu

1460 1465 1470

Glu Val Gln Asp Thr Arg Leu

1475 1480

<210> 152

<211> 250

<212> DNA

<213> 人工序列

<220>

<223> 小鼠U1a启动子

<400> 152

atggaggcgg tactatgtag atgagaattc aggagcaaac tgggaaaagc aactgcttcc 60

aaatatttgt gatttttaca gtgtagtttt ggaaaaactc ttagcctacc aattcttcta 120

agtgttttaa aatgtgggag ccagtacaca tgaagttata gagtgtttta atgaggctta 180

aatatttacc gtaactatga aatgctacgc atatcatgct gttcaggctc cgtggccacg 240

caactcatac 250

<210> 153

<211> 101

<212> DNA

<213> 人工序列

<220>

<223> 聚合酶III H1突变启动子

<400> 153

aatatttgca tgtcgctatg tgttctggga aatcaccata aacgtgaaat gtctttggat 60

ttgggaatct tcgaagttct gtatgagacc acagatctcc a 101

<210> 154

<211> 701

<212> DNA

<213> 人工序列

<220>

<223> 鸡β-肌动蛋白杂合启动子 CBh (CBh启动子由

CMV增强子、CBA启动子、第一CBA外显子和部分内含子组成)

<400> 154

cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt 60

gacgtcaata gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg 120

gtaaactgcc cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga 180

cgtcaatgac ggtaaatggc ccgcctggca ttgtgcccag tacatgacct tatgggactt 240

tcctacttgg cagtacatct acgtattagt catcgctatt accatggtcg aggtgagccc 300

cacgttctgc ttcactctcc ccatctcccc cccctcccca cccccaattt tgtatttatt 360

tattttttaa ttattttgtg cagcgatggg ggcggggggg gggggggggc gcgcgccagg 420

cggggcgggg cggggcgagg ggcggggcgg ggcgaggcgg agaggtgcgg cggcagccaa 480

tcagagcggc gcgctccgaa agtttccttt tatggcgagg cggcggcggc ggcggcccta 540

taaaaagcga agcgcgcggc gggcgggagt cgctgcgcgc tgccttcgcc ccgtgccccg 600

ctccgccgcc gcctcgcgcc gcccgccccg gctctgactg accgcgttac tcccacaggt 660

gagcgggcgg gacggccctt ctcctccggg ctgtaattag c 701

<210> 155

<211> 229

<212> DNA

<213> 人工序列

<220>

<223> MeCP2 min启动子序列

<400> 155

agctgaatgg ggtccgcctc ttttccctgc ctaaacagac aggaactcct gccaattgag 60

ggcgtcaccg ctaaggctcc gccccagcct gggctccaca accaatgaag ggtaatctcg 120

acaaagagca aggggtgggg cgcgggcgcg caggtgcagc agcacacagg ctggtcggga 180

gggcggggcg cgacgtctgc cgtgcggggt cccggcatcg gttgcgcgc 229

<210> 156

<211> 737

<212> DNA

<213> 人工序列

<220>

<223> MeCP2启动子序列

<400> 156

tcaaaccatc tgattcaaca atgcacgacc gatctcttat gggcttggca cacaccatct 60

gcccattata aacgtctgca aagaccaagg tttgatatgt tgattttact gtcagcctta 120

agagtgcgac atctgctaat ttagtgtaat aatacaatca gtagaccctt taaaacaagt 180

cccttggctt ggaacaacgc caggctcctc aacaggcaac tttgctactt ctacagaaaa 240

tgataataaa gaaatgctgg tgaagtcaaa tgcttatcac aatggtgaac tactcagcag 300

ggaggctcta ataggcgcca agagcctaga cttccttaag cgccagagtc cacaagggcc 360

cagttaatcc tcaacattca aatgctgccc acaaaaccag cccctctgtg ccctagccgc 420

