CN106906241B - 增强腺相关病毒载体功能的方法 - Google Patents

增强腺相关病毒载体功能的方法 Download PDF

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CN106906241B
CN106906241B CN201611102646.6A CN201611102646A CN106906241B CN 106906241 B CN106906241 B CN 106906241B CN 201611102646 A CN201611102646 A CN 201611102646A CN 106906241 B CN106906241 B CN 106906241B
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L·范登伯格
G·高
J·M·威尔森
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Abstract

本发明提供了一种在选定的腺相关病毒(AAV)序列中校正单现突变从而提高选定AAV的包装产量、转导效率和/或基因转移效率的方法。该方法包括改变亲代AAV衣壳中的一个或多个单现突变，使它们与用来比对的功能性AAV衣壳序列中相应位点上的氨基酸相一致。

Description

增强腺相关病毒载体功能的方法
本申请是国际申请PCT/US2006/013375，国际申请日2006年4月7日，中国 国家阶段申请号200680010566.6，名称“增强腺相关病毒载体功能的方法”的发明 专利申请的分案申请。
发明背景
腺相关病毒(AAV)是细小病毒科(Parvovirus)家族的一个成员，它是小的无包膜、二十面体病毒，具有4.7千碱基(kb)到6kb的单链线性DNA基因组。由于该 病毒是作为纯化的腺病毒原种的污染物被发现的，AAV指定为依赖病毒属 (Dependovirus)。AAV的生命周期包括潜伏期(AAV基因组在感染后位点特异性整合 入宿主染色体)，感染期(腺病毒或单纯疱疹病毒感染后，整合的基因组接着得到 拯救、复制并包装入感染的病毒)。非致病性、宽宿主范围(包括非分裂细胞)感染 性以及潜在的位点特异性染色体整合的特性使得AAV成为用于基因转移的有吸引 力的工具。
已经描述AAV载体用于治疗用和免疫原性分子的运载工具。迄今为止，已从 人或非人灵长类(NHP)中分离了几种表征良好的不同AAV。
最近，研究者描述了不同序列的大量AAV[G.Gao等人，Proc Natl Acad Sci USA，100(10):6081-6086(2003年5月13日)；US-2003-0138772-A1(2003年7月24日)]， 并且将这些AAV表征为不同的血清型和分化体[G.Gao等人，J.Virol.， 78(12):6381-6388(2004年6月)；国际专利公开号WO 2005/033321]。已报道不同 的AAV表现出不同的转染效率，也表现出对不同细胞或组织的趋性。
想要得到用于向不同细胞类型递送异源分子的基于AAV的构建体。
发明概述
本发明提供了一种用于改善无功能和/或功能弱的AAV载体的方法。
一方面，该方法提供了一种在选定的腺相关病毒(AAV)序列中校正单现突变(singleton)以提高选定AAV的包装产量、转导效率和/或基因转移效率的方法。该 方法包括改变亲代AAV衣壳中的一个或多个单现突变使所述单现突变与用来比对 的功能性AAV衣壳序列中对应位点的氨基酸相一致。
另一方面，本发明提供了经修正的AAV序列，即除去一个或多个单现突变的 序列。
又一方面，本发明提供了具有根据本发明修正的AAV衣壳的AAV载体。
下述发明详述容易地表现出本发明的其他方面和优点。
附图简述
图1显示经单现突变校正的AAV载体的体外293转导。在载体名称之后标明 了单现突变的校正(如果存在的话)，数字表示突变的数目。
图2A-2C显示用293细胞测定的AAV载体在感染复数范围为101到104的滴 度，其中，图2A比较亲代rh.8和经单现突变校正的rh.8(rh.8R)，图2B比较亲代 rh.37和经修正的rh.37，图2C比较AAV2和AAV8。作为对照，还给出了AAV2和 AAV2/8eGFP表达载体的相似滴定的结果。Y轴表示以流式细胞计数法测定的eGFP 阳性细胞百分比(％)。
图3是AAV序列的系统发生树，显示了它们的系统发生关系和所属分化体。
图4A-4L是AAV2[SEQ ID NO:7]、cy.5[SEQ ID NO:8]、rh.10[SEQ ID NO:9]、rh.13[SEQ ID NO:10]、AAV1[SEQ ID NO:11]、AAV3[SEQ ID NO:12]、AAV6[SEQ ID NO:13]、AAV7[SEQ ID NO:14]、AAV8[SEQ ID NO:15]、hu.13[SEQ ID NO:16]、hu.26[SEQ ID NO:17]、hu.37[SEQ ID NO:18]、hu.53[SEQ ID NO:19]、rh.39[SEQ ID NO:20]、 rh.43[SEQ IDNO:21]和rh.46[SEQ ID NO:22]的衣壳蛋白(vp1)核酸序列的比对。
图5A-5D是AAV2[SEQ ID NO:23]、cy.5[SEQ ID NO:24]、rh.10[SEQ ID NO:25]、rh.13[SEQ ID NO:26]、AAV1[SEQ ID NO:27]、AAV3[SEQ ID NO:28]、AAV6[SEQ ID NO:29]、AAV7[SEQ ID NO:30]、AAV8[SEQ ID NO:31]、hu.13[SEQ ID NO:32]、hu.26[SEQ ID NO:33]、hu.37[SEQ ID NO:34]、hu.53[SEQ ID NO:35]、rh.39[SEQ ID NO:36]、 rh.43[SEQ IDNO:37]和rh.46[SEQ ID NO:38]的衣壳蛋白(vp1)氨基酸序列的比对。
图6A-6B是rh.13[SEQ ID NO:26]、rh.2[SEQ ID NO:39]、rh.8[SEQ ID NO:41]、hu.29[SEQ ID NO:42]和rh.64[SEQ ID NO:43]的衣壳蛋白(vp1)氨基酸序列的比对。
发明详述
本发明提供了一种改善AAV载体功能的方法。本发明尤其适合于改善衣壳含 一个或多个单现突变的AAV载体的包装产量、转导效率和/或基因转移效率。本 发明进一步提供了根据本发明的方法鉴定和制备的新AAV衣壳序列。
本说明书与权利要求书使用的术语“包含/含有”和“包括”包括其他成分、元 素、数值、步骤等等在内。相反，术语“由...组成”和其变体不包括其他成分、元 素、数值、步骤等等在内。
本发明的单现突变方法
如本文中所用的术语“单现突变(singleton)”指在选定的(即亲代)AAV衣壳序列中的给定位点上的可变氨基酸。通过将亲代AAV衣壳序列与功能性AAV衣壳序列 文库比对来确定可变氨基酸的存在。然后分析序列来确定亲代AAV衣壳中所有这 样的可变氨基酸序列：功能性AAV文库中的AAV序列在此氨基酸位置完全保守。 然后改变亲代AAV序列，将单现突变改变为经鉴定功能性AAV衣壳序列在该位点 上的保守氨基酸。根据本发明，亲代AAV序列可能具有1-6、1-5、1-4、1-3或2 个单现突变。亲代AAV序列也可能具有超过6个单现突变。
一旦修正后，经修正的AAV衣壳可用于构建具有经修正衣壳的AAV载体。可 使用本领域技术人员公知的技术来构建载体。
根据本发明方法所选择的用于修正的AAV是想要与亲代AAV相比增强其下列 三种功能特性之一或多种的AAV，所述的三种功能特性即：包装成具有选定AAV 序列的衣壳的病毒粒子，提高转导效率或增加基因转移效率。例如，与密切相关 的其他AAV相比，亲代AAV的特征可能在于具有较低的包装效率。在另一个实例 中，与密切相关的AAV相比，亲代AAV可能具有较低的转导效率。在另一个实例 中，与密切相关的AAV相比，亲代AAV可能具有较低的基因转移效率(即：体内 递送靶分子的能力较低)。在其他的实例中，亲代AAV的上述各项功能都合格，但 有待进一步提高其中一项或多项功能。
因此，本发明提供了一种功能性AAV的文库，其中AVV的序列与选定的(亲 代)AAV形成对照。适宜的是，该文库包含具有目标功能的AAV，该目标功能正是 欲在选定亲代AAV实现的改善。换句话说，该功能性AAV文库的每一序列的特征 在于具有目标水平的包装能力、目标水平的体外转导效率或目标水平的体内基因 转移效率(即：在对象中向选定靶组织或细胞的递送能力)。组成文库的功能性AAV 可分别具有这些功能性特征中的一种、两种或全部。本领域技术人员可容易地确 定文库的其他目标功能。
在一个实施方案中，功能性AAV是能产生具有与AAV1、AAV2、AAV7、AAV8 或AAV9同等或更强包装和转导效率的病毒粒子的AAV。可用含AAV2rep和AAV2 ITR的假型包装设定(pseudotype setting)来测评功能。因此，可使用常规技术构建 改变的亲代AAV，并且，当与AAV2的产量相比，如果由所属亲代AAV产生病毒 的滴度为至少50％时，则认为该AAV载体是功能性的。另外，本领域技术人员可 容易地确定AAV转导细胞的能力。例如，可构建亲代AAV使其包含易于测知病毒 的标记基因。例如，让AAV包含eGFP或另一可进行荧光检测的基因。如果AAV 包含CMV-eGFP，当将由改变的亲代AAV衣壳产生的病毒以感染复数104转导293细胞时，转导效率大于全部细胞GFP荧光的5％时表示有功能，其中，所述细胞 以感染复数20用野生型人5型腺病毒预处理2小时。
适宜的是，文库由至少三种或至少四种功能性AAV衣壳序列组成，所述序列 代表至少两种不同的分化体。优选地，文库包含各代表性分化体的至少两个序列 。在某些实施方案中提供了三个、四个、五个、六个或更多的分化体。
“分化体”指基于AAV vp1氨基酸序列比对，经邻接算法、自展值(Bootstrapvalue)为至少75％(至少1000次复制)确定，并且泊松校正距离不大于0.05的在系 统发生上彼此相关的一组AAV。
文献中有关于邻接算法(Neighbor-jioning algorithm)的详细描述。参见，例如：M.Nei与S.Kumar，《分子进化与系统发生学》(Molecular Evolution and Pylogenetics)(牛津大学出版社，纽约(2000))。已有现成用于执行该算法的计算机 程序。例如，MEGAv2.1程序执行改进的Nci-Goiobori方法。使用这些技术与计算 机程序，以及AAV vp1衣壳蛋白序列，本领域的技术人员可容易地确定所选定的 AAV是否包含在本文所鉴定的一个分化体内、另一个分化体内、或在这些分化体 之外。
虽然分化体主要基于天然存在的AAV vp1衣壳，但并不限于天然存在的AAV 。分化体可包括非天然存在的AAV，包括但不限于重组、修饰或改变、嵌合、杂 交、合成、人工即其他AVV，只要这些AVV是基于AAV vp1氨基酸序列比对、用 邻接算法(自展值至少75％(至少1000次复制))确定且泊松校正距离测量值不大于 0.05的系统发生上彼此相关的AAV。
所描述的AAV分化体包括分化体A(以AAV1和AAV6为代表)、分化体B(以AAV2 为代表)、分化体C(以AAV2-AAV3杂交体为代表)、分化体D(以AAV7为代表)、分 化体E(以AAV8为代表)与分化体F(以人AAV9为代表)。这些分化体以各自的成员 －一种已知AAV血清型－为代表。已知的AAV1和AAV6同属于一个分化体(分化 体A)，其中包括回收自3人的4种分离株。已知的AAV3和AAV5血清型彼此显著 不同，但在本文所述的筛选中未检测到，没有包括于这些分化体中。
AAV分化体的进一步讨论可见于G.Gao等人，J.Virol.，78(12):6381-6388(2004年6月)和国际专利公开号WO 2004/028817和WO 2005/033321中。后一文件还提 供了新的人AAV序列，此处引用作为参考。
在一个实施方案中，用于本发明方法的文库不包括AAV5。在另一个实施方案 中，用于本发明方法的文库不包括AAV4。然而，在某些实施方案中，例如：当亲 代AAV类似于AAV5时，在比对中可能需要包括该序列。
虽然可构建包含最小数目序列的文库，但是可通过利用包含较多序列的文库 来优化鉴定单现突变的效率。适宜的是，所述文库包含最少四个序列，代表至少 两个分化体。优选地，该文库中，各分化体各自有至少两种代表序列。在一个实 施方案中，该文库包含超过100个AAV序列。在另一个实施方案中，该文库包含 至少3到100个AAV序列。在又一个实施方案中，该文库包含至少6到50个AAV 序列。
适用于本发明功能性文库的AAV包含，例如：AAV1、AAV2、AAV6、AAV7、 AAV8、AAV9及其他已描述的序列，[G.Gao等人，Proc Natl.Acad Sci.， 100(10):6081-6086(2003年5月13日)；国际专利公开号WO 2004/042397和WO 2005/033321)]。本领域技术人员可以容易地选择其他AAV，例如：使用国际专利 公开号WO 03/093460A1(2003年11月13日)和美国专利申请公开号 2003-0138772A1(2003年7月24日)描述的方法所分离的AAV。
根据本发明，所述文库内的所述至少三个序列在衣壳序列全长比对中至少有85％同一性。
蛋白质全长或其片段的氨基酸序列的“同一性百分比(％)”可容易地确定。适宜的是，片段长度至少为大约8个氨基酸，也可长达大约700个氨基酸。通常，当 提及两种不同的腺相关病毒之间的“同一性”、“同源性”或“相似性”时，“同一性”、 “同源性”或“相似性”是参照进行“比对”的序列确定的。“比对”序列或“比对”指这样 的多核酸序列或蛋白质(氨基酸)序列，它们与参考序列相比通常包含碱基或氨基 酸缺失或增加的校正。
可使用各种公知或市售的多序列比对程序进行比对。用于氨基酸序列比对的 程序有例如：“Clustal X”、“MAP”、“PIMA”、“MSA”、“BLOCKMAKER”、“MEME”和 “Match-Box”程序。虽然本领域技术人员可视需要改变设置，但通常这些程序都以 默认设置使用。或者，本领域技术人员也可采用能够象上述算法和程序一样得出 同一性述评或进行比对的其他算法和计算机程序。参见，例如：J.D.Thomson等人， Nucl.Acids.Res.，“多序列比对的综合比较(A comprehensive comparison of multiple sequence alignments)”，27(13):2682-2690(1999)。
也有用于核酸序列的多序列比对程序。这种程序的实例包括通过因特网的网 络服务器可得的“W串(Clustal W)”、“CAP序列组件”、“MAP”和“MEME”。这些程序 的其他来源是本领域技术人员所已知的。或者，也可使用Vector NTI实用程序。 还有许多本领域已知的算法也可用于测量核苷酸序列同一性，包括包含在上述程 序中的算法。作为另一个实例，可使用GCG 6.1版中的程序FastaTM来比较多核苷 酸序列。FastaTM可得出查询序列与检索序列之间最佳重叠区域的对比和序列同一 性百分比。例如，可使用GCG 6.1版提供的默认参数(字长为6和用于计分矩阵的 NOPAM系数)用FastaTM来确定核酸序列之间的序列同一性百分比，该程序此处引 用作为参考。
根据本发明，将被疑包含单现突变的靶或亲代AAV衣壳序列与文库的AAV衣 壳序列进行比较。使用AAV衣壳的全长vp1蛋白序列比对进行该比较。
当AAV序列对齐时，对于选定的氨基酸位点，如果文库中所有AAV在此具有 相同的氨基酸残基(即：是完全保守的)而亲代AAV具有与此不同的氨基酸残基， 则鉴定到单现突变。
一般地，当以AAV衣壳vp1蛋白为基础来进行比对时，该比对包含了如此测 得的与参比AAV序列(例如AAV2)相比的插入和缺失，氨基酸残基的编号是基于该 比对产生的基准标度(reference scale)。但是，任何给定的AAV序列都可能比基准 标度少如干氨基酸残基。在本发明中，当描述亲代AAV和参考文库的序列时，术 语“相同的位点”或“相应的位点”指相对于比对所用的基准标度，各序列氨基酸内 相同编号残基处的氨基酸。但是，在比对之外，各AAV vp1蛋白质内的这些氨基 酸可能在不同编号的残基处。
可选地，可用核酸比对进行本发明方法，并将编码不同氨基酸的密码子(即非 同义密码子)鉴定为单现突变。当亲代AAV中给定密码子的核酸序列虽然与文库中 该密码子的序列不同，但编码的氨基酸相同时，这些不同的密码子序列是同义密 码子而非单现突变。
根据本发明，包含单现突变的亲代AAV被改变为其中的单现突变残基被替换 为文库中AAV的保守氨基酸残基。
可使用常规的定点诱变技术对可变氨基酸的密码子进行上述置换。一般地， 使用仅包括必须步骤的定点诱变来获得想要的保守氨基酸残基的密码子。这样的 方法是本领域技术人员已知的，并可使用公开的方法和/或市售的试剂盒来实行 (例如：可以从Stratagene和Promega获得)。可在AAV基因组序列上实行定点诱变。 为了方便起见可用载体(例如：质粒骨架)携带AAV序列。或者，本领域技术人员可 使用本领域公知的其他技术来改变亲代AAV。
亲代AAV可具有多于一个的单现突变，例如：两个、三个、四个、五个、六 个或更多。但是，可能在一个单现突变校正之后就观察到功能上的改善。在亲代 AAV携带多个单现突变的实施方案中，可以每次改变一个单现突变，随后测定修 正AAV是否最强了想要的功能。或者，可在改变多个单现突变后测定想要的功能 是否增强。
当亲代AAV包含多个单现突变时，即使第一个单现突变改变后就观察到了功 能的改善，仍可以通过改变其余的单现突变来优化功能。
一般地，根据本发明的方法改变了一个或多个单现突变的亲代AAV通过将AAV 包装成AAV颗粒来测定其功能。本领域技术人员熟知这些方法，参见，例如：如 上引用的G.Gao等人，Proc Natl Acad Sci.；Sambrook等人，分子克隆：实验室手册 (Molecular Cloning:A Laboratory Manual)，冷泉港出版社(冷泉港，纽约)。
这些改变的AAV具有根据本发明方法产生的新的衣壳，并就其功能接受测定 。本文描述了测定AAV功能的适当方法，包括，例如：产生脱氧核糖核酸酶(DNAse) 保护颗粒能力、体外细胞转导效率和/或体内基因转移。适宜的是，与亲代AAV 的功能相比，本发明改变的AAV具有足够数目的单现突变被改变从而增强了这些 特征性功能中一项或全部。
II.本发明的新AAV
本发明进一步提供了预测新AAV是否有功能的方法。该方法包含使用本发明 的单现突变方法和鉴定选定AAV序列中单现突变的缺失，即没有单现突变的AAV 。
因此，在一个实施方案中，本发明提供了选择AAV用于产生载体的方法。该 方法包括选择待分析的亲代AAV衣壳序列，并在亲代AAV衣壳序列和功能性AAV衣 壳序列文库的比对中鉴定亲代AAV衣壳上单现突变的缺失。一旦确定选定AAV衣壳 没有单现突变，则该AVV可根据已知技术用来产生载体。
当术语“基本同源性”或“基本相似性”用于核酸或其片段时意味着当与另一核 酸(或其互补链)进行包含适当的核苷酸插入或缺失的最佳比对时，比对序列的至 少约95％到99％具有核苷酸序同一性。优选在全长序列、或其开放读码框、或其 他至少长15个核苷酸的合适片段上具有上述同源性。本文描述了合适片段的实例 。
文中用于核酸序列时，术语“序列同一性”、“序列同一性百分比”或“同一性百 分比”指在最佳匹配比对中，两条序列的残基相同。序列同一性比较的长度可以是 基因组全长、基因编码序列的全长，或需要至少约500到5000个核苷酸的片段。然 而，也可能要求较小片段之间的同一性，例如至少约9个核苷酸、通常至少约20 到24个核苷酸、至少约28到32个核苷酸、至少约36或更多核苷酸的片段。
当术语“基本同源性”或“基本相似性”用于描述氨基酸或其片段时意味着当与 另一氨基酸(或其互补链)进行包含适当的氨基酸插入或缺失的最佳比对时，对比 序列的至少约95％到99％具有氨基酸序列同一性，在某些实施方案中，对比序列 中的约97％具有同一性。优选在全长序列，或其蛋白(例如，cap蛋白、rep蛋白) 或其至少8个氨基酸、或更理想至少15个氨基酸长度的片段上具有上述同源性。本 文描述了合适片段的实例。
术语“高度保守的”表示至少80％的同一性，优选至少90％的同一性，更优选超 过97％的同一性。本领域技术人员可根据本领域已知的算法和程序容易地确定同 一性。
术语“血清型”是指具有衣壳的AAV在血清学上不同于其他AAV血清型区别。血 清学区别是基于该AAV的抗体与其他AVV没有交叉反应来确定的。交叉反应性通常 用中和抗体试验测定。为了进行该试验，使用腺相关病毒在兔子或其他合适动物 模型中产生抗特定AAV的多克隆血清。在该试验中，随后测试所产生的特定AAV 的抗血清中和相同(同源)或异源AAV的能力。将达到50％中和作用的稀释度作为中 和抗体滴度。如果就两种AAV而言，异源滴度除以同源滴度之商的倒数小于16， 则此两种载体被认为是相同的血清型。相反，如果异源滴度与同源滴度之比的倒 数是16或更大，则这两种AAV被认为是不同的血清型。
在另外的的实施方案中，本发明提供了具有新的衣壳的AAV，包括rh.20、 rh.32/33、rh.39、rh.46、rh.73和rh.74。rh.20的序列具有SEQ ID NO:1的氨基酸序列 或与全长SEQ ID NO:1具有95-99％同一性的序列。rh.32/33的衣壳具有SEQ ID NO:2 的氨基酸序列或与全长SEQ ID NO:2具有95-99％同一性的序列。rh.39的衣壳具有 SEQ ID NO:3的氨基酸序列或与全长SEQ ID NO:3具有95-99％同一性的序列。rh.46的 衣壳具有SEQ ID NO:4的氨基酸序列或与全长SEQ ID NO:4具有95-99％同一性的序 列。rh.73的衣壳具有SEQ IDNO:5的氨基酸序列或与全长SEQ ID NO:5具有95-99％同 一性的序列。rh.74的衣壳具有SEQ ID NO:6的氨基酸序列或与全长SEQ ID NO:6具有 95-99％同一性的序列。优选地，这些新AAV衣壳序列的同一性达到使它们没有任 何单现突变的程度。新AAV序列见序列表。
在又一个实施方案中，本发明的新AAV序列包括经单现突变校正的AAV衣壳蛋 白和编码这些衣壳蛋白的序列。适当的经单现突变校正的AAV序列的实例包括 AAV6.1、AAV6.2、AAV6.1.2、rh.8R、rh.48.1、rh.48.2、rh.48.1.2、hu.44R1、hu.44R2、 hu.44R3、hu.29R、ch.5R1、rh.67、rh.54、hu.48R1、hu.48R2和hu.48R3。例如，经 单现突变校正的AAV6包括AAV6.1、AAV6.2和AAV6.12，它们显示了与亲代AAV6序 列相比明显的功能改善。
特别理想的蛋白质包括由如前所述鉴定的核苷酸序列所编码的AAV衣壳蛋白 。所述AAV衣壳由vp1、vp2和vp3这三种蛋白质组成，它们互为剪接变体。衣壳蛋 白的其他理想的片段包括位于高变区(HVR)之间的恒定区和可变区。衣壳蛋白的其 他理想的片段包括HVR本身。
一种开发用于确定AAV2中序列歧变区域的算法得出了12个高变区(HVR)，其 中的5个与先前所述的四个可变区重叠或是其一部分(Chiorini等人，J.Virol.， 73:1309-19(1999)；Rutledge等人，J.Virol.，72:309-319)。使用该算法和/或本文 所描述的比对技术，确定了新AAV血清型的HVR。例如，HVR位于如下位置：HVR1， aa146-152；HVR2，aa182-186；HVR3，aa262-264；HVR4，aa381-383；HVR5，aa450-474 ；HVR6，aa490-495；HVR7，aa500-504；HVR8，aa514-522；HVR9，aa534-555； HVR10，aa581-594；HVR11，aa658-667；以及HVR12，aa705-719[该编号系统是基 于使用AAV2vp1作为参考点的比对]。使用Clustal X程序及其默认设置，或使用其 他市售或公知的比对程序及其默认设置(如本文所述的那些)来进行本文的比对， 本领域技术人员可容易地确定本发明的新AAV衣壳的相应片段。
适宜的是，片段至少长8个氨基酸。但是，也可方便地采用其他所需长度的 片段。可通过重组或其他合适的方法例如化学合成来产生这样的片段。
本发明进一步提供了使用本文所提供的序列信息鉴定的其他AAV序列。例如， 鉴于本文所提供的序列，可使用基因组步移技术(genome walking technology)(Siebert等人，1995，Nucleic Acid Research，23:1087-1088，Friezner-Degen 等人，1986，J.Biol.Chem.261:6972-6985，BD Biosciences Clontech，Palo Alto，CA) 来分离感染性序列。基因组步移技术尤其适合于鉴定和分离与本发明方法所鉴定 的新序列邻近的序列。基于本文所提供的新AAV衣壳序列和rep序列，该技术还可 用于分离新AAV的反向末端重复(ITR)。