ctcttttttc caagtgacag tagaactcca ccaatccgca gctgaatggg gtccgcctct 480

tttccctgcc taaacagaca ggaactcctg ccaattgagg gcgtcaccgc taaggctccg 540

ccccagcctg ggctccacaa ccaatgaagg gtaatctcga caaagagcaa ggggtggggc 600

gcgggcgcgc aggtgcagca gcacacaggc tggtcgggag ggcggggcgc gacgtctgcc 660

gtgcggggtc ccggcatcgg ttgcgcgcgc gctccctcct ctcggagaga gggctgtggt 720

aaaacccgtc cggaaaa 737

<210> 157

<211> 418

<212> DNA

<213> 人工序列

<220>

<223> MeCP418启动子序列

<400> 157

ataggcgcca agagcctaga cttccttaag cgccagagtc cacaagggcc cagttaatcc 60

tcaacattca aatgctgccc acaaaaccag cccctctgtg ccctagccgc ctcttttttc 120

caagtgacag tagaactcca ccaatccgca gctgaatggg gtccgcctct tttccctgcc 180

taaacagaca ggaactcctg ccaattgagg gcgtcaccgc taaggctccg ccccagcctg 240

ggctccacaa ccaatgaagg gtaatctcga caaagagcaa ggggtggggc gcgggcgcgc 300

aggtgcagca gcacacaggc tggtcgggag ggcggggcgc gacgtctgcc gtgcggggtc 360

ccggcatcgg ttgcgcgcgc gctccctcct ctcggagaga gggctgtggt aaaacccg 418

<210> 158

<211> 426

<212> DNA

<213> 人工序列

<220>

<223> MeCP426启动子序列

<400> 158

ataggcgcca agagcctaga cttccttaag cgccagagtc cacaagggcc cagttaatcc 60

tcaacattca aatgctgccc acaaaaccag cccctctgtg ccctagccgc ctcttttttc 120

caagtgacag tagaactcca ccaatccgca gctgaatggg gtccgcctct tttccctgcc 180

taaacagaca ggaactcctg ccaattgagg gcgtcaccgc taaggctccg ccccagcctg 240

ggctccacaa ccaatgaagg gtaatctcga caaagagcaa ggggtggggc gcgggcgcgc 300

aggtgcagca gcacacaggc tggtcgggag ggcggggcgc gacgtctgcc gtgcggggtc 360

ccggcatcgg ttgcgcgcgc gctccctcct ctcggagaga gggctgtggt aaaacccgtc 420

cggaaa 426

<210> 159

<211> 400

<212> DNA

<213> 人工序列

<220>

<223> VMD2启动子

<400> 159

aattctgtca ttttactagg gtgatgaaat tcccaagcaa caccatcctt ttcagataag 60

ggcactgagg ctgagagagg agctgaaacc tacccggggt caccacacac aggtggcaag 120

gctgggacca gaaaccagga ctgttgactc tggattttag ggccatggta gagggggtgt 180

tgccctaaat tccagccctg gtctcagccc aacaccctcc aagaagaaat tagaggggcc 240

atggccaggc tgtgctagcc gttgcttctg agcagattac aagaagggac taagacaagg 300

actcctttgt ggaggtcctg gcttagggag tcaagtgacg gcggctcagc actcacgtgg 360

gcagtgccag cctctaagag tgggcagggg cactggccac 400

<210> 160

<211> 136

<212> DNA

<213> 人工序列

<220>

<223> PDE6b启动子

<400> 160

cccatttgta ggagtgagtc agctgacccg cccccggggt tcctaatctc actaagaaag 60

actttgctga tgacagggtt tcctgggagt ccatgcgtgc ctggagcagc agcgtctcca 120

gggacaggca gccacc 136

<210> 161

<211> 2035

<212> DNA

<213> 人工序列

<220>

<223> mRho启动子

<400> 161

gcgccaatca gccgatgact tctaacaata ctcttaactc acacagagct tgtctcactg 60

agccaacacc ctgtaccctc agctcagtga cggctttcaa cctgtggggc tgcctctgtt 120

acccaagtga gagagggcca gtgctcccag aggtgacctt gtttgcccat tctctccctg 180

ggtcagccag tgtttatctg ttgtataccc agtccaccct gcaggctcac atcagagcct 240

aggagatggc tagtgtcccc gcggagacca cgatgaagct tcccagctgt ctcaagcaca 300

agctggctgc agaggctgct gaggcactgc tagctgggga tgggggcagg gtagatctgg 360

ggctgaccac cagggtcaga atcagaacct ccaccttgac ctcattaacg ctggtcttaa 420

tcaccaagcc aagctcctta aactgctagt ggccaactcc caggccctga cacacatacc 480

tgccctgtgt tcccaaacaa gacacctgca tggaaggaag ggggttgctt ttctaagcaa 540

acatctagga atcccgggtg cagtgtgagg agactaggcg agggagtact ttaagggcct 600

caaggctcag agaggaatac ttcttccctg gttagcctcg tgcctaggct ccagggtctt 660

tgtcctgcct ggatacctat gtggcaaggg gcatagcatt tcccccacca tcagctctta 720

gctcaacctt atcttctcgg aaagactgcg cagtgtaaca acacagcaga gacttttctt 780

ttgtcccctg tctacccctg taactgctac tcagaagcat ctttctcaca gggtactggc 840

ttcttgcatc cagagttttt tgtctccctc gggcccccag aatcaaattc ttcctctggg 900

actcagtgga tgtttcacac acgtatcggc ctgacagtca tcctggagca tcctacacag 960

gggccatcac agctgcatgt cagaaatgct ggcctcacat cctcagacac caggcctagt 1020

gctggtcttc ctcagactgg cgtccccagc aggccagtag gatcatcttt tagcctacag 1080

agttctgaag cctcagagcc ccaggtccct ggtcatcttc tctgcccctg agatttttcc 1140

aagttgtatg ccttctaggt aaggcaaaac ttcttacgcc cctcctcgtg gcctccaggc 1200

cccacatgct cacctgaata acctggcagc ctgctccctc atgcagggac cacgtcctgc 1260

tgcacccagc aggccatccc gtctccatag cccatggtca tccctccctg gacaggaatg 1320

tgtctcctcc ccgggctgag tcttgctcaa gctagaagca ctccgaacag ggttatgggc 1380

gcctcctcca tctcccaagt ggctggctta tgaatgttta atgtacatgt gagtgaacaa 1440

attccaattg aacgcaacaa atagttatcg agccgctgag ccggggggcg gggggtgtga 1500

gactggaggc gatggacgga gctgacggca cacacagctc agatctgtca agtgagccat 1560

tgtcagggct tggggactgg ataagtcagg gggtctcctg ggaagagatg ggataggtga 1620

gttcaggagg agacattgtc aactggagcc atgtggagaa gtgaatttag ggcccaaagg 1680

ttccagtcgc agcctgaggc caccagactg acatggggag gaattcccag aggactctgg 1740

ggcagacaag atgagacacc ctttcctttc tttacctaag ggcctccacc cgatgtcacc 1800

ttggcccctc tgcaagccaa ttaggccccg gtggcagcag tgggattagc gttagtatga 1860

tatctcgcgg atgctgaatc agcctctggc ttagggagag aaggtcactt tataagggtc 1920

tggggggggt cagtgcctgg agttgcgctg tgggagccgt cagtggctga gctcgccaag 1980

cagccttggt ctctgtctac gaagagcccg tggggcagcc tcgagagccg cagcc 2035

<210> 162

<211> 511

<212> DNA

<213> 人工序列

<220>

<223> CMV启动子

<400> 162

ccgttacata acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat 60

tgacgtcaat agtaacgcca atagggactt tccattgacg tcaatgggtg gagtatttac 120