可由本发明的AAV核酸序列来表达新的AAV氨基酸序列、肽和蛋白质。另外， 也可通过本领域已知的其他方法来产生这些氨基酸序列、肽和蛋白质，所述方法 包括例如化学合成、其他合成方法或其他方法。可使用多种方法容易地产生本文 提供的任一AAV衣壳序列。
合适的生产技术是本领域技术人员所熟知的。参见，例如：Sambrook等人， 分子克隆：实验室手册(Molecular Cloning:A Laboratory Manual)，冷泉港出版社(冷 泉港，纽约)。或者，还可通过众所周知的固相肽合成法(Merrifield，J.Am.Chem. Soc，85:2149(1962)；Stewart和Young，固相肽合成(Solid Phase Peptide Synthesis)(Freeman，旧金山，1969)，第27-62页)来合成肽。这些及其他适当的生 产方法是本领域技术人员已知的，并且不构成对本发明的限定。
可通过各种合适的方法生产本发明的序列、蛋白质和片段，包括重组生产、 化学合成或其他合成方法。这种生产方法是本领域技术人员已知的，并且不构成 对本发明的限定。
III.具有新AAV衣壳的rAAV的生产
本发明包括在按照本发明方法鉴定单现突变后通过突变产生的新的AAV衣壳 序列。本发明进一步包括新的AAV rh.20、rh.32/33、rh.39、rh.46、rh.73和rh.74衣 壳序列(SEQ ID No:1-6)。
在另一个方面，本发明提供了利用了本发明的新AAV序列(包括其片段)的用于 产生将异源基因或其他核酸序列递送至靶细胞的病毒载体的分子。
本发明含有AAV序列的分子包括有可递送至宿主细胞的各种遗传元件(载体)， 例如：能够传送所带序列的裸DNA、质粒、噬菌体、转座子、粘粒、附加体、非 病毒递送载体中的蛋白质(如：基于脂质的运载体)、病毒等。
选定载体可通过各种合适的方法递送，包括转染、电穿孔、脂质体递送、膜 融合技术、高速DNA包被小球、病毒感染与原生质体融合。用于构建本发明这一 方面实施方式的方法是核酸操作领域(包括遗传工程、重组工程与合成技术)的技 术人员已知的。参见，例如：Sambrook等，分子克隆：实验室手册(Molecular Cloning： A Laboratory Manual)，冷泉港出版社，冷泉港，纽约。
在一个实施方案中，本发明的载体含有编码本发明的AAV衣壳或其片段的序 列及其他元件。在另一个实施方案中，本发明的载体至少含有编码AAV rep蛋白或 其片段的序列。任选地，本发明的载体可含有AAV cap和rep蛋白。在既有AAV rep 又有cap的载体中，AAV rep和AAV cap序列可来源于同一分化体的AAV。或者，本 发明提供含有来自不同AAV的rep序列和cap序列载体。在一个实施方案中，rep和 cap序列由彼此独立的来源(例如：分开的载体，或宿主细胞和载体)表达。在另一 个实施方案中，rep序列与来自不同AAV的cap序列框内融合形成嵌合AAV载体。任 选地，本发明的载体是包装在本发明的AAV衣壳中的载体。这些载体与本文所述 的其他载体可进一步包含含有选定转基因的小基因，转基因两侧是AAV5'ITR和 AAV3'ITR。
因此，在一个实施方案中，本文所述的载体含有编码来自同一AAV序列的完 整AAV衣壳的核酸序列。或者，这些载体含有编码人造衣壳的序列，所述人造衣 壳含有与异源AAV或非AAV衣壳蛋白(或其片段)融合的经单现突变校正的AAV衣壳 的一个或多个片段。这些人造衣壳蛋白选自经单现突变校正的衣壳的非连续部分 或选自其他AAV衣壳。这些改变的目的是为了增加表达、产量和/或改善选定表 达系统中的纯化，或为了其他目的(例如：改变趋性或修改中和抗体表位)。
本文所描述的载体例如质粒可用于各种目的，但特别适用于产生含有衣壳的rAAV，所述衣壳包含AAV序列或其片段。本文详细描述了这些载体，包括rAAV、 它们的元件、构建体和应用。
在一方面，本发明提供了一种产生具有本发明新AAV衣壳的重组腺相关病毒(AAV)的方法。该方法涉及培养宿主细胞，该宿主细胞含有如本文所定义的编码本 发明新AAV衣壳蛋白或其片段的核酸序列；功能性rep基因；至少由AAV反向末端 重复(ITR)和转基因组成的小基因；与足够的辅助功能因子以将小基因包装进AAV 衣壳蛋白。
在宿主细胞内培养将AAV小基因包装进AAV衣壳所必需的成分可以瞬时性地 (intranse)提供给宿主细胞。或者，由已经用本领域技术人员已知的方法改造而含 有一种或多种必需成分的稳定宿主细胞来提供一种或多种必需成分(例如：小基 因、rep序列、cap序列和/或辅助因子功能)。更适宜的是，这种稳定的宿主细胞 含有在诱导型启动子控制下的所需成分。然而，必需成分也可在组成型启动子的 控制下。在关于适合与转基因联用的调节元件的讨论中，本文提供了合适的诱导 型和组成型启动子的实例。或者，选定的稳定宿主细胞可含有在组成型启动子控 制下的选定成分和在一个或多个诱导型启动子控制下的其他选定成分。例如：可 由293细胞(含有在组成型启动子控制下的E1辅助因子)制造稳定的宿主细胞，但所 述稳定的宿主细胞含有在诱导型启动子控制下的rep和/或cap蛋白。本领域技术 人员也可制备其他稳定的宿主细胞。
产生本发明的rAAV所需的小基因、rep序列、cap序列和辅助因子可以各种能 够传递所带序列的遗传元件的形式递送至包装宿主细胞。选定的遗传元件可通过 任何适当的方法，包括本文所述的方法来递送。用于构建本发明这一方面的实施 方案的方法是核酸操作(包括遗传工程、重组工程与合成技术)领域的技术人员已 知的。参见，例如Sambrook等人，分子克隆：实验室手册(Molecular Cloning：A Laboratory Manual)，冷泉港出版社，冷泉港，纽约。类似地，产生AAV病毒粒子 的方法也是众所周知的，并且适当方法的选择不限制本发明。参见，例如：K.Fisher 等人，J.Virol.，70：520-532(1993)与美国专利号5,478,745。
除非另有规定，本文所述的AAV ITR与其他选定AAV成分可容易地选自任一 AAV，所述AVV包括但不限于：AAV1、AAV2、AAV3、AAV4、AAV5、AAV6、AAV7、 AAV9和本发明的其他新AAV序列。可使用本领域技术人员已知的技术容易地从AAV 序列中分离这些ITR或其他AAV成分。所述AAV可分离获得或得自学术、商业或公 共来源(例如：美国典型培养物保藏中心(ATCC)，Manassas，VA)。或者，所述AAV 序列可参考例如文献或数据库(例如，
Figure BDA0001170764950000121
等)中的已公开序列通过 合成或其他适当的方法获得。
A、小基因
小基因至少由转基因及其调节序列和5’和3’反向末端重复(ITR)组成。在一个理想的实施方案中，使用了AAV血清型2的ITR。然而，也可选择其他适当来源的ITR 。正是该小基因将被包装进衣壳蛋白并递送至选定的宿主细胞。
1.转基因
转基因是编码感兴趣的多肽、蛋白质或其他产物，并与其侧翼的载体序列异 源的核酸序列。核酸编码序列以允许转基因在宿主细胞中转录、翻译和/或表达 的方式操作性地与调节组件相连。
转基因序列的组成取决于所得到的载体的用途。例如：一类转基因序列包含 报道序列，该序列在表达后产生可检测的信号。这种报道序列包括但不限于编码 以下物质的DNA序列：β-内酰胺酶、β-半乳糖苷酶(LacZ)、碱性磷酸酶、胸腺激酶、 绿色荧光蛋白(GFP)、增强型GFP(EGFP)、氯霉素乙酰转移酶(CAT)、荧光素酶、膜 结合蛋白(如CD2、CD4、CD8)、流感血凝素蛋白和本领域熟知的存在高亲和力抗 体或可通过常规方法产生所述抗体的其他物质，以及含有膜结合蛋白的融合蛋白， 该膜结合蛋白适当地与血凝素或Myc等物质的抗原标记区融合。
当这些编码序列与驱动其表达的调节元件相关联时，可提供由常规方法检测 的信号，所述常规方法包括酶法、放射显影法、比色法、荧光法或其他光谱测定、 荧光激活细胞分选测定与免疫测定，包括酶联免疫吸附测定(ELISA)、放射性免疫 测定(RIA)和免疫组织化学。例如：当标记序列是LacZ基因时，通过测定β-半乳糖 苷酶的活性来检测携带信号的载体的存在。当转基因是绿色荧光蛋白或荧光素酶 时，携带信号的载体可用光度计通过颜色或光的产生来观测。
然而，理想地，转基因是编码具有生物或医药用途的产物的非标记序列，所 述产物例如蛋白质、肽、RNA、酶、显性阴性突变体或催化性RNA。理想的RNA分 子包括tRNA、dsRNA、核糖体RNA、催化性RNA、siRNA、小发夹RNA、反式剪接RNA 和反义RNA。有用的RNA序列的一个例子是抑制或消除靶核酸序列在经处理的动物 中表达的序列。通常，合适的靶序列包括肿瘤靶点和病毒疾病。例如后文免疫原 部分所述的肿瘤靶点和病毒。
转基因可用于校正或减少基因缺陷，包括正常基因的表达低于正常水平的缺 陷或功能基因产物不表达的缺陷。或者，转基因可为细胞提供本来不在该细胞类 型或该宿主中表达的产物。转基因序列的优选类型编码在宿主细胞中表达的治疗 性蛋白质或多肽。本发明进一步包括使用多种转基因。在某些情况下，可采用不 同的转基因编码一个蛋白质的各个亚基，或编码不同的肽或蛋白质。当编码蛋白 质亚基的DNA很大时这尤其适合，所述蛋白质例如免疫球蛋白、血小板衍生的生 长因子或抗肌萎缩蛋白。为使细胞产生多亚基蛋白质，用各自含有各不同亚基的 重组病毒感染细胞。或者，蛋白质的不同亚基可由同一转基因编码。在这种情况 下，单个转基因包含编码所有亚基的DNA，而各亚基的DNA由内部核糖体进入位 点(IRES)隔开。当编码每个亚基的DNA较小时，例如编码亚基的DNA与IRES的总体积小于5千碱基对(5kb)时，这尤其适合。作为IRES的替代，DNA可用编码在翻译后 阶段自我切割的2A肽的序列隔开。参见，例如：M.L.Donnelly等人，J.Gen.Virol .，78(第一部分)：13-21(1997年1月)；Furler，S.等人，Gene Ther.，8(11)：864-873(2001 年6月)；Klump H.等人，Gene Ther.，8(10)：811-817(2001年5月)。该2A肽明显小 于IRES，使得其非常适合用于当空间成为制约因素的时候。更常见的是，当转基 因较大、由多个亚基组成、或两个转基因共递送时，允许共用携带所需转基因或 亚基的rAAV以使得它们在体内多联化形成单一的载体基因组。在这种实施方案中， 第一AAV可携带表达一个转基因的表达盒，第二AAV可携带用于在宿主细胞中共表 达的不同转基因的表达盒。然而，选定的转基因可编码任何生物活性产物或其他 产物，例如：研究所需的产物。
本领域技术人员可容易地选择适当的转基因。转基因的选择不限制本发明。
2.调节元件
除了以上就小基因而言的主要元件以外，载体还包含常规控制元件，所述常 规控制元件以允许转基因在以下所述细胞中转录、翻译和/或表达的方式操作性 地与转基因相连，所述细胞为本发明产生的质粒载体转染或病毒所感染。本文的 “操作性相连”的序列包括与感兴趣的基因毗连的表达控制序列和以反式(in trans) 起作用或在一定距离开外控制感兴趣基因的表达的控制序列。
表达控制序列包括适宜的转录起始子、终止子、启动子和增强子序列；有效 的RNA加工信号，例如剪接和聚腺苷酸化(polyA)信号；稳定细胞质mRNA的序列； 增强翻译效率的序列(即：Kozak共有序列)；增强蛋白质稳定性的序列；以及在需 要时增强编码产物分泌的序列。许多表达控制序列，包括天然的、组成型的、诱 导型的和/或组织特异性的启动子是本领域已知并可利用的。
组成型启动子的例子包括但不限于：逆转录病毒Rous肉瘤病毒(RSV)LTR启动 子(任选连有RSV增强子)、巨细胞病毒(CMV)启动子(任选连有CMV增强子)[参见， 例如：Boshart等人，Cell，41：521-530(1985)]、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)启动子和EFl启动子(Invitrogen)。诱 导型启动子能调节基因表达，并可由外源提供的化合物、环境因素(例如温度)、 或特定生理状态调节，所述状态例如例如急性期、细胞的特定分化状态，或仅在 正在复制的细胞中起效。诱导型启动子和可诱导系统可从多种商业来源获得，包 括但不限于Invitrogen、Clontech和Ariad。已知的还有许多其他系统，可由本领域 技术人员容易地选择。受外源化合物调节的诱导型启动子的实例包括锌-诱导的金 属硫蛋白(MT)启动子、地塞米松(Dex)-诱导的小鼠乳腺肿瘤病毒(MMTV)启动子、 T7聚合酶启动子系统[国际专利公开号WO 98/10088]、蜕皮素昆虫启动子[No等 人，Proc.Natl.Acad.Sci.美国，93：3346-3351(1996)]、四环素阻抑系统[Gossen 等人，Proc.Natl.Acad.Sci.美国，89：5547-5551(1992)]、四环素诱导系统[Gossen 等人，Science，268：1766-1769(1996)，也参见Harvey等人，Curr.Opin.Chem. Biol.，2：512-518(1998)]、RU486-诱导系统[Wang等人，Nat.Biotech.，15： 239-243(1997)与Wang等人，GeneTher.，4：432-441(1997)]和雷帕霉素-诱导系统 [Magari等人，J.Clin.Invest.，100：2856-2872(1997)]。可用于本发明的其他诱导 型启动子类型是由特定的生理状态调节的那些，所述状态例如温度、急性期、细 胞的特定分化状态，或仅在正在复制的细胞中起效。
在另一个实施方案中使用了转基因的天然启动子。当需要转基因的表达模拟 天然表达时，可优选天然启动子。当转基因的表达必须暂时性或发展性方式调节、 或以组织特异性的方式调节或响应特定的转录刺激时，可使用天然启动子。在另 外的实施方案中，也可使用其他天然表达控制元件，例如增强子元件、聚腺苷酸 化位点或Kozak共有序列以模拟天然表达。
转基因的另一实施方案包含操作性连接于组织特异性启动子的基因。例如， 如果需要在骨骼肌中表达，应该使用在肌肉中有活性的启动子。这包括编码以下 产物的基因的启动子：骨骼β-肌动蛋白、肌球蛋白轻链2A、抗肌萎缩蛋白、肌肉 肌酸激酶以及活性高于天然启动子的合成肌肉启动子(参见：Li等人，Nat.Biotech .，17：241-245(1999))。已知的组织特异性启动子的实例有肝特异性的(白蛋白， Miyatake等人，J.Virol.，71：5124-32(1997)；乙肝病毒核心启动子，Sandig等人， Gene Ther.，3：1002-9(1996)：α-胎蛋白(AFP)，Arbuthnot等人，Hum.GeneTher .，7：1503-14(1996))、骨的骨钙蛋白(Stein等人，Mol.Biol.Rep.，24：185-96(1997)) ；骨唾液蛋白(Chen等人，J.Bone Miner.Res.，11：654-64(1996))、淋巴细胞特异 性的(CD2，Hansal等人，J.Immunol.161：1063-8(1998)；免疫球蛋白重链；T细胞 受体链)、神经元特异性的(例如神经元-特异性烯醇酶(NSE)启动子(Andersen等人， Cell.Mol.Neurobiol.，13：503-15(1993))、神经丝轻链基因(Piccioli等人，Proc .Natl.Acad.Sci.，美国，88：5611-5(1991))，以及神经元-特异性vgf基因(Piccioli 等人，Neuron，15：373-84(1995)))等。
任选地，携带有治疗用途的转基因的质粒还可含有可选择标记基因或报道基 因，例如编码遗传霉素抗性、潮霉素抗性或嘌呤霉素(purimycin)抗性等的序列。 这种可选择的报道基因或标记基因(优选位于有待本发明方法拯救的病毒基因组 之外)，例如氨苄青霉素抗性，可用来指示细菌细胞中存在质粒。质粒的其他成分 可包括复制起点。可通过常规方法选择这些和其他启动子与载体元件，许多这种 序列可获得[参见，例如：Sambrook等人，以及本文引用的参考文献]。
为援引方便，转基因、启动子/增强子与5'和3'AAV ITR的组合在此称为“小基因”。鉴于本发明的教导，凭借常规技术即可设计这种小基因。
3.将小基因递送至包装宿主细胞
可用任何递送至宿主细胞的适当载体例如质粒来携带小基因。用于本发明的 质粒可改造为适合于在原核细胞、哺乳动物细胞或这二种细胞中复制和整合(任选) 的质粒。这些质粒(或其他携带5'AAV ITR-异源分子-3'AAV ITR的载体)含有允许小基 因在真核细胞和/或原核细胞中复制的序列和用于这些系统的选择标记。可选择 标记基因或报道基因可包括编码遗传霉素抗性、潮霉素抗性或嘌呤霉素抗性等的 序列。这些质粒还可含有可用来指示细菌细胞中存在载体的某些可选择报道基因 或标记基因，例如氨苄青霉素抗性。质粒的其他成分可包括复制起点和扩增子， 例如使用Epstein Barr病毒核抗原的扩增子系统。该扩增子系统或其他类似的扩增 子成分允许细胞中高拷贝附加型复制。携带小基因的分子优选转染入其可暂时存 在的细胞中。或者，小基因(携带5'AAV ITR-异源分子-3'AAVITR)可稳定地整合进宿 主细胞的基因组，或进入染色体或作为附加体。在某些实施方案中，小基因可以 任选地以头-对-头、头-对-尾或尾-对-尾的多联体形式多拷贝存在。合适的转染技 术是已知的，并可容易地用于将小基因递送至宿主细胞。
通常，当通过转染递送含有小基因的载体时，通常将约5μg-100μg DNA、约 10μg-50μg DNA递送约1×104-1×1013个细胞或约1×105个细胞。然而，考虑到诸 如所选择的载体、递送方法和所选择的宿主细胞等因素，本领域技术人员可调整 载体DNA量与宿主细胞之比。
B.Rep与Cap序列
除了小基因以外，宿主细胞还含有在宿主细胞中驱动本发明的新AAV衣壳蛋 白(或含有其片段的衣壳蛋白)表达的序列和与小基因中的AAV ITR相同来源或来自 交叉互补来源的rep序列。AAV cap和rep序列可彼此独立地由前述AAV源获得，并 可以前述本领域人员已知的任何方式引入宿主细胞。此外，在进行AAV载体假型 包装时，可用不同的AAV来源(例如：AAV1、AAV2、AAV3、AAV4、AAV5、AAV6、 AAV7、AAV8、AAV9)提供编码各种主要rep蛋白的序列。例如：rep78/68序列得 自AAV2，而rep52/40序列得自AAV8。
在一个实施方案中，宿主细胞稳定地含有在合适的启动子(例如前文所述)控 制下的衣壳蛋白。在该实施方案中，衣壳蛋白最好在诱导型启动子的控制下表达 。在另一个实施方案中，衣壳蛋白以转入方式(in trans)提供至宿主细胞。当以转 入方式递送至宿主细胞时，衣壳蛋白可通过含有指导选定衣壳蛋白在宿主细胞中 表达所需序列的质粒递送。当以转入方式递送至宿主细胞时，携带衣壳蛋白的质 粒最好还携带包装rAAV所需的其他序列，例如rep序列。
在另一个实施方案中，宿主细胞稳定地含有在合适的启动子(如前文所述)控 制下的rep序列。在该实施方案中，主要rep蛋白最好在诱导型启动子的控制下表 达。在另一个实施方案中，rep蛋白以转入方式(in trans)提供至宿主细胞。当以转 入方式递送至宿主细胞时，rep蛋白可通过含有指导选定的rep蛋白在宿主细胞中 表达所需序列的质粒递送。当以转入方式递送至宿主细胞时，携带衣壳蛋白的质 粒也最好携带包装rAAV所需的其他序列，例如rep和cap序列。
因此，在一个实施方案中，rep和cap序列可以位于一个核酸分子上转染入宿 主细胞，并且作为附加体稳定地存在于细胞中。在另一个实施方案中，rep和cap 序列稳定地整合进细胞的染色体。在另一个实施方案中，rep和cap序列在宿主细 胞中瞬时表达。例如，用于这种转染的有用核酸分子从5’到3’含有启动子、插在启 动子与rep基因序列起始位点之间可选的间隔子、AAV rep基因序列和AAV cap基因 序列。
任选地，rep和/或cap序列可提供于载体上，该载体含有待引入宿主细胞的 其他DNA序列。例如：载体可含有包含小基因的rAAV构建体。载体可含有一个或 多个编码辅助因子功能例如腺病毒蛋白E1、E2a和E4ORF6的基因与VAI RNA的基因 。
用于该构建体的启动子优选本领域技术人员已知的或前文所述的特征组成 型、诱导型或天然启动子。在一个实施方案中，使用AAV P5启动子序列。选择AAV 来提供这些序列不是对本发明的限制。
在另一个优选的实施方案中，rep的启动子是诱导型启动子，例如前文就转基 因调节元件所述的那些。Rep表达的优选的启动子之一是T7启动子。用包含由T7 启动子调节的rep基因和cap基因的载体转染或转化组成性或诱导性表达T7聚合酶 的细胞。参见1998年3月12日公开的国际专利公开号W0 98/10088。
在设计载体中，间隔子是可选元件。间隔子是插在启动子和rep基因的ATG起 始位点间的DNA序列。间隔子可具有任何所需的设计；即，它可是随机的核苷酸 序列，或者可编码一个基因产物，例如标记基因。间隔子可含有通常包括起始/ 终止和polyA位点的基因。间隔子可以是来自原核生物或真核生物的非编码DNA序 列、重复非编码序列、无转录控制的编码序列或有转录控制的编码序列。间隔子 序列的两个典型来源是噬菌体梯序列或酵母梯序列，二者可购自例如Gibco或 Invitrogen等。间隔子可是任何大小的，只要足以降低rep78和rep68基因产物的表 达，使rep52、rep40和cap基因产物的表达处于正常水平。因此，间隔子的长度范 围约为l0bp-10.0kbp，优选约100bp-8.0kbp。为减少重组的可能性，间隔子长度 优选小于2kbp；然而，本发明不限于此。
虽然提供rep和cap的分子可能瞬时(即通过转染)存在于宿主细胞中，但优选 rep和cap蛋白之一或二者与控制其表达的启动子在宿主细胞中稳定地表达，例如 作为附加体或通过整合进宿主细胞染色体。用于构建本发明这方面内容的实施方 案的方法是常规遗传工程或重组工程技术，例如前文参考文献所述的技术。虽然 本说明书提供了具体的构建体的说明性实例，但本领域技术人员可使用本文提供 的信息来选择间隔子、P5启动子和其他元件(包括至少一个翻译起始和终止信号) 和任选加入的聚腺苷酸化位点，从而可选择和设计其他合适的构建体。
在本发明的另一个实施方案中，可由宿主细胞稳定地提供rep或cap蛋白。
C.辅助因子功能
为包装本发明的rAAV，包装宿主细胞还需要辅助因子功能。任选地，这些功 能可由疱疹病毒提供。所需的辅助功能物最好分别由人或非人灵长类腺病毒源提 供，例如前文所述的和/或得自各种来源的(包括美国典型培养物保藏中心(ATCC)， Manassas，VA(美国))。在一个目前优选的实施方案中，向宿主细胞提供和/或宿 主细胞含有E1a基因产物、E1b基因产物、E2a基因产物和/或E4ORF6基因产物。 宿主细胞可含有其他腺病毒基因，例如VAI RNA，但这些基因不是必需的。在优选 的实施方案中，宿主细胞中不存在其他腺病毒基因或基因功能。
“表达E1a基因产物的腺病毒DNA”表示编码E1a或其功能性部分的各种腺病毒 序列。表达E2a基因产物的腺病毒DNA和表达E4 0RF6基因产物的腺病毒DNA的定义 类似。腺病毒基因或其功能部分的各等位基因或其他修饰形式也包括在内。所述 修饰既包括借助常规遗传工程或诱变技术特地引入从而以某种方式增强腺病毒功 能的那些，也包括天然存在的等位变体。这些用来通过DNA操作获得腺病毒基因 功能的修饰和方法是本领域技术人员已知的。
腺病毒E1a、E1b、E2a和/或E4ORF6基因产物以及各种其他需要的辅助因子 功能可使用各种使其在细胞中表达的方法提供。各条编码这些产物的序列可各自 位于单独的载体上，或者一个或多个基因可位于同一载体上。载体可以是本领域 已知的或前文所述的各种载体，包括质粒、粘粒和病毒。载体可通过本领域已知 或前文所述的各种方法引入宿主细胞，所述方法包括转染、感染、电穿孔、脂质 体递送、膜融合技术、高速DNA-包被小球、病毒感染与原生质体融合等。一个或 多个腺病毒基因可稳定地整合入宿主细胞基因组，作为附加体稳定表达，或者瞬 时表达。基因产物可全部瞬时表达，包含在附加体上或稳定整合；或者，一些基 因产物可稳定地表达，而另一些瞬时表达。此外，各腺病毒基因的启动子可彼此 独立地选自组成型启动子、诱导型启动子或天然腺病毒启动子。启动子可由生物 体或细胞的特定生理状态调节(即，分化状态或复制或静息细胞)或由其他方法例 如外源添加因子调节。
D.宿主细胞和包装细胞系