ggtaaactgc ccacttggca gtacatcaag tgtatcatat gccaagtacg ccccctattg 180

acgtcaatga cggtaaatgg cccgcctggc attgtgccca gtacatgacc ttatgggact 240

ttcctacttg gcagtacatc tacgtattag tcatcgctat taccatggtg atgcggtttt 300

ggcagtacat caatgggcgt ggatagcggt ttgactcacg gggatttcca agtctccacc 360

ccattgacgt caatgggagt ttgttttggc accaaaatca acgggacttt ccaaaatgtc 420

gtaacaactc cgccccattg acgcaaatgg gcggtaggcg tgtacggtgg gaggtctata 480

taagcagagc tcgtttagtg aaccgtcaga t 511

<210> 163

<211> 334

<212> DNA

<213> 人工序列

<220>

<223> UbC启动子

<400> 163

ggcctccgcg ccgggttttg gcgcctcccg cgggcgcccc cctcctcacg gcgagcgctg 60

ccacgtcaga cgaagggcgc agcgagcgtc ctgatccttc cgcccggacg ctcaggacag 120

cggcccgctg ctcataagac tcggccttag aaccccagta tcagcagaag gacattttag 180

gacgggactt gggtgactct agggcactgg ttttctttcc agagagcgga acaggcgagg 240

aaaagtagtc ccttctcggc gattctgcgg agggatctcc gtggggcggt gaacgccgat 300

gattatataa ggacgcgccg ggtgtggcac agct 334

Claims

1.一种编码AAV衣壳蛋白的核酸，所述AAV衣壳蛋白包含VP1部分、VP2部分和VP3部分，其中所述VP3部分包含可变区(VR)I至IX，其中：

(a)VR-II包含氨基酸序列DNNGVK(SEQ ID NO:54)，

(b)VR-III包含氨基酸序列NDGS(SEQ ID NO:55)，

(c)VR-IV包含氨基酸序列INGSGQNQQT(SEQ ID NO:56)，

(d)VR-V包含氨基酸序列RVSTTTGQNNSNFAWTA(SEQ ID NO:57)，

(e)VR-VI包含氨基酸序列HKEGEDRFFPLSG(SEQ ID NO:58)，

(f)VR-VII包含氨基酸序列KQNAARDNADYSDV(SEQ ID NO:59)，

(g)VR-VIII包含氨基酸序列ADNLQQQNTAPQI(SEQ ID NO:60)，以及

(h)VR-IX包含氨基酸序列NYYKSTSVDF(SEQ ID NO:61)。

2.根据权利要求1所述的核酸，其中所述VR-I区包含NSTSGGSS(SEQ ID NO:53)或SSTSGGSS(SEQ ID NO:87)。

3.根据权利要求1或2所述的核酸，其中所述VR-I区包含SASTGAS(SEQ ID NO:52)。

4.根据权利要求1至3中任一项所述的核酸，其中所述VP3部分具有SEQ ID NO:41的序列。

5.根据权利要求2所述的核酸，其中所述编码的AAV衣壳氨基酸序列与SEQ NO 30或SEQID NO84的氨基酸序列具有至少95％的同一性。

6.根据权利要求3所述的核酸，其中所述编码的AAV衣壳氨基酸序列与SEQ ID NO:3、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33或SEQ ID NO:34的氨基酸序列具有至少95％的同一性。

7.根据权利要求4所述的核酸，其中所述核酸序列与选自SEQ ID NO:18-23的核苷酸序列具有至少95％的同一性。

8.根据权利要求7所述的核酸，其中所述核酸序列与选自SEQ ID NO:18-23的核苷酸序列具有100％的同一性。

9.一种载体，包含根据权利要求1至8所述的核酸。

10.一种AAV衣壳蛋白，由根据权利要求1至8所述的核酸编码。

11.根据权利要求10所述的AAV衣壳蛋白，其中所述蛋白包含SEQ ID NO:3、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33或SEQ ID NO:34的氨基酸序列。

12.一种AAV病毒载体，包含由根据权利要求1至8所述的核酸编码的AAV衣壳蛋白和AAV载体，其中所述AAV载体沿5’至3’方向包含

(a)第一AAV反向末端重复，

(b)启动子，

(c)异源核酸，

(d)poly-A尾；以及

(e)第二AAV反向末端重复。

13.根据权利要求12所述的AAV病毒载体，其中所述异源核酸与组成型启动子可操作地连接。

14.根据权利要求12所述的AAV病毒载体，其中所述异源核酸编码多肽。

15.根据权利要求12所述的AAV病毒载体，其中异源核酸编码反义RNA、微RNA或RNAi。

16.根据权利要求12所述的AAV病毒载体，其中所述AAV衣壳蛋白包含SEQ ID NO:3、SEQID NO:31、SEQ ID NO:32、SEQ ID NO:33或SEQ ID NO:34的氨基酸序列。

17.一种AAV病毒载体，包含

(i)AAV衣壳蛋白，所述AAV衣壳蛋白具有SEQ ID NO2、SEQ ID NO:3、SEQ ID NO:31、SEQID NO:32、SEQ ID NO:33或SEQ ID NO:34的氨基酸序列，以及

(ii)AAV载体，其中所述AAV载体沿5’至3’方向包含

(a)第一AAV反向末端重复，

(b)启动子，

(c)异源核酸，

(d)poly-A尾；以及

(e)第二AAV反向末端重复。

18.根据权利要求12或17所述的AAV病毒载体，其中所述异源核酸

编码mRNA、siRNA、gRNA或微RNA。

19.根据权利要求12或17所述的AAV病毒载体，其中所述异源核酸编码多肽。

20.根据权利要求19所述的AAV病毒载体，其中所述异源基因序列编码囊性纤维化跨膜传导调节蛋白(CFTR)、CLN3蛋白、α-半乳糖苷酶A(GLA)或酸性α-葡糖苷酶(GAA)。

21.根据权利要求20所述的AAV病毒载体，其中所述异源序列编码CFTR。

22.根据权利要求21所述的AAV病毒载体，其中所述CFTR包含由SEQ ID NO:4编码的氨基酸序列。

23.根据权利要求19所述的AAV病毒载体，其中所述异源基因序列编码包含与SEQ IDNO:5、8、11和14中的任一个具有至少70％、80％、90％或99％同一性的氨基酸序列的蛋白质。

24.根据权利要求19所述的AAV病毒载体，其中所述异源基因序列包含与SEQ ID NO:4、5、6、7、9、10、12和13中的任一个具有至少70％、80％、90％或99％同一性的序列。

25.根据权利要求12或17所述的AAV病毒载体，其中所述启动子是劳斯肉瘤病毒(RSV)LTR启动子(任选地与RSV增强子一起)、巨细胞病毒(CMV)启动子、SV40启动子、二氢叶酸还原酶启动子、β-肌动蛋白启动子、磷酸甘油激酶(PGK)启动子、U6启动子、H1启动子、CAG启动子、杂合鸡β-肌动蛋白启动子、MeCP2启动子、EF1启动子、遍在鸡β-肌动蛋白杂合(CBh)启动子、U1a启动子、U1b启动子、MeCP2启动子、MeP418启动子、MeP426启动子、最小MeCP2启动子、VMD2启动子、mRho启动子、EFla启动子、Ubc启动子、人β-肌动蛋白启动子、TRE启动子、Ac5启动子、多角体蛋白启动子、CaMKIIa启动子、Gal1启动子、TEF1启动子、GDS启动子、ADH1启动子、Ubi启动子或α-1-抗胰蛋白酶(hAAT)启动子。

26.一种治疗疾病或病症的方法，包括向受试者施用根据根据权利要求12-25中任一项所述的AAV病毒载体。

27.根据权利要求26的方法，其中所述AAV病毒载体经口、直肠、透粘膜、吸入、经皮、肠胃外、静脉内、皮下、皮内、肌内、胸膜内、脑内、鞘内、脑内、心室内、鼻内、耳内、眼内或眼周、局部、淋巴内、脑池内或玻璃体内施用给所述受试者。

28.根据根据权利要求26所述的方法，其中所述疾病或病症是肌萎缩性侧索硬化(ALS)、脊髓性肌萎缩(SMA)、法布里病、庞皮病、CLN3病(或青少年神经元蜡样质脂褐质沉积症)、隐性营养不良性大疱性表皮松解症(RDEB)、青少年巴特氏病、常染色体显性病症、肌营养不良、血友病A、血友病B、多发性硬化、糖尿病、戈谢病、癌症、关节炎、肌肉消瘦、心脏病、内膜增生、癫痫、亨延顿氏舞蹈病、帕金森病、阿尔茨海默病、囊性纤维化、地中海贫血、赫尔勒综合征、Sly综合征、沙伊综合征、胡-射二氏综合征、亨特综合征、Sanfilippo综合征A(粘多糖贮积病IIIA或MPS IIIA)、Sanfilippo综合征B(粘多糖贮积病IIIB或MPS IIIB)、Sanfilippo综合征C、Sanfilippo综合征D、莫基奥综合征、马-兰二氏综合征、克腊比氏病、苯丙酮尿症、巴特氏病、脊髓小脑性共济失调、LDL受体缺乏、高血氨症、关节炎、黄斑变性、色素性视网膜炎、神经元蜡样质脂褐质沉积症1(CLN1)或腺苷脱氨酶缺乏。