宿主细胞本身可选自各种生物体，包括原核(例如：细菌)细胞和真核细胞， 包括昆虫细胞、酵母细胞和哺乳动物细胞。特别理想的宿主细胞选自特征哺乳动 物种类，包括，不限于以下细胞：A549、WEHI、3T3、10T1/2、BHK、MDCK、 COS1、COS7、BSCl、BSC40、BMT10、VERO、W138、HeLa、293细胞(表达功能性 腺病毒E1)、Saos、C2C12、L细胞、HT1080、HepG2和来源于哺乳动物(包括人、猴、 小鼠、大鼠、兔子和仓鼠)的初级成纤维细胞、肝细胞和成肌细胞。选择细胞的哺 乳动物来源和哺乳动物细胞的类型(即成纤维细胞、肝细胞、肿瘤细胞等)不限制 本发明。对所使用细胞的要求是：它不携带任何除E1、E2a和/或E4 0RF6以外的腺病毒基因；它不含有在rAAV产生过程中可导致污染病毒的同源重组的任何其他 病毒基因；并且，它能被DNA感染或转染并表达所转染的DNA。在优选的实施方 案中，宿主细胞是在包含稳定转染的rep和cap的细胞。
用于本发明的宿主细胞之一是用编码rep和cap的序列稳定转化，并用腺病毒 E1、E2a和E4 0RF6DNA和携带有前文所述小基因的构建体转染的宿主细胞。也可 类似地使用稳定的rep和/或cap表达细胞系，例如B-50(国际专利申请公开号W0 99/15685)，或美国专利号5,658,785所述的细胞系。另一种理想的宿主细胞含有 表达E4ORF6所需的基本腺病毒DNA。使用本发明的新经单现突变校正的AAV cap 序列还可构建出其他细胞系。
本发明制备宿主细胞涉及诸如装配选定的DNA序列等技术。可使用常规技术 实现这种装配。这种技术包括公知的且描述于前文引用的Sambrook等人的著作中 的cDNA和基因组克隆、使用腺病毒和AAV基因组的重叠寡核苷酸序列，结合聚合 酶链式反应、合成方法以及提供所需核苷酸序列的其他合适方法。
也可使用技术人员已知和本说明书中讨论的技术将这些分子(如质粒或病毒) 引入宿主细胞。在优选的实施方案中，使用标准转染技术，例如：CaP04转染或电 穿孔，和/或用杂交腺病毒/AAV载体感染细胞系，所述细胞系例如人胚胎肾细 胞系HEK293(一种人肾细胞系，含功能性腺病毒E1基因，该基因提供反式作用的E1 蛋白)。
本领域技术人员易于理解的是，本发明的新AAV序列可容易地经调整而适用 在上述及其他表达载体系统中用于体外、离体或体内的基因递送。类似地，本领 域技术人员可容易地选择本发明的其他AAV基因组片段用于各种rAAV和非rAAV载 体系统。这些载体系统包括例如：慢病毒、逆转录病毒、痘病毒、牛痘病毒和腺 病毒系统等。这些载体系统的选择不限制本发明。
因此，本发明进一步提供了使用本发明的新AAV的核酸与氨基酸序列产生的 载体。这种载体可用于多种目的，包括递送治疗性分子和用在疫苗给药方案 (vaccineregimens)中。含有本发明的新AAV衣壳的重组AAV对递送治疗性分子特别 理想。含有本发明的新AAV序列的这些或其他载体构建体可用于疫苗给药方案， 例如：用于共同递送细胞因子，或用于递送免疫原本身。
IV.重组病毒及其应用
本领域技术人员可使用本文所述的技术来产生rAAV，该rAAV具有本发明AAV 的衣壳或其衣壳含有本发明AAV的一个或多个片段。在一个实施方案中，使用来 自经单现突变校正的AAV的全长衣壳。
A.病毒的递送
另一方面，本发明提供了一种将转基因递送至宿主的方法，该方法涉及利用 本发明经单现突变校正的AAV(或其功能性片段)产生的重组病毒载体转染或感染 所选宿主细胞。用于递送的方法是本领域技术人员公知的，并不限制本发明。
在一个理想的实施方案中，本发明提供了一种用于AAV-介导递送转基因至宿 主的方法。该方法涉及利用含有所选转基因和修正衣壳蛋白的重组病毒载体转染 或感染所选宿主细胞，该转基因在指导其表达的序列的控制下。
任选地，来自宿主的样品可首先测定其是否含有所选AAV源(例如：某血清型) 的抗体。用于检测中和抗体的各种测定方式已为本领域技术人员所熟知。这种测 定的选择不限制本发明。参见，例如：Fisher等人，Nature Med.，3(3)：306-312(1997 年3月)和W.C.Manning等人，Human Gene Therapy，9：477-485(1998年3月1日) 。该测定的结果，例如没有某衣壳来源的特异性中和抗体，可用于确定哪种含有 特定来源的衣壳蛋白的AAV载体是递送所优选的。
该方法的一方面，可在递送具有本发明AAV衣壳蛋白的载体之前或之后递送 具有另一不同AAV衣壳蛋白的载体。因此，通过rAAV载体的基因递送可用于重复 地将基因递送至所选定的宿主细胞中。理想地，在后给予的rAAV载体携带与第一 rAAV载体中相同的转基因，但在后给予的载体含有的衣壳蛋白的来源不同于第一 载体(并且优选不同的血清型)。例如：如果第一载体具有经单现突变校正的衣壳 蛋白，在后给予的载体可具有选自其他AAV的衣壳蛋白，例如可以是另一血清型 或另一分化体的AAV。
任选地，多个rAAV载体可通过共同给予多个rAAV载体用于递送大的转基因或 多个转基因，在体内多联化成单个载体基因组。在这种实施方案中，第一AAV可 携带表达单个转基因(或其亚基)的表达盒，第二AAV可携带在宿主细胞中共表达的 表达第二转基因(或不同亚基)的表达盒。第一AAV可携带多顺反子构建体的第一部 分(例如：启动子和转基因，或亚基)的表达盒，第二AAV可携带多顺反子构建体的 第二部分(例如：转基因或亚基和polyA序列)的表达盒。多顺反子构建体的这两个 部分在体内多联化成共表达由第一和第二AAV递送的转基因的单个载体基因组。 在这种实施方案中，携带第一表达盒的rAAV载体和携带第二表达盒的rAAV载体可 以包含在单个药物组合物中来递送。在其他实施方案中，两个或多个rAAV载体以 分开的药物组合物来递送，这些药物组合物可基本上同时给药或略有先后。
上述重组载体可按照公开的方法递送至宿主细胞中。可将rAAV，优选悬浮在 生理相容载体中的rAAV，给予人或非人哺乳动物患者。本领域技术人员可依据病 毒递送所针对的适应症容易地选择适当的载体。例如，适当的载体包括可用各种 缓冲液配制的盐水(例如：磷酸缓冲盐水)。其他的载体例子包括无菌盐水、乳糖、 蔗糖、磷酸钙、明胶、葡萄糖、琼脂、果胶、花生油、芝麻油和水。载体的选择 不限制本发明。
任选地，除rAAV和载体以外，本发明的组合物还可含有其他常规药物组分， 例如防腐剂或化学稳定剂。适当的防腐剂例如氯代丁醇、山梨酸钾、山梨酸、二 氧化硫、没食子酸丙酯、对羟基苯甲酸酯类、乙基香草醛、甘油、苯酚与对氯苯 酚。适当的化学稳定剂包括明胶和白蛋白。
载体的给予量应满足转染细胞所需并应提供足够的基因传送和表达水平以 提供疗效而无副作用，或有医学上可接受的生理作用，这可由医学领域技术人员 确定。常规的和药学上可接受的给药途径包括但不限于：直接递送至目标器官(例 如，肝(任选经肝动脉)或肺)、口服、吸入、鼻内、气管内、动脉内、眼内、静脉 内、肌肉内、皮下、真皮内和其他胃肠外给药途径。如果需要，可多种给药途径 联用。
病毒载体的剂量主要取决于以下因素，例如治疗的病症、患者的年龄、体重 和健康状况，因此可依患者而改变。例如，病毒载体的人用治疗有效剂量一般约 为含有浓度约1×109-1×1016个基因组病毒载体的0.1mL-100mL溶液。递送至大器 官(例如：肝、肌肉、心脏和肺)的优选的人用剂量可约为5×1010-5×1013个AAV基 因组/kg，体积约为1-100mL。递送至眼的优选剂量约为5×109-5×1012份基因组 拷贝，体积约为0.1mL-1mL。可调整剂量以平衡副作用和疗效，并且这种剂量可根 据重组载体的具体治疗性用途而改变。可监测转基因的表达水平来确定给药频率， 以获得病毒载体，优选含有小基因的AAV载体。任选地，可按照类似于就治疗性 目所述的给药方案用本发明的组合物来免疫接种。
后文提供了用本发明的含AAV载体进行递送的治疗性产物和免疫原性产物的 实例。这些载体可用于本文所述的各种治疗性或接种方案。此外，按照治疗性和 /或接种方案所需，这些载体可联合一种或多种其他载体或活性成分用于递送。
B.治疗性转基因
转基因编码的有用的治疗性产物包括激素与生长因子和分化因子，包括但不 限于：胰岛素、胰高血糖素、生长激素(GH)、甲状旁腺激素(PTH)、生长激素释放 因子(GRF)、卵泡刺激素(FSH)、黄体激素(LH)、人绒毛膜促性腺激素(hCG)、血管内 皮生长因子(VEGF)、促血管生成素、血管抑制素、粒细胞集落刺激因子(GCSF)、促 红细胞生产素(EPO)、结缔组织生长因子(CTGF)、碱性成纤维细胞生长因子(bFGF)、 酸性成纤维细胞生长因子(aFGF)、表皮生长因子(EGF)、血小板衍生的生长因子 (PDGF)、胰岛素生长因子I和II(IGF-I和IGF-II)、转化生长因子α超家族中的任一个(包 括TGFα、活化素、抑制素)、或骨形态发生蛋白(BMP)BMP1-15中的任一个、生长 因子中的调蛋白/神经调节蛋白/ARIA/neu分化因子(NDF)家族的任一个、神经 生长因子(NGF)、脑源性神经营养因子(BDNF)、神经营养蛋白NT-3和NT-4/5、睫状 神经营养因子(CNTF)、胶质细胞系衍生神经营养因子(GDNF)、neurturin、聚集蛋 白、脑信号蛋白/瓦解蛋白家族的任一个、导蛋白-1和导蛋白-2、肝细胞生长因 子(HGF)、肝配蛋白、头蛋白、sonic hedgehog蛋白和酪氨酸羟化酶。
其他有用的转基因产物包括调节免疫系统的蛋白质，包括但不限于：细胞因 子和淋巴因子，例如血小板生成素(TPO)、白介素(IL)IL-1到IL-25(包括，例如：IL-2、 IL-4、IL-12和IL-18)、单核细胞化学诱导蛋白、白血病抑制因子、粒细胞-巨噬细胞 集落刺激因子、Fas配体、肿瘤坏死因子α和β、干扰素α、β和γ、干细胞因子、flk-2 /flt3配体。免疫系统产生的基因产物也可用于本发明。这些产物包括但不限于： 免疫球蛋白IgG、IgM、IgA、IgD和IgE、嵌合免疫球蛋白、人源化抗体、单链抗体、 T细胞受体、嵌合T细胞受体、单链T细胞受体、I类和Ⅱ类MHC分子，以及经改造 的免疫球蛋白和MHC分子。有用的基因产物还包括补体调节蛋白质，例如补体调 节蛋白、膜辅因子蛋白(MCP)、衰变加速因子(DAF)、CR1、CF2和CD59。
其他有用的基因产物包括激素受体、生长因子、细胞因子、淋巴因子、调节 蛋白质和免疫系统蛋白质的任一种。本发明包括胆固醇调节和/或脂质调节的受 体，包括低密度脂蛋白(LDL)受体、高密度脂蛋白(HDL)受体、极低密度脂蛋白(VLDL) 受体和清除受体。本发明也包括以下基因产物：例如类固醇激素受体超家族的成 员，包括糖皮质激素受体和雌激素受体、维生素D受体和其他核受体。此外，有 用的基因产物包括转录因子，例如jun、fos、max、mad、血清效应因子(SRF)、AP-1、 AP2、myb、MyoD和肌细胞生成蛋白、含有蛋白质的ETS-盒、TFE3、E2F、ATFl、 ATF2、ATF3、ATF4、ZF5、NFAT、CREB、HNF-4、C/EBP、SP1、CCAAT-盒结合蛋白、 干扰素调节因子(IRF-1)、Wilms肿瘤蛋白、ETS-结合蛋白、STAT、GATA-盒结合蛋白， 例如GATA-3和翼状螺旋蛋白的叉头蛋白家族。
其他有用的基因产物包括氨甲酰磷酸合成酶I、鸟氨酸转氨甲酰酶、精氨基琥 珀酸合成酶、精氨基琥珀酸裂合酶、精氨酸酶、延胡索酰乙酰乙酸水解酶、苯丙 氨酸羟化酶、α-1抗胰蛋白酶、葡萄糖-6-磷酸酶、胆色素原脱氨酶、胱硫醚β-合成 酶、支链酮酸脱羧酶、白蛋白、异戊酰-CoA脱氢酶、丙酰-CoA羧化酶、甲基丙二 酰CoA变位酶、戊二酰-CoA脱氢酶、胰岛素、β-葡糖苷酶、丙酮酸羧酸盐、肝磷酸 化酶、磷酸化酶激酶、甘氨酸脱羧酶、H-蛋白、T-蛋白、囊性纤维化跨膜传导调 节蛋白(CFTR)序列和抗肌萎缩蛋白基因产物[例如：小-或微-抗肌萎缩蛋白]。其他 有用的基因产物包括可用于酶活性缺乏所导致的各种病症例如可用于酶替代治疗 的酶。例如，含有甘露糖-6-磷酸的酶可用于治疗溶菌酶储存疾病(例如编码β-葡糖 醛酸糖苷酶(GUSB)的基因)。
其他有用的基因产物包括用于治疗血友病的产物，包括B型血友病(包括因子 IX)和A型血友病(包括因子VIII及其变体，例如异二聚体的轻链和重链和B-缺失结构 域；美国专利号6,200,560和美国专利号6,221,349)。因子VIII基因编码2351个氨基 酸，该蛋白具有六个结构域，从氨基向羧基端依次指定为A1-A2-B-A3-C1-C2[Wood 等人，Nature，312：330(1984)；Vehar等人，Nature，312：337(1984)；以及Toole 等人，Nature，342：337(1984)]。人因子VIII在细胞内经加工产生主要含有重链和 轻链的异二聚体，所述重链含有A1、A2和B结构域，所述轻链含有A3、C1和C2结 构域。单链多肽与异二聚体作为无活性的前体在血浆中循环，直至在A2和B结构 域之间被凝血酶切割而激活，由此释放出B结构域并形成由A1和A2结构域组成的 重链。该蛋白质激活的前凝血质形式不含B结构域。此外，在天然蛋白中，B结构 域之侧的两条多肽链(“a”和“b”)与二价钙阳离子结合。
在一些实施方案中，小基因含有编码10个氨基酸信号序列的因子VIII重链的前57个碱基对和人生长激素(hGH)聚腺苷酸化序列。在另一实施方案中，小基因进一 步含有A1和A2结构域，以及B结构域N-末端的5个氨基酸，和/或B结构域C-末端 的85个氨基酸，以及A3、C1和C2结构域。在另外的实施方案中，编码因子VIII重链 和轻链的核酸被编码B结构域的14个氨基酸的42个核酸隔开并包含在单个小基因 中[美国专利号6,200,560]。
本文使用的治疗上的有效量指可产生足够量的因子VIII以降低受试对象血液 凝结所需时间的AAV载体的量。通常，因子VIII水平低于正常水平的1％的严重血友 病患者的全血凝时间大于60分钟，而非血友病患者约为10分钟。
本发明不限于任何具体的因子VIII序列。已经分离和产生了许多因子VIII的天然和重组形式。因子VIII的天然形式和重组形式的实例见专利和科学文献，包括美 国专利号5,563,045；5,451,521；5,422,260；5,004,803；4,757,006；5,661,008； 5,789,203；5,681,746；5,595,886；5,045,455；5,668,108；5,633,150；5,693,499 ；5,587,310；5，171,844；5,149,637；5,112,950；4,886,876；国际专利公开号WO 94/11503，WO 87/07144，WO92/16557，WO 91/09122，W0 97/03195， W0 96/21035和WO 91/07490；欧洲专利申请号EP 0672 138，EP 0 270 618，EP 0 182 448，EP 0 162 067，EP 0 786 474，EP 0 533 862，EP 0506 757，EP 0 874 057， EP 0 795 021，EP 0 670 332，EP 0 500 734；EP 0 232 112和EP0 160 457；Sanberg 等人，世界血友病联合会第20届国际会议(XXth Int.Congress ofthe World Fed.Of Hemophilia)，(1992)和Lind等人，Eur.J.Biochem.，232：19(1995)。
编码上述因子VIII的核酸序列可使用重组方法获得或从已知包含该序列的载 体得到。此外，也可使用标准技术直接从含有该序列的细胞和组织中分离所需序 列，所述标准技术例如酚提取与cDNA或基因组DNA的PCR[参见，例如：Sambrook 等人]。除了克隆以外，核苷酸序列也可合成产生。可用标准方法制备重叠的寡核 苷酸，从重叠的寡核苷酸装配成完整的编码序列中[参见，例如：Edge，Nature， 292：757(1981)；Nambari等人，Science，223：1299(1984)和Jay等人，J.Biol.Chem .，259：6311(1984)]。
此外，本发明不限于人因子VIII。实际上，本发明意在包括来自除人以外的动 物的因子VIII，所述动物包括但不限于宠物动物(例如：狗、猫和马)、牲畜(例如： 牛、山羊和绵羊)、实验室动物、海生动物、大型猫科动物(large cat)等。
AAV载体可含有编码因子VIII片段的核酸，该片段本身无生物活性，但当给予 受试对象时则能改善或恢复血凝时间。例如，如前所述，因子VIII蛋白含有两条多 肽链：由B结构域隔开的重链和轻链，B结构域将在加工过程中被切除。如本发明 所证明的，用因子VIII的重链和轻链共转导受体细胞导致生物活性因子VIII的表达 。由于大多数血友病患者仅在一条链(例如：重链或轻链)中含有突变或缺失，这 就有可能仅给予患者有缺陷的那条链来与另一条链互补。
其他有用的基因产物包括非天然存在的多肽，例如具有非天然存在的氨基酸 序列的嵌合或杂交多肽，所述非天然存在的氨基酸序列含有插入、缺失或氨基酸 取代。例如，经单链改造的免疫球蛋白可用在某些免疫低下患者中。其他类型的 非天然存在的基因序列包括反义分子和催化性核酸，例如核酶，可用于降低靶的 过度表达。
降低和/或调节基因表达对治疗以细胞过度增殖为特征的过度增殖性疾病， 例如癌症和银屑病，尤其理想。靶多肽包括，与正常细胞相比，仅在过度增殖细 胞中产生或在过度增殖细胞中以更高水平产生的多肽。靶抗原包括癌基因和易位 基因编码的多肽，所述癌基因编码的多肽例如myb、myc、fyn，所述易位基因编 码的多肽如bcr/abl、ras、src、P53、neu、trk和EGRF。除了作为靶抗原的癌基因 产物，用于抗癌治疗和保护性治疗方案的靶多肽包括B细胞淋巴瘤产生的抗体的可 变区和T细胞淋巴瘤的T细胞受体的可变区，在某些些实施方案中，它们也用作自 身免疫疾病的靶抗原。其他肿瘤相关多肽也可用作靶多肽，例如在肿瘤细胞中处 于较高水平的多肽，包括单克隆抗体17-lA所识别的多肽和叶酸结合多肽。
其他合适的治疗性多肽和蛋白质包括通过赋予抗自身免疫相关靶的广谱基 础保护性免疫应答来治疗患自身免疫疾病和紊乱的个体的多肽和蛋白，所述自身 免疫相关靶包括细胞受体和产生“自我”定向抗体的细胞。T细胞介导的自身免疫疾 病包括类风湿性关节炎(RA)、多发性硬化症(MS)、
Figure BDA0001170764950000261
氏综合征、结节病、胰 岛素依赖型糖尿病(IDDM)、自身免疫甲状腺炎、反应性关节炎、强直性脊柱炎、 硬皮病、多肌炎、皮肌炎、银屑病、脉管炎、韦格纳肉芽肿病、克罗恩病和溃疡 性结肠炎。这些疾病均以结合内源性抗原并引发自身免疫疾病相关炎性级联反应 的T细胞受体(TCR)为特征。
C.免疫原性转基因
本发明的AAV载体以避免产生针对包含于载体的AAV序列的免疫应答为宜。然 而，这些载体配制成使得载体携带的转基因得以表达从而诱导对选定抗原的免疫 应答。例如，为促进免疫应答，可由组成型启动子控制转基因的表达，如本文所 述将载体与佐剂组合，和/或可将载体引入退化组织中。
适当的免疫原性转基因的实例可包括选自各种病毒科的免疫原性转基因。需 要免疫应答来抵御的病毒科的实例包括：小RNA病毒科，其包括导致约50％普通感 冒病例的鼻病毒属；肠病毒属，其包括脊髓灰质炎病毒、柯萨奇病毒、艾柯病毒 和人肠病毒(例如甲肝病毒)；以及口疮病毒属，其主要在非人动物中导致口蹄疫 。在小RNA病毒科内，靶抗原包括VP1、VP2、VP3、VP4和VPG。其他病毒科包括 星状病毒和杯状病毒科。杯状病毒科包括视为流行性肠胃炎重要病因的诺瓦克组 病毒。另一种有望用于靶抗原在人或非人动物中诱导免疫应答的病毒科是披膜病 毒科，该科包括甲型病毒属，该甲型病毒属包括辛德毕斯病毒、罗斯河病毒、和 委内瑞拉、东部和西部马脑炎病毒和风疹病毒属，包括风疹病毒。黄病毒科包括 登革热、黄热、日本脑炎、圣路易斯脑炎和蜱传性脑炎病毒。其他靶抗原可从丙型肝炎或冠状病毒科产生，其中包括许多非人病毒，例如感染性支气管炎病毒(家 禽)、猪传染性胃肠病毒(猪)、猪凝血性脑脊髓炎病毒(猪)、猫感染性腹膜炎病毒 (猫)、猫肠冠状病毒(猫)、狗冠状病毒(狗)和可导致普通感冒和/或非-甲型、乙型 或丙型肝炎的人呼吸冠状病毒，该科病毒还可能是严重急性呼吸道综合症(SARS) 的病因。在冠状病毒科内，靶抗原包括E1(也称为M或基质蛋白)、E2(也称为S或刺 蛋白)、E3(也称为HE或血凝素-依尔替糖)、糖蛋白(并非所有冠状病毒中都有)或N(核 衣壳)。他抗原还可以是针对动脉炎病毒科和弹状病毒科的。弹状病毒科包括水疱 病毒属(例如：疱疹口炎病毒)和狂犬病病毒属(例如：狂犬病)。在弹状病毒科内， 适当的抗原可源于G蛋白或N蛋白。包括出血热病毒例如马尔堡和埃博拉病毒的丝 状病毒科可能是合适的抗原来源。副黏病毒科包括1型副流感病毒、3型副流感病 毒、3型牛副流感病毒、腮腺炎病毒(流行性腮腺炎病毒)、2型副流感病毒、4型副 流感病毒、新城疫病毒(小鸡)、牛瘟病毒、麻疹病毒(其包括麻疹和犬瘟热)，以及 肺病毒(其包括呼吸道合胞病毒)。流感病毒被分在正黏病毒科内，并且是抗原(例 如：HA蛋白、N1蛋白)的合适来源。布尼亚病毒科包括布尼亚病毒属(加利福尼亚 脑炎，拉克罗斯脑炎)、白蛉热病毒属(裂谷热)、汉坦病毒属(普马拉是hemahagin 热病毒)、内罗毕病毒属(内罗毕绵羊病)和各种未命名的银环蛇病毒(bungaviruse) 。沙粒病毒科提供抗LCM和拉沙热病毒的抗原来源。抗原的另一来源是博内病毒 科。呼肠孤病毒科包括呼肠孤病毒属、轮状病毒属(其导致儿童急性肠胃炎)、环 状病毒属和科罗拉多蜱热病毒属(科罗拉多蜱热病毒属、Lebombo病毒属(人)、马 变性脑病病毒属、蓝舌病病毒属)。逆转录病毒科包括致肿瘤RNA病毒亚科，该亚 科包括人和兽医疾病，例如猫白血病病毒、HTLVI和HTLVII、慢病毒亚科(包括HIV、 猿免疫缺陷病毒、猫免疫缺陷病毒、犬感染性贫血病毒和泡沫病毒亚科)。
就HIV和SIV而言，已经描述了许多合适的抗原，并可以容易地选择。合适的 HIV和SIV抗原的实例包括但不限于gag、pol、Vif、Vpx、VPR、Env、Tat和Rev蛋白， 及其各种片段。例如，适当的被膜(env)蛋白的片段包括，例如：gp41、gp140和 gp120。另外，已经描述了对于这些及其他HIV和SIV抗原的各种修饰。用于该用途 的合适抗原是本领域技术人员所知的。例如，可从其他蛋白中选择编码gag、pol、 Vif以及Vpr、Env、Tat和Rev的序列。参见，例如：在美国专利5,972,596中描述了 修饰的gag蛋白。同时参见，在D.H.Barouch等人，J.Virol.，75(5):2462-2467(2001 年3月)和R.R.Amara等人，Science，292:69-74(2001年4月6日)中所描述的HIV和SIV 蛋白。这些蛋白质或其亚基可经由多个载体或由单个载体单独或组合递送。
乳多空病毒科包括多瘤病毒亚科(BKU和JCU病毒)和乳头瘤病毒亚科(与癌症 或乳头瘤的恶性进展有关)。腺病毒科包括导致呼吸疾病和/或肠炎的病毒(EX、 AD7、ARD、O.B.)。细小病毒科包括猫细小病毒(猫肠炎)、猫全白细胞减少病病毒、 狗细小病毒和猪细小病毒科。疱疹病毒科包括疱疹病毒亚科，该亚科包括单纯疱 疹病毒属(HSVI、HSVII)、水痘病毒属(假狂犬病、水痘带状疱疹)；以及β疱疹病毒 亚科，该亚科包括巨细胞病毒属(HCMV，鼠巨细胞病毒属)；和γ疱疹病毒亚科， 该亚科包括淋巴潜伏病毒属、EBV(伯基特淋巴瘤)、人疱疹病毒6A、6B和7、卡波 西肉瘤相关疱疹病毒与弥猴疱疹病毒(B病毒)、传染性鼻气管炎病毒属、马雷克病 病毒属和细长病毒属。痘病毒科包括脊椎动物痘病毒亚科，包括正痘病毒属(大天 花(天花)和牛痘(牛痘))、副痘病毒属、禽痘病毒属、山羊痘病毒属、兔痘病毒属、 猪痘病毒属和昆虫痘病毒亚科。嗜肝DNA病毒科包括乙肝病毒。可作为抗原的合适来源的一种未归类病毒是肝炎δ病毒、戊肝病毒和朊病毒。另一种作为抗原来源 的病毒是Nipan病毒。其他的病毒来源包括鸟感染性粘液囊病病毒和猪呼吸和生殖 综合征病毒。甲型病毒科包括马动脉炎病毒和各种脑炎病毒。
本发明还包括用于免疫人或非人动物抗其他病原体的免疫原，所述病原体包 括感染人和非人脊椎动物的细菌、真菌、寄生微生物或多细胞寄生虫，或来自癌 细胞或肿瘤细胞的病原体。细菌病原体的实例包括致病性革兰氏阳性球菌，其包 括肺炎球菌、葡萄球菌(及其产生的毒素，例如：肠毒素B)和链球菌。致病性革兰 氏阴性球菌包括脑膜炎球菌、淋球菌。致病性肠革兰氏阴性杆菌包括肠杆菌科； 假单胞菌属、不动杆菌属和埃肯菌属；类鼻疽假单孢菌属；沙门氏菌属；志贺氏 菌属；嗜血杆菌属：莫拉氏菌属；杜克雷嗜血杆菌(H.ducreyi)(其导致软下疳)；布 鲁杆菌(布鲁杆菌病)；野兔热弗朗西丝菌(Franisellatularensis)(其导致兔热病)；鼠 疫耶尔森菌(鼠疫)和其他耶尔森菌属(巴斯德菌属)；念珠状链杆菌和螺菌属；革兰 氏阳性杆菌，其包括单核细胞增多李斯特菌；红斑丹毒丝菌；白喉棒状杆菌 (Corynebacterium diphtheria)(白喉)；霍乱；炭疽杆菌(B.anthracis)(炭疽)；多诺万病 (腹股沟肉芽肿)和巴尔通体病。致病性厌氧细菌导致的疾病包括破伤风；肉毒中 毒(肉毒梭菌(Clostridum botulimum)及其毒素)；产气荚膜梭菌(Clostridiumperfringen)及其ε毒素；其他梭菌属；结核病；麻风和其他分枝杆菌属。致病性螺 旋体疾病包括梅毒；密螺旋体病：雅司病、品他病和地方性梅毒；以及钩端螺旋 体病。较高致病性细菌和致病性真菌导致的其他感染包括鼻疽(鼻疽伯克霍尔德氏 菌(Burkholderiamallei)；放线菌病；诺卡菌病；隐球菌病、芽生菌病、组织胞浆 菌病和球孢子菌病；念珠菌病、曲霉病和毛霉病；孢子丝菌病；副球孢子菌病、 石样真菌病、球拟酵母病、足分枝菌病和着色真菌病；以及皮真菌病。立克次体 感染包括斑疹伤寒热、落矶山斑疹热、Q热(伯内特科克斯立克次体(Coxiella burnetti))和立克次氏体痘。支原体和衣原体感染的实例包括：支原体肺炎、性病 性淋巴肉芽肿、鹦鹉热和围产期衣原体感染。致病性真核细胞包括致病性原生动 物和蠕虫，并且由其产生的感染包括：阿米巴病、疟疾、利什曼病、锥虫病、弓 形体病、卡氏肺囊虫(Pneumocystis carinii)、Trichans、鼠弓形体(Toxoplasma gondii)、巴贝虫病、贾第虫病、旋毛虫病、丝虫病、血吸虫病、线虫、吸虫(trematode)或 吸虫(fluke)感染和绦虫(绦虫)感染。
这些生物体和/或其产生的毒素中有许多已被疾病控制中心[(CDC)，健康与 人类服务部(Department of Heath and Human Services)，美国]认定为是可用于生物 攻击的物质。例如，某些此类生物物质包括目前分类为A类物质的炭疽杆菌(Bacillus anthracis)(炭疽)、肉毒梭菌(Clostridium botulinum)及其毒素(肉毒杆菌毒素)、鼠疫 耶尔森菌(Yersinia pestis)(鼠疫)、大天花(天花)、野兔热弗朗西丝菌(Franisella tularensis)(兔热病)和病毒性出血热[丝状病毒(例如：埃博拉病毒、马尔堡病毒)和 沙粒病毒[例如：拉沙病毒、马丘博病毒]；目前分类为B类物质的伯内特科克斯立 克次体(Coxiellaburnetti)(Q热)、布鲁杆菌(布鲁杆菌病)、鼻疽伯克霍尔德氏菌 (Burkholderia mallei)(鼻疽)、假鼻疽伯克霍尔德氏菌(Burkholderia pseudomallei)(类 鼻疽)、蓖麻(Ricinuscommunis)及其毒素(蓖麻蛋白毒素)、产气荚膜梭菌(Clostridium perfringen)及其毒素(ε毒素)、葡萄球菌(Staphylococcus)及其毒素(肠毒素B)、鹦鹉 热衣原体(Chlamydiapsittaci)(鹦鹉热)、水上安全威胁(water safety threat)(例如：霍 乱弧菌(Vibriocholerae)、小隐孢子虫(Cryptosporidium parvum)、斑疹伤寒热(普氏 立克次体(Richettsia powazekii)和病毒性脑炎(甲型病毒，例如：委内瑞拉马脑炎、 东部马脑炎、西部马脑炎)；以及目前分类为C类物质的Nipan病毒和汉坦病毒。此 外，其他如此分类或不同分类的生物体也可能在将来可被鉴定和/或用于这种目 的。容易理解的是，本文所述的病毒载体和其他构建体可用于传递来自这些生物 体的抗原、病毒、其毒素或其他副产物，这可预防和/或治疗这些生物物质引起 的感染或其他不良反应。
施用本发明的载体来递送抗T细胞可变区的免疫原引发包括CTL在内的免疫应 答来消除T细胞。在类风湿性关节炎(RA)中，己鉴定了参与该疾病的数种特定TCR 可变区。这些TCR包括V-3、V-14、V-17和V-17。因此，递送编码这些多肽中至少一 种的核酸序列将引发以参与RA的T细胞为目标的免疫应答。在多发性硬化症(MS) 中，已鉴定了参与该疾病的数种特定TCR可变区。这些TCR包括V-7和V-10。因此， 递送编码这些多肽中至少一种的核酸序列将引发以参与MS的T细胞为目标的免疫 应答。在硬皮病中，已鉴定了参与该疾病的数种特定TCR可变区。这些TCR包括V-6、 V-8、V-14和V-16、V-3C、V-7、V-14、V-15、V-16、V-28和V-12。因此，递送编码这 些多肽中至少一种的核酸分子将引发以参与硬皮病的T细胞为目标的免疫应答。
因此，本发明的rAAV衍生的重组病毒载体提供了一种有效的基因转送载体， 它们能在体内或体外将选定转基因递送至选定宿主细胞中，既使该生物体具有针 对一种或多种AAV源的中和抗体。在一个实施方案中，rAAV与细胞体外混合，使 用常规方法培养被感染的细胞，并将被转导细胞回输给患者。
这些组合物尤其适用于治疗目的和免疫接种目的的基因递送，所述免疫接种 包括诱导保护性免疫。本发明的AAV和包含本发明的AAV的组合物还可以用于免疫 疗法，例如在为本申请申请人所共有的、2004年4月28日递交的“致免疫分子的连 续的腺病毒和AAV介导的传递”的美国专利申请号60/565,936。
此外，本发明的组合物也可用于体外生产所需基因产物。就体外生产而言， 可如下获得所需产物(例如：蛋白质)：用含有编码所需产物的分子的rAAV转染宿 主细胞，并在允许表达的条件下培养细胞培养物，然后从培养物中获得所需产物 。然后，可视需要纯化和分离该表达产物。合适的转染、细胞培养、纯化和分离 技术是本领域技术人员已知的。
以下实施例阐述了本发明的几个方面与实施方案。
实施例1
根据本发明的方法，将AAV序列与包含分化体A、B、C、D、E和F(由AAV9代表) 各自代表性序列的文库比对时，确定了其具有单现突变。下列表格显示了有待改 变为保守序列的衣壳序列和单现突变。为表示某些突变，单现突变后面有*，再后 面是用于取代它的氨基酸残基。为表示其他有些突变，单现突变后面是其氨基酸 位置和用来取代它的残基。
氨基酸编号是基于这些AAV衣壳各自的已公开序列。参见，例如：G.Gao等人，J.Virol.，78(12)：6381-6388(2004年6月)和国际专利公开号WO 2004/042397[其中的 全部序列存放在GenBank中]，以及2004年9月30日提交的国际专利公开号WO 2005/033321，其引用作为参考。
例如，就下表而言，各名称应如下理解。Cy5R1指氨基酸残基位点13处为天 冬氨酸(D)的经修正氨基酸序列SEQ ID NO：24；cy5天然氨基酸序列的第13位残基 处是甘氨酸。Cy5R2指氨基酸残基位点13处(在天然序列中为甘氨酸)为天冬氨酸且 在氨基酸残基位点403处(在天然序列中为天冬氨酸)为天冬酰胺的经修正氨基酸 序列SEQ ID NO：24。Cy5R3具有经修正的氨基酸序列SEQ ID NO：24，具有与Cy5R2 相同的改变，此外，在位点158处为赖氨酸(在天然序列中为天冬酰胺)，在位点161 处为谷氨酰胺(在天然序列中为脯氨酸)。鉴于以上信息，本领域技术人员可容易 地确定在下表中所列的其他单现突变改变。
Figure BDA0001170764950000311
Figure BDA0001170764950000321
实施例2
在初步研究中，选择五个克隆来试验本发明的单现突变方法。下表提供了这 5个克隆的表型描述。在预测单现突变数目之外还列明了所属分化体和血清型分类 。
当其滴度低于1×1011GC时，包装表型认定为不足；当低于1×1012GC时，认 定为低；当低于1×1013GC时，认为是好；更高则认为是优良。
通过CB.A1AT基因表达来确定基因转移表型，并且表示如下：“+++”表示比靶 组织的首选候选物更好，“++”、“+”和“-”分别表示与首选候选物(肌肉：AAV1，肝： AAV8，肺：AAV9)的A1AT血清浓度水平相比超过该水平的50％、相当于该水平的 10-50％，低于该水平的10％。“n/a”表明不能产生用于体内基因转移研究的足够水 平的载体。
单现突变校正克隆如下进行。对原包装质粒进行定点诱变。在此之后，通过 Pstl消化测定载体骨架的完整性，并通过测序确认单现突变的校正。然后在12－孔 板上一式三份产生EGFP-表达载体，与包含单现突变的亲代载体、AAV2和AAV2/8 阳性对照生产以及作为阴性对照的不存在包装质粒情况下的生产并列。在3×冷冻 之后，将等量的收获的裂解物培养于293细胞。在转导后72小时，通过流式细胞计 数法检测eGFP表达。
在克隆rh.37、rh.2、ch.5、rh.13和rh.8中进行单现突变的定位诱变。选择这些 特定的序列来代表以前文献中记载的各种表型。
Figure BDA0001170764950000322
Figure BDA0001170764950000331
在5个克隆中的4个中观察到载体表达的增加。以前显示低包装产量的rh.37和rh.2的增加最为显著。这些载体产生颗粒的生产水平可满足检测所需。载体rh.8和 rh.13显示了转导率提高。
为了区分单现突变对转导的作用与对包装和装配的作用，制备小量的载体制 剂，并通过定量PCR进行耐Dnase颗粒滴定。就rh.37可观察到载体产量的两倍对数 (two-log)增加。rh.8显示滴度的5倍增加，而rh.13表现不变。与AAV2和AAV2/8产物 相比，并且在推广到大量制备时，经单现突变校正的克隆的滴度全都在可接受的 范围内。没有对rh.2进行滴定测定。
随后在每一细胞相等颗粒数的转导环境中体外监测单现突变改变的作用。对rh.8和rh.13用293细胞进行滴定。全部感染复数(MOI)的转导效率的都适中增加。
这最初5个克隆的亚组中，3个能够转导细胞并具有生产能力。两个克隆在该 试验设定的环境中不能产生任何eGFP表达。这很可能是由于某种无法由单现突变 方法预知的载体包装缺陷所致。
使用本发明的方法来校正AAV克隆hu.46中的四个预计单现突变位点：P156SR362C S393F A676。但是，这些修正没有产生可回复其活性的AAV，这表明了在 hu.46序列中有其他类型的致死错误。
实施例3－具有改变衣壳的病毒载体的体外分析
使用本发明的方法，改变rh.64和hu.29的衣壳蛋白，然后如实施例2和G.Gao 等人，Proc Natl Acad Sci美国，99，11854-9(2002年9月3日)所述通过假型包装构建 具有改变衣壳的病毒载体。
简短地说，用表达强化绿色荧光蛋白(EGFP)的载体体外检测载体在人内皮肾 细胞(293细胞)中的转导效率。在与wtAd5一起短暂预孵育之后，在有104GC/细胞 的假型AAVCMVeGFP颗粒存在下孵育这些293细胞。通过检测灵敏度为5细胞/10K 的FACS分析测定每10,000个细胞中eGFP阳性细胞的数目。
在R697W改变之后，按本发明修正Rh.64衣壳提供了效率提高100-倍的修正 rh.64颗粒。随后的V686E突变将包装能力提高了两倍。
按本发明修正Hu.29衣壳，通过G396E这一改变提供了包装能力缺陷获得修复 的rh.64病毒颗粒。据观察，病毒生产的提高超过1000倍。
20多个修正AAV病毒颗粒中许多显示表达增强，这些病毒颗粒包括AAV6.1、hu.48R1、hu.48R2、hu.44R2、hu.44R3、rh.48.2、rh.48.2、rh.48.2.1。
实施例4－在体内基因转移应用中单现突变的效应
在体内环境设定中研究了单现突变体的效应。已开始用C57B/6小鼠对许多按 照本发明方法修正的载体进行了基因转移研究。开始了肌肉定向和肝定向的研究， 并且以目前用于特定应用的首选候选物为基准进行了比较。
选择人的α-抗胰蛋白酶(A1AT)作为载体中的敏感定量报告基因，并使其在 CMV-增强鸡β-肌动蛋白启动子控制下表达。使用CB启动子能够实现高水平的非组 织特异性和组成性的A1AT基因转移，并容许在任何感兴趣组织中使用相同的载体 制剂来研究基因转移。
选择肌肉作为第一个靶组织。将40种不同的新载体(基于各含相应单现突变体 的24个不同克隆)肌内注射到C57B/6小鼠的后肢中。用CB.A1AT转基因盒，以1× 1011GC/动物来进行全部试验。每一分化体的每组每鼠每次使用等量的载体(50μl) 。每个独立研究包括一个或两个分化体和对照组，所述对照组包括分化体的代表 性血清型，AAV2/8和AAV2/1，以它们为基准来研究定向于肌肉的基因转移。在注 射之后的第7、14、28和63天检测转基因的表达，并用特异性的hA1AT ELISA来评 定。
获得了几种分离株和单现突变校正在门内(intraportal)肝定向注射之后的性能数据。初步结果表明大部分校正克隆的表现与原分离株相当或更好。
就一种特定的克隆即cy.5而言，单现突变校正看来对肌肉转导具有有益的作 用。携带4个单现突变校正的克隆cy.5R4，与原始分离株已有的适当的肌肉趋性相 比，基因转移的效率进一步提高。cy.5R4的表现等同于或稍好于作为基准对照的 AAV2/1和AAV2/7。
以前应过低滴度而无法进一步测评的分离株rh.64，在对一个单现突变进行校 正之后在肌肉中表现特别好。Rh.64R1表现好于rh.64.2，其产生的hA1AT水平高于 其最近的相关血清型AAV2/8，并且高于AAV2/7。
在其他的研究中，给小鼠注射基于分化体分组的载体。用表达CB.hA1AT的载 体按照1×1011GC/小鼠给药。用特异性的hA1AT ELISA测定hA1AT的血清浓度水平。
单现突变在体内对基因转移的作用看来取决于分离株和靶组织。有数项观测 结果是有意义的。
就某些单现突变克隆而言，定性地说，单现突变的作用在肌肉中和在肝中类 似(例如：rh.2、rh.13或cy.5)。分离株hu.48和rh.48显示，在肌肉中，随着回复的单 现突变数目的增加，表达也增加。
其他克隆，如rh.64和aav6，显示了特定的表达特征。以分离株hu.48R2为例， 其包装效率比hu.48R3大约低10倍它的，但后者转导肌肉的效率大约低5倍。AAV6 包含两个单现突变。它们对于包装都具有中等强度的作用，它们的组合使AAV6包 装达到了基准水平。体外，亲代克隆和各不同克隆之间差别小得几乎难以察觉。 体内，在肌肉中，AAV6.1和AAV6.1.2减弱基因转移，而AAV6.2则中等强度地增强 转移。
实施例5－在肺和肝中单现突变－校正的AAV的评定
在肺和肝中进一步评定了就包装和基因转移效率通过单现突变残基回复突 变而优化的AAV载体。给出了不含单现突变载体和单现突变残基被回复为保守氨 基酸的载体的数据。
A.气管内注射之后，pi2、rh32.33、AAV2/9、AAV2/5、rh.2R、ch5R介导的CB.A1ATAAV基因的肺转移鉴定
比较了数种AAV衣壳进入目标即肺的能力。测定了血清中CB.A1AT的水平。接 受评定的AAV无单现突变(pi2、rh32.33、AAV2/9、AAV2/5、rh.2R、ch5R)或包含一 个单现突变(rh.2、rh.8)。AAV2/5和AAV2/9被作为基准。
使用携带有包含在上述衣壳中的CB.A1AT表达盒(即：AAV2 5'ITR、鸡β-肌动蛋 白启动子(CB)、人α1-抗胰蛋白酶(A1AT)、AAV2 3'ITR)或CB.nLacZ表达盒(即：AAV2 5'ITR、核定位β-半乳糖苷酶(nLacZ)、AAV2 3'ITR)的载体在C57B/6小鼠(雄性、每组5 只)中进行基因转移研究。简短地说，将50μL的单现突变－校正的或无单现突变的 载体与携带A1AT的载体和携带nLacZ(1x1011GC)的载体进行气管内共灌输(1×1011基因组拷贝(GC))。
在第12天和第20天，采集了20份血液，并测定了A1AT的血清浓度水平 (ngAAT/mL血清)。数据显示：在1×1011GC气管内(IT)注射之后，rh.2到rh.2R在肺中 使人αl-抗胰蛋白酶的表达显著增加。另外，还鉴定了一批无单现突变残基的AAV 载体。全部载体显示了在肺中可接受的表达水平。
B.与AAV2/5和AAV2/9相比，AAV6单现突变载体的评定
评定单现突变校正克隆AAV6。使用本发明的单现突变校正法和本文所描述的 假型包装技术来制备修正AAV6(AAV6.2)。如实施例5所述制备携带A1AT和LacZ表达 盒的AAV6.2颗粒，同时鼻内(1×1011GC)和气管内感染。用ELISA评定血清和支气管 肺泡液(BAL)中的AAT表达。根据总蛋白的表达水平进行归一。用ELISA检测肺组织 匀浆中的β-半乳糖苷酶来测定LacZ表达。在第21天进行尸检。
在采用C57Bl/6小鼠(雄性，n＝8/组)的研究中将这些载体与AAV2/6、AAV2/5和AAV2/9相比较，所述AAV2/6是目前肺基因转移的临床候选载体。
在血清A1AT分泌方面，AAV6.2与AAV6相比存在统计上的显著改善。AAV6.2与 其他载体(包括AAV2/9和AAV2/5)相比，还显示了较高的A1AT水平。在BAL中，略有 改善，肺组织匀浆中的LacZ表达亦是如此。然而，由于动物与动物间差异巨大， 所以从LacZ定量中得不出结论。
当测定AAV基因表达的定位时，与AAV2/6相比，观察到在AAV2/6.2组中，核定 位LacZ着色较深。在囊肿性纤维化等疾病的主要目标肺气管上皮中，观察到了与 AAV2/6和AAV2/5相比明显的改进。
C.用分化体B和分化体C的AAV成员在C57B1/6小鼠中进行 AAV.CB.A1AT(1x1011GC)的静脉内(iv)注射
所用的全部载体都不含来自分离物(AAV2/8、AAV2、hu.13、hu.51、hu.11、hu.53)或通过突变(hu.29R)形成的单现突变残基。将全部载体与作为基准的AAV2/8(分化 体E)相比较。
D.分化体E的AVV成员静脉注射。成员rh.64Rl、rh.64R2、rh.2R的是单现突变优 化的。其他载体都是无单现突变的。
发现，AAV分化体B和C的成员，包括单现突变优化克隆hu.29R，它们的表达 彼此近似至相当。hu.29R由hu.29重构而成，回复了其包装能力，现在，其表现出 与该病毒家族其他成员近似的基因转移功能。
就接受测定的分化体E载体而言，不论是天然无单现突变载体还是经单现突 变校正的载体，表现都与目前肝定向基因转移的最佳载体AAV2/8近似。尤其值得 注意的是AAVrh64Rl和rh.64R2。rh.64曾被认为有包装缺陷，但现在，在一个(rh.64Rl) 或两个(rh.64R2)单现突变转变之后，其肝定向基因转移同样良好。就rh.2而言，对 单现突变校正相对应的是基因运送效率超过10倍的显著提高。
本说明书中引用的所有出版物，包括专利都在此处引用作为参考。尽管参考 特别优选的实施方式描述了本发明，但应该理解的是可作出改进而不脱离本发明 的精神。
序列表
<110> 宾夕法尼亚州立大学托管会
<120> 增强腺相关病毒载体功能的方法
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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 Ser 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 Glu Phe Ser 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 Ser Thr Gly Gly Thr Gln Gly Thr Gln Gln Leu Leu
450 455 460
Phe Ser Gln Ala Gly Pro Ala Asn Met Ser Ala Gln Ala Lys Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met
530 535 540
Phe Gly Lys Gln Gly Ala Gly Arg Asp Asn Val Asp Tyr Ser Ser 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 Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Thr Asn Thr Gly
580 585 590
Pro Ile Val Gly Asn 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 Ser Gln Ala Lys Leu Ala 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 Asn Val Asp Phe Ala Val Asn Thr Glu
705 710 715 720
Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg
725 730 735
Asn Leu
<210> 4
<211> 738
<212> PRT
<213> 猕猴腺相关病毒克隆 46衣壳蛋白
<400> 4
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 Ile Gly Glu Pro
180 185 190
Pro Ala Ala Pro Ser Ser Val Gly Ser Gly 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 Ser 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 Ser Phe Ser 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 Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu
450 455 460
Phe Ser Gln Ala Gly Pro Ser Asn Met Ser Ala Gln Ala Arg Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
Asn Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Ile Leu Met
530 535 540
Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Asn Val
545 550 555 560
Met Leu Thr Ser Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr
565 570 575
Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala
580 585 590
Pro Ile Val Gly Ala 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 Ala Phe Asn Gln Ala 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 Asn 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> 5
<211> 738
<212> PRT
<213> 猕猴腺相关病毒克隆 73 衣壳
<400> 5
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 Ala Pro Ser Ser Val Gly Ser Gly 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 Ser 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 Ser Phe Ser 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 Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu
450 455 460
Phe Ser Gln Ala Gly Pro Ser Asn Met Ser Ala Gln Ala Arg Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
Asn Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Ile Leu Met
530 535 540
Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Asn 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 Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Arg Gln Asn Thr Ala
580 585 590
Pro Ile Val Gly Ala 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 Ala Phe Asn Gln Ala 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 Asn 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> 6
<211> 736
<212> PRT
<213> 猕猴腺相关病毒克隆 74 衣壳
<400> 6
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 Leu Asn Leu Lys Pro Gly Ala Pro Gln Pro
20 25 30
Lys Ala Asn Gln Gln Lys Gln Asp Asn Ala Arg Gly Leu Val Leu Pro
35 40 45
Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Asp Pro
50 55 60
Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Gly
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 Gln Lys Asp Thr Ser Phe Gly Gly
100 105 110
Asn Leu Gly Lys Ala Val Phe Gln Ala Lys Lys Arg Ile Leu Glu Pro
115 120 125
Leu Gly Leu Val Glu Thr Pro Ala Lys Thr Ala Pro Gly Lys Lys Arg
130 135 140
Pro Val Asp Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Ser Gly Ile
145 150 155 160
Gly Lys Lys Ser Pro His Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln
165 170 175
Thr Gly Glu Ala Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro
180 185 190
Pro Ser Asp Pro Ser Ser Val Gly Ser Gly Thr Met Ala Ala Gly Gly
195 200 205
Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn
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 Ser Gln Ser Gly Ala Thr 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 Ser Phe Lys Leu Phe Asn Ile Gln
305 310 315 320
Val Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn
325 330 335
Leu Thr Ser Thr Val Gln Val Phe Thr 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 Gln 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 Gln Gly Thr Asn Ala Thr Val Gln Gly Ala Lys Leu Gln Phe Ser
450 455 460
Gln Ala Gly Pro Ser Asn Met Arg Asp Gln Ala Arg Asn Trp Leu Pro
465 470 475 480
Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ala Asn Asp Asn
485 490 495
Asn Asn Ser Glu Tyr Ala Trp Thr Gly Ala Thr Lys Tyr His Leu Asn
500 505 510
Gly Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys
515 520 525
Asp Asp Glu Glu Lys Phe Phe Pro Met Asn Gly Thr Leu Val Phe Gly
530 535 540
Lys Asn Gly Ala Gly Asn Ser Asn Val Asp Ile Glu Asn Val Met Ile
545 550 555 560
Thr Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln
565 570 575
Tyr Gly Val Val Ser Asp Asn Leu Gln Ser Ser Asn Thr Arg Pro Ile
580 585 590
Thr Gly Asp Val Asp Ser Gln Gly Val 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 Ala Thr Thr Phe Thr Pro Gly Lys Phe Ala Ser Phe Ile Thr
660 665 670
Gln Tyr Ser Thr Gly Gln Val Ser Val Gln 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 Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn 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> 7
<211> 2208
<212> DNA
<213> 腺相关病毒 血清型2
<400> 7
atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaataaga 60
cagtggtgga agctcaaacc tggcccacca ccaccaaagc ccgcagagcg gcataaggac 120
gacagcaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac 180
aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa agcctacgac 240
cggcagctcg acagcggaga caacccgtac ctcaagtaca accacgccga cgcggagttt 300
caggagcgcc ttaaagaaga tacgtctttt gggggcaacc tcggacgagc agtcttccag 360
gcgaaaaaga gggttcttga acctctgggc ctggttgagg aacctgttaa gacggctccg 420
ggaaaaaaga ggccggtaga gcactctcct gtggagccag actcctcctc gggaaccgga 480
aaggcgggcc agcagcctgc aagaaaaaga ttgaattttg gtcagactgg agacgcagac 540
tcagtacctg acccccagcc tctcggacag ccaccagcag ccccctctgg tctgggaact 600
aatacgatgg ctacaggcag tggcgcacca atggcagaca ataacgaggg cgccgacgga 660
gtgggtaatt cctcgggaaa ttggcattgc gattccacat ggatgggcga cagagtcatc 720
accaccagca cccgaacctg ggccctgccc acctacaaca accacctcta caaacaaatt 780
tccagccaat caggagcctc gaacgacaat cactactttg gctacagcac cccttggggg 840
tattttgact tcaacagatt ccactgccac ttttcaccac gtgactggca aagactcatc 900
aacaacaact ggggattccg acccaagaga ctcaacttca agctctttaa cattcaagtc 960
aaagaggtca cgcagaatga cggtacgacg acgattgcca ataaccttac cagcacggtt 1020
caggtgttta ctgactcgga gtaccagctc ccgtacgtcc tcggctcggc gcatcaagga 1080
tgcctcccgc cgttcccagc agacgtcttc atggtgccac agtatggata cctcaccctg 1140
aacaacggga gtcaggcagt aggacgctct tcattttact gcctggagta ctttccttct 1200
cagatgctgc gtaccggaaa caactttacc ttcagctaca cttttgagga cgttcctttc 1260
cacagcagct acgctcacag ccagagtctg gaccgtctca tgaatcctct catcgaccag 1320
tacctgtatt acttgagcag aacaaacact ccaagtggaa ccaccacgca gtcaaggctt 1380
cagttttctc aggccggagc gagtgacatt cgggaccagt ctaggaactg gcttcctgga 1440
ccctgttacc gccagcagcg agtatcaaag acatctgcgg ataacaacaa cagtgaatac 1500
tcgtggactg gagctaccaa gtaccacctc aatggcagag actctctggt gaatccgggc 1560
ccggccatgg caagccacaa ggacgatgaa gaaaagtttt ttcctcagag cggggttctc 1620
atctttggga agcaaggctc agagaaaaca aatgtggaca ttgaaaaggt catgattaca 1680
gacgaagagg aaatcaggac aaccaatccc gtggctacgg agcagtatgg ttctgtatct 1740
accaacctcc agagaggcaa cagacaagca gctaccgcag atgtcaacac acaaggcgtt 1800
cttccaggca tggtctggca ggacagagat gtgtaccttc aggggcccat ctgggcaaag 1860
attccacaca cggacggaca ttttcacccc tctcccctca tgggtggatt cggacttaaa 1920
caccctcctc cacagattct catcaagaac accccggtac ctgcgaatcc ttcgaccacc 1980
ttcagtgcgg caaagtttgc ttccttcatc acacagtact ccacgggaca ggtcagcgtg 2040
gagatcgagt gggagctgca gaaggaaaac agcaaacgct ggaatcccga aattcagtac 2100
acttccaact acaacaagtc tgttaatgtg gactttactg tggacactaa tggcgtgtat 2160
tcagagcctc gccccattgg caccagatac ctgactcgta atctgtaa 2208
<210> 8
<211> 2187
<212> DNA
<213> cy.5 核酸
<400> 8
atggctgccg atggttatct tccagattgg ctcgagggca acctctctga gggcattcgc 60
gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120
gacggccggg gtctggtgct tcctggctac aggtacctcg gacccttcaa cggactcgac 180
aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 240
aagcagctcg agcaggggga caacccgtac ctcaagtaca accacgccga cgccgagttt 300
caggagcgtc ttcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360
gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420
ggaaagaaga gacccataga atcccccgac tcctccacgg gcatcggcaa gaacggccag 480
ccgcccgcta aaaagaagct caactttggg cagactggcg actcagagtc agtgcccgac 540
ccccaacctc tcggagaacc tcccgccgcg ccctcaggtc tgggatctgg tacaatggct 600
gcaggcggtg gcgcaccaat ggcagacaat aacgaaggcg ccgacggagt gggtaatgcc 660
tccggaaatt ggcattgcga ttccacatgg ctgggcgaca gagtcatcac caccagcacc 720
cgcacctggg ccctgcccac ctacaacaac cacctctaca agcagatatc aagtcagagc 780
ggggctacca acgacaacca cttcttcggc tacagcaccc cctggggcta ttttgacttc 840
aacagattcc actgccactt ctcaccacgt gactggcagc gactcatcaa caacaactgg 900
ggattccggc ccagaaagct gcggttcaag ttgttcaaca tccaggtcaa ggaggtcacg 960
acgaacgacg gcgttacgac catcgctaat aaccttacca gcacgattca ggtcttctcg 1020
gactcggagt accaactgcc gtacgtcctc ggctctgcgc accagggctg cctccctccg 1080
ttccctgcgg acgtgttcat gattcctcag tacggatatc tgactctaaa caacggcagt 1140
cagtctgtgg gacgttcctc cttctactgc ctggagtact ttccttctca gatgctgaga 1200
acgggcgata actttgaatt cagctacacc tttgaggaag tgcctttcca cagcagctat 1260
gcgcacagcc agagcctgga ccggctgatg aatcccctca tcgaccagta cctgtactac 1320
ctggcccgga cccagagcac tacggggtcc acaagggagc tgcagttcca tcaggctggg 1380
cccaacacca tggccgagca atcaaagaac tggctgcccg gaccctgtta tcggcagcag 1440
agactgtcaa aaaacataga cagcaacaac aacagtaact ttgcctggac cggggccact 1500
aaataccatc tgaatggtag aaattcatta accaacccgg gcgtagccat ggccaccaac 1560
aaggacgacg aggaccagtt ctttcccatc aacggagtgc tggtttttgg caaaacgggg 1620
gctgccaaca agacaacgct ggaaaacgtg ctaatgacca gcgaggagga gatcaaaacc 1680
accaatcccg tggctacaga agaatacggt gtggtctcca gcaacctgca atcgtctacg 1740
gccggacccc agacacagac tgtcaacagc cagggggctc tgcccggcat ggtctggcag 1800
aaccgggacg tgtacctgca gggtcccatc tgggccaaaa ttcctcacac ggacggcaac 1860
tttcacccgt ctcccctgat gggcggattt ggactcaaac acccgcctcc tcaaattctc 1920
atcaaaaaca ccccggtacc tgctaatcct ccagaggtgt ttactcctgc caagtttgcc 1980
tcatttatca cgcagtacag caccggccag gtcagcgtgg agatcgagtg ggaactgcag 2040
aaagaaaaca gcaaacgctg gaatccagag attcagtaca cctcaaatta tgccaagtct 2100
aataatgtgg aatttgctgt caacaacgaa ggggtttata ctgagcctcg ccccattggc 2160
acccgttacc tcacccgtaa cctgtaa 2187
<210> 9
<211> 2217
<212> DNA
<213> 猕猴腺相关病毒, rh.10
<400> 9
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 tggctgcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 660
ggagtgggta gttcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720
atcaccacca gcacccgaac ctgggccctc cccacctaca acaaccacct ctacaagcaa 780
atctccaacg ggacttcggg aggaagcacc aacgacaaca cctacttcgg ctacagcacc 840
ccctgggggt attttgactt taacagattc cactgccact tctcaccacg tgactggcag 900
cgactcatca acaacaactg gggattccgg cccaagagac tcaacttcaa gctcttcaac 960
atccaggtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taaccttacc 1020
agcacgattc aggtctttac ggactcggaa taccagctcc cgtacgtcct cggctctgcg 1080
caccagggct gcctgcctcc gttcccggcg gacgtcttca tgattcctca gtacgggtac 1140
ctgactctga acaatggcag tcaggccgtg ggccgttcct ccttctactg cctggagtac 1200
tttccttctc aaatgctgag aacgggcaac aactttgagt tcagctacca gtttgaggac 1260
gtgccttttc acagcagcta cgcgcacagc caaagcctgg accggctgat gaaccccctc 1320
atcgaccagt acctgtacta cctgtctcgg actcagtcca cgggaggtac cgcaggaact 1380
cagcagttgc tattttctca ggccgggcct aataacatgt cggctcaggc caaaaactgg 1440
ctacccgggc cctgctaccg gcagcaacgc gtctccacga cactgtcgca aaataacaac 1500
agcaactttg cctggaccgg tgccaccaag tatcatctga atggcagaga ctctctggta 1560
aatcccggtg tcgctatggc aacccacaag gacgacgaag agcgattttt tccgtccagc 1620
ggagtcttaa tgtttgggaa acagggagct ggaaaagaca acgtggacta tagcagcgtt 1680
atgctaacca gtgaggaaga aattaaaacc accaacccag tggccacaga acagtacggc 1740
gtggtggccg ataacctgca acagcaaaac gccgctccta ttgtaggggc cgtcaacagt 1800
caaggagcct tacctggcat ggtctggcag aaccgggacg tgtacctgca gggtcctatc 1860
tgggccaaga ttcctcacac ggacggaaac tttcatccct cgccgctgat gggaggcttt 1920
ggactgaaac acccgcctcc tcagatcctg attaagaata cacctgttcc cgcggatcct 1980
ccaactacct tcagtcaagc taagctggcg tcgttcatca cgcagtacag caccggacag 2040
gtcagcgtgg aaattgaatg ggagctgcag aaagaaaaca gcaaacgctg gaacccagag 2100
attcaataca cttccaacta ctacaaatct acaaatgtgg actttgctgt taacacagat 2160
ggcacttatt ctgagcctcg ccccatcggc acccgttacc tcacccgtaa tctgtaa 2217
<210> 10
<211> 2187
<212> DNA
<213> 猕猴腺相关病毒, rh.13
<400> 10
atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60
gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120
gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180
aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 240
aagcagctcg agcaggggga caacccgtac ctcaagtaca accacgccga cgccgagttt 300
caggagcgtc ttcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360
gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420
ggaaagaaga gacccataga atcccccgac tcctccacgg gcatcggcaa gaaaggccag 480
cagcccgcta aaaagaagct caactttggg cagactggcg actcagagtc agtgcccgac 540
ccccaacctc tcggagaacc tcccgccgcg ccctcaggtc tgggatctgg tacaatggct 600
gcaggcggtg gcgcaccaat ggcagacaat aacgaaggcg ccgacggagt gggtaatgcc 660
tccggaaatt ggcattgcga ttccacatgg ctgggcgaca gagtcatcac caccagcacc 720
cgcacctggg ccctgcccac ctacaacaac cacctctaca agcagatatc aagtcagagc 780
ggggctacca acgacaacca cttcttcggc tacagcaccc cctggggcta ttttgacttc 840
aacagattcc actgccactt ctcaccacgt gactggcagc gactcatcaa caacaactgg 900
ggattccggc ccagaaagct gcggttcaag ttgttcaaca tccaggtcaa ggaggtcacg 960
acgaacgacg gcgttacgac catcgctaat aaccttacca gcacgattca ggtcttctcg 1020
gactcggagt accaactgcc gtacgtcctc ggctctgcgc accagggctg cctccctccg 1080
ttccctgcgg acgtgttcat gattcctcag tacggatatc tgactctaaa caacggcagt 1140
cagtctgtgg gacgttcctc cttctactgc ctggagtact ttccttctca gatgctgaga 1200
acgggcaata actttgaatt cagctacacc tttgaggaag tgcctttcca cagcagctat 1260
gcgcacagcc agagcctgga ccggctgatg aatcccctca tcgaccagta cctgtactac 1320
ctggcccgga cccagagcac tacggggtcc acaagggagc tgcagttcca tcaggctggg 1380
cccaacacca tggccgagca atcaaagaac tggctgcccg gaccctgtta tcggcagcag 1440
agactgtcaa aaaacataga cagcaacaac aacagtaact ttgcctggac cggggccact 1500
aaataccatc tgaatggtag aaattcatta accaacccgg gcgtagccat ggccaccaac 1560
aaggacgacg aggaccagtt ctttcccatc aacggagtgc tggtttttgg cgaaacgggg 1620
gctgccaaca agacaacgct ggaaaacgtg ctaatgacca gcgaggagga gatcaaaacc 1680
accaatcccg tggctacaga agaatacggt gtggtctcca gcaacctgca atcgtctacg 1740
gccggacccc agacacagac tgtcaacagc cagggggctc tgcccggcat ggtctggcag 1800
aaccgggacg tgtacctgca gggtcccatc tgggccaaaa ttcctcacac ggacggcaac 1860
tttcacccgt ctcccctgat gggcggattt ggactcaaac acccgcctcc tcaaattctc 1920
atcaaaaaca ccccggtacc tgctaatcct ccagaggtgt ttactcctgc caagtttgcc 1980
tcatttatca cgcagtacag caccggccag gtcagcgtgg agatcgagtg ggaactgcag 2040
aaagaaaaca gcaaacgctg gaatccagag attcagtaca cctcaaatta tgccaagtct 2100
aataatgtgg aatttgctgt caacaacgaa ggggtttata ctgagcctcg ccccattggc 2160
acccgttacc tcacccgtaa cctgtaa 2187
<210> 11
<211> 2211
<212> DNA
<213> 腺相关病毒 血清型1
<400> 11
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 gcagtcgcca caagagccag actcctcctc gggcatcggc 480
aagacaggcc agcagcccgc taaaaagaga ctcaattttg gtcagactgg cgactcagag 540
tcagtccccg atccacaacc tctcggagaa cctccagcaa cccccgctgc tgtgggacct 600
actacaatgg cttcaggcgg tggcgcacca atggcagaca 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 atttcaacag attccactgc cacttttcac cacgtgactg gcagcgactc 900
atcaacaaca attggggatt ccggcccaag agactcaact tcaaactctt caacatccaa 960
gtcaaggagg tcacgacgaa tgatggcgtc acaaccatcg ctaataacct taccagcacg 1020
gttcaagtct tctcggactc ggagtaccag cttccgtacg tcctcggctc tgcgcaccag 1080
ggctgcctcc ctccgttccc ggcggacgtg ttcatgattc cgcaatacgg ctacctgacg 1140
ctcaacaatg gcagccaagc cgtgggacgt tcatcctttt actgcctgga atatttccct 1200
tctcagatgc tgagaacggg caacaacttt accttcagct acacctttga ggaagtgcct 1260
ttccacagca gctacgcgca cagccagagc ctggaccggc tgatgaatcc tctcatcgac 1320
caatacctgt attacctgaa cagaactcaa aatcagtccg gaagtgccca aaacaaggac 1380
ttgctgttta gccgtgggtc tccagctggc atgtctgttc agcccaaaaa ctggctacct 1440
ggaccctgtt atcggcagca gcgcgtttct aaaacaaaaa cagacaacaa caacagcaat 1500
tttacctgga ctggtgcttc aaaatataac ctcaatgggc gtgaatccat catcaaccct 1560
ggcactgcta tggcctcaca caaagacgac gaagacaagt tctttcccat gagcggtgtc 1620
atgatttttg gaaaagagag cgccggagct tcaaacactg cattggacaa tgtcatgatt 1680
acagacgaag aggaaattaa agccactaac cctgtggcca ccgaaagatt tgggaccgtg 1740
gcagtcaatt tccagagcag cagcacagac cctgcgaccg gagatgtgca tgctatggga 1800
gcattacctg gcatggtgtg gcaagataga gacgtgtacc tgcagggtcc catttgggcc 1860
aaaattcctc acacagatgg acactttcac ccgtctcctc ttatgggcgg ctttggactc 1920
aagaacccgc ctcctcagat cctcatcaaa aacacgcctg ttcctgcgaa tcctccggcg 1980
gagttttcag ctacaaagtt tgcttcattc atcacccaat actccacagg acaagtgagt 2040
gtggaaattg aatgggagct gcagaaagaa aacagcaagc gctggaatcc cgaagtgcag 2100
tacacatcca attatgcaaa atctgccaac gttgatttta ctgtggacaa caatggactt 2160
tatactgagc ctcgccccat tggcacccgt taccttaccc gtcccctgta a 2211
<210> 12
<211> 2211
<212> DNA
<213> 腺相关病毒 血清型3
<400> 12
atggctgctg acggttatct tccagattgg ctcgaggaca acctttctga aggcattcgt 60
gagtggtggg ctctgaaacc tggagtccct caacccaaag cgaaccaaca acaccaggac 120
aaccgtcggg gtcttgtgct tccgggttac aaatacctcg gacccggtaa cggactcgac 180
aaaggagagc cggtcaacga ggcggacgcg gcagccctcg aacacgacaa agcttacgac 240
cagcagctca aggccggtga caacccgtac ctcaagtaca accacgccga cgccgagttt 300
caggagcgtc ttcaagaaga tacgtctttt gggggcaacc ttggcagagc agtcttccag 360
gccaaaaaga ggatccttga gcctcttggt ctggttgagg aagcagctaa aacggctcct 420
ggaaagaagg gggctgtaga tcagtctcct caggaaccgg actcatcatc tggtgttggc 480
aaatcgggca aacagcctgc cagaaaaaga ctaaatttcg gtcagactgg agactcagag 540
tcagtcccag accctcaacc tctcggagaa ccaccagcag cccccacaag tttgggatct 600
aatacaatgg cttcaggcgg tggcgcacca atggcagaca ataacgaggg tgccgatgga 660
gtgggtaatt cctcaggaaa ttggcattgc gattcccaat ggctgggcga cagagtcatc 720
accaccagca ccagaacctg ggccctgccc acttacaaca accatctcta caagcaaatc 780
tccagccaat caggagcttc aaacgacaac cactactttg gctacagcac cccttggggg 840
tattttgact ttaacagatt ccactgccac ttctcaccac gtgactggca gcgactcatt 900
aacaacaact ggggattccg gcccaagaaa ctcagcttca agctcttcaa catccaagtt 960
agaggggtca cgcagaacga tggcacgacg actattgcca ataaccttac cagcacggtt 1020
caagtgttta cggactcgga gtatcagctc ccgtacgtgc tcgggtcggc gcaccaaggc 1080
tgtctcccgc cgtttccagc ggacgtcttc atggtccctc agtatggata cctcaccctg 1140
aacaacggaa gtcaagcggt gggacgctca tccttttact gcctggagta cttcccttcg 1200
cagatgctaa ggactggaaa taacttccaa ttcagctata ccttcgagga tgtacctttt 1260
cacagcagct acgctcacag ccagagtttg gatcgcttga tgaatcctct tattgatcag 1320
tatctgtact acctgaacag aacgcaagga acaacctctg gaacaaccaa ccaatcacgg 1380
ctgcttttta gccaggctgg gcctcagtct atgtctttgc aggccagaaa ttggctacct 1440
gggccctgct accggcaaca gagactttca aagactgcta acgacaacaa caacagtaac 1500
tttccttgga cagcggccag caaatatcat ctcaatggcc gcgactcgct ggtgaatcca 1560
ggaccagcta tggccagtca caaggacgat gaagaaaaat ttttccctat gcacggcaat 1620
ctaatatttg gcaaagaagg gacaacggca agtaacgcag aattagataa tgtaatgatt 1680
acggatgaag aagagattcg taccaccaat cctgtggcaa cagagcagta tggaactgtg 1740
gcaaataact tgcagagctc aaatacagct cccacgactg gaactgtcaa tcatcagggg 1800
gccttacctg gcatggtgtg gcaagatcgt gacgtgtacc ttcaaggacc tatctgggca 1860
aagattcctc acacggatgg acactttcat ccttctcctc tgatgggagg ctttggactg 1920
aaacatccgc ctcctcaaat catgatcaaa aatactccgg taccggcaaa tcctccgacg 1980
actttcagcc cggccaagtt tgcttcattt atcactcagt actccactgg acaggtcagc 2040
gtggaaattg agtgggagct acagaaagaa aacagcaaac gttggaatcc agagattcag 2100
tacacttcca actacaacaa gtctgttaat gtggacttta ctgtagacac taatggtgtt 2160
tatagtgaac ctcgccctat tggaacccgg tatctcacac gaaacttgtg a 2211
<210> 13
<211> 2208
<212> DNA
<213> 腺相关病毒 血清型6
<400> 13
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 gtcccctg 2208
<210> 14
<211> 2214
<212> DNA
<213> 腺相关病毒 血清型7
<400> 14
atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60
gagtggtggg acctgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120
aacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180
aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240
cagcagctca aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300
caggagcgtc tgcaagaaga tacgtcattt gggggcaacc tcgggcgagc agtcttccag 360
gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420
gcaaagaaga gaccggtaga gccgtcacct cagcgttccc ccgactcctc cacgggcatc 480
ggcaagaaag gccagcagcc cgccagaaag agactcaatt tcggtcagac tggcgactca 540
gagtcagtcc ccgaccctca acctctcgga gaacctccag cagcgccctc tagtgtggga 600
tctggtacag tggctgcagg cggtggcgca ccaatggcag acaataacga aggtgccgac 660
ggagtgggta atgcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720
attaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780
atctccagtg aaactgcagg tagtaccaac gacaacacct acttcggcta cagcaccccc 840
tgggggtatt ttgactttaa cagattccac tgccacttct caccacgtga ctggcagcga 900
ctcatcaaca acaactgggg attccggccc aagaagctgc ggttcaagct cttcaacatc 960
caggtcaagg aggtcacgac gaatgacggc gttacgacca tcgctaataa ccttaccagc 1020
acgattcagg tattctcgga ctcggaatac cagctgccgt acgtcctcgg ctctgcgcac 1080
cagggctgcc tgcctccgtt cccggcggac gtcttcatga ttcctcagta cggctacctg 1140
actctcaaca atggcagtca gtctgtggga cgttcctcct tctactgcct ggagtacttc 1200
ccctctcaga tgctgagaac gggcaacaac tttgagttca gctacagctt cgaggacgtg 1260
cctttccaca gcagctacgc acacagccag agcctggacc ggctgatgaa tcccctcatc 1320
gaccagtact tgtactacct ggccagaaca cagagtaacc caggaggcac agctggcaat 1380
cgggaactgc agttttacca gggcgggcct tcaactatgg ccgaacaagc caagaattgg 1440
ttacctggac cttgcttccg gcaacaaaga gtctccaaaa cgctggatca aaacaacaac 1500
agcaactttg cttggactgg tgccaccaaa tatcacctga acggcagaaa ctcgttggtt 1560
aatcccggcg tcgccatggc aactcacaag gacgacgagg accgcttttt cccatccagc 1620
ggagtcctga tttttggaaa aactggagca actaacaaaa ctacattgga aaatgtgtta 1680
atgacaaatg aagaagaaat tcgtcctact aatcctgtag ccacggaaga atacgggata 1740
gtcagcagca acttacaagc ggctaatact gcagcccaga cacaagttgt caacaaccag 1800
ggagccttac ctggcatggt ctggcagaac cgggacgtgt acctgcaggg tcccatctgg 1860
gccaagattc ctcacacgga tggcaacttt cacccgtctc ctttgatggg cggctttgga 1920
cttaaacatc cgcctcctca gatcctgatc aagaacactc ccgttcccgc taatcctccg 1980
gaggtgttta ctcctgccaa gtttgcttcg ttcatcacac agtacagcac cggacaagtc 2040
agcgtggaaa tcgagtggga gctgcagaag gaaaacagca agcgctggaa cccggagatt 2100
cagtacacct ccaactttga aaagcagact ggtgtggact ttgccgttga cagccagggt 2160
gtttactctg agcctcgccc tattggcact cgttacctca cccgtaatct gtaa 2214
<210> 15
<211> 2217
<212> DNA
<213> 腺相关病毒 血清型8
<400> 15
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> 16
<211> 2208
<212> DNA
<213> 腺相关病毒, hu.13
<400> 16
atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaataaga 60
cagtggtgga agctcaaacc tggcccacca ccaccaaagc ccgcagagcg gcataaggac 120
gacagcaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac 180
aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 240
cggcagctcg acagcggaga caacccgtac ctcaagtaca accacgccga cgcggagttt 300
caggagcgcc ttaaagaaga tacgtctttt gggggcaacc tcggacgagc agtcttccag 360
gcaaaaaaga gggttcttga acctctgggc ctggttgagg agcctgttaa aacggctccg 420
ggaaaaaaga ggccggtaga gcactctcct gcggagccag actcctcctc gggaaccgga 480
aaagcgggcc agcagcctgc aagaaaaaga ttgaatttcg gtcagactgg agacgcagac 540
tccgtacctg acccccagcc tctcggacag ccaccagcag ccccctctgg tctgggaact 600
aatacgatgg cttcaggcag tggcgcacca atggcagaca ataacgaggg cgccgacgga 660
gtgggtaatt cctcgggaaa ttggcattgc gattccacat ggatgggcga cagagtcatc 720
accaccagca cccgaacttg ggccctgccc acctacaaca accatctcta caagcaaatc 780
tccagccaat caggagccag caacgacaac cactactttg gctacagcac cccttggggg 840
tattttgact tcaacagatt ccactgccac ttttcaccac gtgactggca aagactcatc 900
aacaacaact ggggattccg gcccaagaga ctcaacttca agctctttaa cattcaagtc 960
aaagaggtca cgcagaatga cggtacgacg acgattgcca ataaccttac cagcacggtt 1020
caggtgttta ctgactcgga gtaccagctc ccgtacgtcc tcggctcggc gcatcaagga 1080
tgcctcccgc cgttcccagc agacgtcttc atggtgccac agtatggata cctcaccctg 1140
aacaacggga gtcaggcagt aggacgctct tcattttact gcctggagta ctttccttct 1200
cagatgctgc gtaccggaaa caactttacc ttcagctaca cctttgagga cgttcctttc 1260
cacagcagct acgctcacag ccagagtttg gaccgtctca tgaatcctct catcgaccag 1320
tacctgtatt acttgagcag aacaaacact ccaagcggaa ccaccacgca gtccaggctt 1380
cagttttctc aggccggagc aagtgacatt cgggaccagt ctaggaactg gcttcctgga 1440
ccctgttacc gccagcagcg agtatcaaag acatctgcgg ataacaacaa cagtgaatac 1500
tcgtggactg gagctaccaa gtaccacctc aatggcagag actctctggt gaatccgggc 1560
ccggccatgg ccagccacaa ggacgatgaa gaaaagtttt ttcctcagag cggggttctc 1620
atctttggga agcaaggctc agagaaaaca aatgtggaca ttgaaaaggt catgattaca 1680
gacgaagagg aaatcaggac caccaatccc gtggctacgg agcagtatgg ttctgtatct 1740
accaacctgc agggcggcaa cacacaagca gctaccgcag atgtcaacac acaaggcgtt 1800
cttccaggca tggtctggca ggacagagac gtgtacctgc aggggcccat ctgggcaaag 1860
attccacaca cggacggaca ttttcacccc tctcccctca tgggcggatt cggacttaaa 1920
caccctcctc cacagattct catcaagaac accccggtac ctgcgaatcc ttcgaccacc 1980
ttcagtgcgg caaagtttgc ttctttcatc acacagtatt ccacggggca ggtcagcgtg 2040
gagatcgagt gggagctgca gaaggagaac agcaaacgct ggaatcccga gatccagtac 2100
acttccaact acaacaaatc tgttaatgtg gactttactg ttgacactaa tggcgtgtat 2160
tcagagcctc gccccattgg caccagatac ctgactcgta atctgtaa 2208
<210> 17
<211> 2208
<212> DNA
<213> 腺相关病毒, hu.26
<400> 17
atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaataaga 60
cagtggtgga agctcaaacc tggcccacca ccaccaaagc ccgcagagcg gcataaggac 120
gacagcaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac 180
aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 240
cggcagctcg acagcggaga caacccgtac ctcaagtaca accacgccga cgcggagttt 300
caggagcgtc ttaaagaaga tacgtctttt gggggcaacc tcggacgagc agtcttccag 360
gccaaaaaga ggattcttga acctctgggc ctggttgagg aacctgttaa gacggctccg 420
ggaaaaaaga ggccggtaga gcactctcct gcggagccag actcctcctc gggaaccgga 480
aaagcgggcc agcagcctgc aagaaagaga ttgaattttg gtcagactgg agacgcagac 540
tcagtacctg acccccagcc tctcggacag ccaccagcag ccccctctgg tctgggaact 600
aatacgatgg cttcaggcag tggcgcacca atggcagaca ataacgaggg cgccgacgga 660
gtgggtaatt cctcgggaaa ttggcattgc gattccacat ggatgggcga cagagtcatc 720
accaccagca cccgcacctg ggccctgccc acctacaaca accatctgta caagcaaatc 780
tccagccagt ctggagccag caacgacaac cactactttg gctacagcac cccctggggg 840
tattttgact tcaacagatt ccactgccac ttctccccac gtgactggca aagactcatc 900
aacaacaact ggggattccg gcccaagaga ctcagcttca agctctttaa cattcaagtc 960
aaagaggtca cgcagaatga cggtacgacg acgattgcca ataaccttac cagcacggtt 1020
caggtgttta ctgactcgga gtaccagctc ccgtacgtcc tcggctcggc gcatcaagga 1080
tgcctcccgc cgttcccagc agacgtcttc atggtgccac agtatggata cctcaccctg 1140
aacaacggca gtcaggcggt aggacgctct tccttttact gcctggagta ctttccttct 1200
cagatgcttc gtaccggaaa caactttacc ttcagctaca cctttgaaga cgttcctttc 1260
catagcagct acgctcacag ccaaagtctg gaccgtctca tgaatcctct catcgaccag 1320
tacctgtatt acttgagcag aacaaacact ccaagcggaa ccaccacgat gtccaggctt 1380
cagttttctc aggccggagc aagtgacatt cgggaccagt ctagaaactg gcttcctgga 1440
ccctgttacc gccagcagcg agtatcaaag acagctgcgg acaacaacaa cagtgattac 1500
tcgtggactg gagctaccaa gtaccacctc aatggaagag actctctggt gaatccgggc 1560
ccagctatgg ccagccacaa ggacgatgaa gaaaaatatt ttcctcagag cggggttctc 1620
atctttggaa aacaagactc gggaaaaact aatgtggaca ttgaaaaggt tatgattaca 1680
gacgaagagg aaatcaggac caccaatccc gtggctacgg agcagtatgg ttctgtatct 1740
accaacctcc agagcggcaa cacacaagca gctacctcag atgtcaacac acaaggcgtt 1800
cttccaggca tggtctggca ggacagagac gtgtacctgc aggggcccat ctgggcaaag 1860
attccacaca cggacggaca ttttcacccc tctcccctca tgggcggatt cggacttaaa 1920
caccctcctc cacaaattct catcaagaac accccggtac ctgcgaatcc ttcgaccact 1980
ttcagtgcgg caaagtttgc ttccttcatc acacagtact ccacggggca ggtcagcgtg 2040
gagatcgagt gggagctgca gaaggagaac agcaaacgct ggaatcccga aattcagtac 2100
acttccaact acaacaaatc tgttaatgtg gactttactg tggacactaa tggtgtgtat 2160
tcagagcctc gccccattgg caccagatac ctgactcgta atctgtaa 2208
<210> 18
<211> 2217
<212> DNA
<213> 腺相关病毒, hu.37
<400> 18
atggctgctg acggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60
gagtggtggg acctgaaacc tggagccccc aagcccaagg ccaaccagca gaagcaggac 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 aagctgctaa gacggctcct 420
ggaaagaaga gaccggtaga accgtcacct cagcgttccc ccgactcctc cacgggcatc 480
ggcaagaaag gccagcagcc cgctaaaaag agactgaact ttggtcagac tggcgactca 540
gagtcagtcc ccgaccctca accaatcgga gaaccaccag caggcccctc tggtctggga 600
tctggtacaa tggctgcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 660
ggagtgggta gttcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720
atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780
atatccaatg ggacatcggg aggaagcacc aacgacaaca cctacttcgg ctacagcacc 840
ccctgggggt attttgactt caacagattc cactgccact tctcaccacg tgactggcag 900
cgactcatca acaacaactg gggattccgg ccaaaaagac tcagcttcaa gctcttcaac 960
atccaggtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taaccttacc 1020
agcacgattc aggtatttac ggactcggaa taccagctgc cgtacgtcct cggctccgcg 1080
caccagggct gcctgcctcc gttcccggcg gacgtcttca tgattcccca gtacggctac 1140
cttacactga acaatggaag tcaagccgta ggccgttcct ccttctactg cctggaatat 1200
tttccatctc aaatgctgcg aactggaaac aattttgaat tcagctacac cttcgaggac 1260
gtgcctttcc acagcagcta cgcacacagc cagagcttgg accgactgat gaatcctctc 1320
atcgaccagt acctgtacta cttatccaga actcagtcca caggaggaac tcaaggtacc 1380
cagcaattgt tattttctca agctgggcct gcaaacatgt cggctcaggc taagaactgg 1440
ctacctggac cttgctaccg gcagcagcga gtctctacga cactgtcgca aaacaacaac 1500
agcaactttg cttggactgg tgccaccaaa tatcacctga acggaagaga ctctttggta 1560
aatcccggtg tcgccatggc aacccacaag gacgacgagg aacgcttctt cccgtcgagt 1620
ggagtcctga tgttcggaaa acagggtgct ggaagagaca atgtggacta cagcagcgtt 1680
atgctaacca gcgaagaaga aattaaaacc actaaccccg tagccacaga acaatacggt 1740
gtggtggctg acaacttgca gcaaaccaat acagggccta ttgtgggaaa tgtcaacagc 1800
caaggagcct tacctggcat ggtctggcag aaccgagacg tgtacctgca gggtcccatc 1860
tgggccaaga ttcctcacac ggacggcaac ttccaccctt caccgctaat gggaggattt 1920
ggactgaagc acccacctcc tcagatcctg atcaagaaca cgccggtacc tgcggatcct 1980
ccaacaacgt tcagccaggc gaaattggct tccttcatta cgcagtacag caccggacag 2040
gtcagcgtgg aaatcgagtg ggagctgcag aaggagaaca gcaaacgctg gaacccagag 2100
attcagtaca cttcaaacta ctacaaatct acaaatgtgg actttgctgt caatacagag 2160
ggaacttatt ctgagcctcg ccccattggt actcgttacc tcacccgtaa tctgtaa 2217
<210> 19
<211> 2205
<212> DNA
<213> 腺相关病毒, hu.53
<400> 19
atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaataaga 60
cagtggtgga agctcaaacc tggcccacca ccaccaaagc ccgcagagcg gcataaggac 120
gacagcaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac 180
aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa ggcctacgac 240
cggcagctcg acagcggaga caacccgtac ctcaagtaca accacgccga cgcggagttt 300
caggagcgtc ttaaagaaga tacgtctttt gggggcaacc tcggacgagc agtcttccag 360
gcgaaaaaga gggttcttga acctctgggc ctggttgagg aacctgttaa gacggctccg 420
ggaaaaaaga ggccggtaga gcactctcct gcggagccag actcctcctc gggaaccgga 480
aaagcgggcc agcagcctgc aagaaaaaga ctgaatttcg gtcagactgg agacgcagac 540
tccgtacctg acccccagcc tctcagacag ccaccagcag cccccacaag tttgggatct 600
actacaatgg ctacaggcag tggcgcacca atggcagaca ataacgaggg tgccgatgga 660
gtgggtaatt cctcaggaaa ttggcattgc gattcccaat ggctgggcga cagagtcatc 720
accaccagca cccgaacctg ggccctgccc acctacaaca accaccttta caagcaaatc 780
tccagccaat caggagcctc aaacgacaac cactactttg gctacagcac cccctggggg 840
tattttgact tcaacagatt ccactgccac ttttcaccac gtgactggca aagactcatc 900
aacaacaact ggggattccg acccaagaga ctcaacttca agctctttaa cattcaagtc 960
aaagaggtca cgcagaatga cggtacgacg acgattgcca ataaccttac cagcacggtt 1020
caggtgttta ctgactcgga gtaccagctc ccgtacgtcc tcggctcggc gcatcaagga 1080
tgcctcccgc cgtttccagc ggacgtcttc atggtcccac agtatggata cctcaccctg 1140
aacaacggga gtcaggcggt aggacgctct tccttttact gcctggagta ctttccttct 1200
cagatgctgc gtactggaaa caactttcag ttcagctaca cttttgaaga cgtgcctttc 1260
cacagcagct acgctcacag ccagagtttg gatcggctga tgaatcctct gatcgaccag 1320
tacctgtatt atctaaacag aacacaaaca gctagtggaa ctcagcagtc tcggctactg 1380
tttagccaag ctggacccac aagcatgtct cttcaagcta aaaactggct gcctggaccg 1440
tgttatcgcc agcagcgttt gtcaaagcag gcaaacgaca acaacaacag caactttccc 1500
tggactggag ctaccaagta ctacctcaat ggcagagact ctttggtgaa cccgggcccg 1560
gccatggcca gccacaagga cgatgaagaa aagtttttcc ccatgcatgg aaccctaata 1620
tttggtaaag aaggaacaaa tgctaccaac gcggaattgg aaaatgtcat gattacagat 1680
gaagaggaaa tcaggaccac caatcccgtg gctacagagc agtacggata tgtgtcaaat 1740
aatttgcaaa actcaaatac tgctgcaagt actgaaactg tgaatcacca aggagcatta 1800
cctggtatgg tgtggcagga tcgagacgtg tacctgcagg gacccatttg ggccaagatt 1860
cctcacaccg atggacactt tcatccttct ccactgatgg gaggttttgg actcaaacac 1920
ccgcctcctc agattatgat caaaaacact cccgttccag ccaatcctcc cacaaacttc 1980
agttctgcca agtttgcttc cttcatcaca cagtattcca cgggacaggt cagcgtggag 2040
atcgagtggg agctgcagaa ggagaacagc aaacgctgga atcccgaaat tcagtacact 2100
tccaactaca acaaatctgt taatgtggac tttactgtgg acactaatgg tgtgtattca 2160
gagcctcgcc ccattggcac cagatacctg actcgtaatc tgtaa 2205
<210> 20
<211> 2217
<212> DNA
<213> 猕猴腺相关病毒, rh.39
<400> 20
atggctgctg acggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60
gagtggtggg acctgaaacc tggagccccc aagcccaagg ccaaccagca gaagcaggac 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 aagctgctaa gacggctcct 420
ggaaagaaga gaccggtaga accgtcacct cagcgttccc ccgactcctc cacgggcatc 480
ggcaagaaag gccagcagcc cgctaaaaag agactgaact ttggtcagac tggcgactca 540
gagtcagtcc ccgaccctca accaatcgga gaaccaccag caggcccctc tggtctggga 600
tctggtacaa tggctgcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 660
ggagtgggta gttcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720
atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780
atatccaatg ggacatcggg aggaagcacc aacgacaaca cctacttcgg ctacagcacc 840
ccctgggggt attttgactt caacagattc cactgccact tctcaccacg tgactggcag 900
cgactcatca acaacaactg gggattccgg ccaaaaagac tcagcttcaa gctcttcaac 960
atccaggtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taaccttacc 1020
agcacgattc aggtatttac ggactcggaa taccagctgc cgtacgtcct cggctccgcg 1080
caccagggct gcctgcctcc gttcccggcg gacgtcttca tgattcccca gtacggctac 1140
cttacactga acaatggaag tcaagccgta ggccgttcct ccttctactg cctggaatat 1200
tttccatctc aaatgctgcg aactggaaac aattttgaat tcagctacac cttcgaggac 1260
gtgcctttcc acagcagcta cgcacacagc cagagcttgg accgactgat gaatcctctc 1320
atcgaccagt acctgtacta cttatccaga actcagtcca caggaggaac tcaaggtacc 1380
cagcaattgt tattttctca agctgggcct gcaaacatgt cggctcaggc taagaactgg 1440
ctacctggac cttgctaccg gcagcagcga gtctctacga cactgtcgca aaacaacaac 1500
agcaactttg cttggactgg tgccaccaaa tatcacctga acggaagaga ctctttggta 1560
aatcccggtg tcgccatggc aacccacaag gacgacgagg aacgcttctt cccgtcgagt 1620
ggagtcctga tgtttggaaa acagggtgct ggaagagaca atgtggacta cagcagcgtt 1680
atgctaacca gcgaagaaga aattaaaacc actaaccctg tagccacaga acaatacggt 1740
gtggtggctg ataacttgca gcaaaccaat acggggccta ttgtgggaaa tgtcaacagc 1800
caaggagcct tacctggcat ggtctggcag aaccgagacg tgtacctgca gggtcccatc 1860
tgggccaaga ttcctcacac ggacggcaac ttccaccctt caccgctaat gggaggattt 1920
ggactgaagc acccacctcc tcagatcctg atcaagaaca cgccggtacc tgcggatcct 1980
ccaacaacgt tcagccaggc gaaattggct tccttcatta cgcagtacag caccggacag 2040
gtcagcgtgg aaatcgagtg ggagctgcag aaggagaaca gcaaacgctg gaacccagag 2100
attcagtaca cttcaaacta ctacaaatct acaaatgtgg actttgctgt caatacagag 2160
ggaacttatt ctgagcctcg ccccattggt actcgttacc tcacccgtaa tctgtaa 2217
<210> 21
<211> 2211
<212> DNA
<213> 猕猴腺相关病毒, rh.43
<400> 21
atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60
gagtggtggg acttgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120
gacggccggg gcctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180
aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240
cagcagctcg aagcgggtga caatccgtac ctgcggtata accacgccga cgccgagttt 300
caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360
gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420
ggaaagaaga gaccagtaga gcagtcaccc caagaaccag actcctcctc gggcatcggc 480
aagaaaggcc aacagcccgc cagaaaaaga ctcaattttg gccagactgg cgactcagag 540
tcagttccag accctcaacc tctcggagaa cctccagcag cgccctctgg tgtgggacct 600
aatacaatgg ctgcaggcgg tggcgcacca atggcagaca ataacgaagg cgccgacgga 660
gtgggtagtt cctcgggaaa ttggcattgc gattccacat ggctgggcga cagagtcatc 720
accaccagca cccgaacctg ggccctgccc acctacaaca accacctcta caagcaaatc 780
tccaacggga catcgggagg agccaccaac gacaacacct acttcggcta cagcaccccc 840
tgggggtatt ttgactttaa cagattccac tgccactttt caccacgtga ctggcagcga 900
ctcatcaaca acaactgggg attccggccc aagagactca gcttcaagct cttcaacatc 960
caggtcaagg aggtcacgca gaatgaaggc accaagacca tcgccaataa cctcaccagc 1020
accatccagg tgtttacgga ctcggagtac cagctgccgt acgttctcgg ctctgcccac 1080
cagggctgcc tgcctccgtt cccggcggac gtgttcatga ttccccagta cggctaccta 1140
acactcaaca acggtagtca ggccgtggga cgctcctcct tctactgcct ggaatacttt 1200
ccttcgcaga tgctgagaac cggcaacaac ttccagttta cttacacctt cgaggacgtg 1260
cctttccaca gcagctacgc ccacagccag agcttggacc ggctgatgaa tcctctgatt 1320
gaccagtacc tgtactactt gtctcggact caaacaacag gaggcacggc aaatacgcag 1380
actctgggct tcagccaagg tgggcctaat acaatggcca atcaggcaaa gaactggctg 1440
ccaggaccct gttaccgcca acaacgcgtc tcaacgacaa ccgggcaaaa caacaatagc 1500
aactttgcct ggactgctgg gaccaaatac catctgaatg gaagaaattc attggctaat 1560
cctggcatcg ctatggcaac acacaaagac gacgaggagc gttttttccc agtaacggga 1620
tcctgttttt ggcaacaaaa 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 acagaaggaa aacagcaagc gctggaaccc cgagatccag 2100
tacacctcca actactacaa atctacaagt gtggactttg ctgttaatac agaaggcgtg 2160
tactctgaac cccgccccat tggcacccgt tacctcaccc gtaatctgta a 2211
<210> 22
<211> 2217
<212> DNA
<213> 猕猴腺相关病毒, rh.46
<400> 22
atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60
gagtggtggg acctgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120
gacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180
aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240
cagcagctca aagcgggtga caatccgtac ctgcggtata atcacgccga cgccgagttt 300
caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag 360
gccaagaagc gggttctcga acctctcggt ctggttgagg aaggcgctaa gacggctcct 420
ggaaagaaga gaccggtaga gccgtcacca cagcgttccc ccgactcctc cacgggcatc 480
ggcaagaaag gccagcagcc cgccagaaag agactcaatt tcggtcagac tggcgactca 540
gagtcagtcc ccgaccctca acctatcgga gaacctccag cagcgccctc tagtgtggga 600
tctggtacaa tggctgcagg cggtggcgca ccaatggcag acaataacga aggtgccgac 660
ggagtgggta gttcctcggg aaattggcat tgcgattcca catggctggg cgacagagtc 720
atcaccacca gcacccgaac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780
atctccaacg ggacctcggg aggcagcacc aacgacaaca cctactttgg ctacagcacc 840
ccctgggggt attttgactt taacagattc cactgccact tctcaccacg tgactggcag 900
cgactcatca acaacaactg gggattccgg cccaagagac tcagcttcaa gctcttcaac 960
atccaggtca aagaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taacctcacc 1020
agcaccatcc aggtgtttac ggactcggaa taccagctgc cgtacgtcct cggctctgcc 1080
caccagggct gcctgcctcc gttcccggcg gacgtcttca tgattcctca gtacggctac 1140
ctgactctca acaacggtag tcaggccgtg ggacgttcct ccttctactg cctggagtac 1200
ttcccctctc agatgctgag aacgggcaac aacttttcct tcagctacac tttcgaggac 1260
gtgcctttcc acagcagcta cgcgcacagc cagagtttgg acaggctgat gaatcctctc 1320
atcgaccagt acctgtacta cctgtcaaga acccagtcta cgggaggcac agcgggaacc 1380
cagcagttgc tgttttctca ggccgggcct agcaacatgt cggctcaggc cagaaactgg 1440
ctgcctggac cctgctacag acagcagcgc gtctccacga cactgtcgca aaacaacaac 1500
agcaactttg cctggactgg tgccaccaag tatcatctga acggcagaga ctctctggtg 1560
aatccgggcg tcgccatggc aaccaacaag gacgacgagg accgcttctt cccatccagc 1620
ggcatcctca tgtttggcaa gcagggagct ggaaaagaca acgtggacta tagcaacgtg 1680
atgctaacca gcgaggaaga aatcaaggcc accaaccccg tggccacaga acagtatggc 1740
gtggtggctg ataacctaca gcagcaaaac accgctccta ttgtgggggc cgtcaacagc 1800
cagggagcct tacctggcat ggtctggcag aaccgggacg tgtacctgca gggtcctatt 1860
tgggccaaga ttcctcacac agatggcaac tttcacccgt ctcctttaat gggcggcttt 1920
ggacttaaac atccgcctcc tcagatcctc atcaaaaaca ctcctgttcc tgcggatcct 1980
ccaacagcgt tcaaccaggc caagctgaat tctttcatca cgcagtacag caccggacaa 2040
gtcagcgtgg agatcgagtg ggagctgcag aaggagaaca gcaagcgctg gaacccagag 2100
attcagtata cttccaacta ctacaaatct acaaatgtgg actttgctgt taatactgag 2160
ggtgtttact ctgagcctcg ccccattggc actcgttacc tcacccgtaa tctgtaa 2217
<210> 23
<211> 735
<212> PRT
<213> 腺相关病毒血清型2的衣壳蛋白
<400> 23
Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser
1 5 10 15
Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro
20 25 30
Lys Pro Ala Glu Arg His Lys Asp Asp Ser 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 Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp
65 70 75 80
Arg Gln Leu Asp Ser 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 Val Leu Glu Pro
115 120 125
Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg
130 135 140
Pro Val Glu His Ser Pro Val Glu Pro Asp Ser Ser Ser Gly Thr Gly
145 150 155 160
Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr
165 170 175
Gly Asp Ala Asp Ser Val Pro Asp Pro Gln Pro Leu Gly Gln Pro Pro
180 185 190
Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Thr Gly Ser Gly
195 200 205
Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser
210 215 220
Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met 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 Gln Ser Gly Ala Ser Asn Asp Asn His Tyr
260 265 270
Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His
275 280 285
Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp
290 295 300
Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val
305 310 315 320
Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu
325 330 335
Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr
340 345 350
Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp
355 360 365
Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser
370 375 380
Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser
385 390 395 400
Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu
405 410 415
Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg
420 425 430
Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr
435 440 445
Asn Thr Pro Ser Gly Thr Thr Thr Gln Ser Arg Leu Gln Phe Ser Gln
450 455 460
Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly
465 470 475 480
Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ser Ala Asp Asn Asn
485 490 495
Asn Ser Glu Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly
500 505 510
Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp
515 520 525
Asp Glu Glu Lys Phe Phe Pro Gln Ser Gly Val Leu Ile Phe Gly Lys
530 535 540
Gln Gly Ser Glu Lys Thr Asn Val Asp Ile Glu Lys Val Met Ile Thr
545 550 555 560
Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr
565 570 575
Gly Ser Val Ser Thr Asn Leu Gln Arg Gly Asn Arg Gln Ala Ala Thr
580 585 590
Ala Asp Val Asn Thr Gln Gly Val Leu Pro Gly Met Val Trp Gln Asp
595 600 605
Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr
610 615 620
Asp Gly His 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 Asn
645 650 655
Pro Ser Thr Thr Phe Ser Ala Ala Lys Phe Ala 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
Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr
705 710 715 720
Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu
725 730 735
<210> 24
<211> 728
<212> PRT
<213> cy.5的衣壳蛋白
<400> 24
Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Gly 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 Arg Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro
50 55 60
Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp
65 70 75 80
Lys Gln Leu Glu Gln Gly Asp Asn Pro Tyr Leu Lys 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 Ile Glu Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Asn Gly Gln
145 150 155 160
Pro Pro Ala Lys Lys Lys Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu
165 170 175
Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser
180 185 190
Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Met Ala
195 200 205
Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp
210 215 220
His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr
225 230 235 240
Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile
245 250 255
Ser Ser Gln Ser Gly Ala Thr Asn Asp Asn His Phe Phe Gly Tyr Ser
260 265 270
Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser
275 280 285
Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro
290 295 300
Arg Lys Leu Arg Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr
305 310 315 320
Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile
325 330 335
Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser
340 345 350
Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile
355 360 365
Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ser Val Gly
370 375 380
Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg
385 390 395 400
Thr Gly Asp Asn Phe Glu Phe Ser Tyr Thr Phe Glu Glu Val Pro Phe
405 410 415
His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro
420 425 430
Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala Arg Thr Gln Ser Thr Thr
435 440 445
Gly Ser Thr Arg Glu Leu Gln Phe His Gln Ala Gly Pro Asn Thr Met
450 455 460
Ala Glu Gln Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln
465 470 475 480
Arg Leu Ser Lys Asn Ile Asp Ser Asn Asn Asn Ser Asn Phe Ala Trp
485 490 495
Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr Asn
500 505 510
Pro Gly Val Ala Met Ala Thr Asn Lys Asp Asp Glu Asp Gln Phe Phe
515 520 525
Pro Ile Asn Gly Val Leu Val Phe Gly Lys Thr Gly Ala Ala Asn Lys
530 535 540
Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu Ile Lys Thr
545 550 555 560
Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn Leu
565 570 575
Gln Ser Ser Thr Ala Gly Pro Gln Thr Gln Thr Val Asn Ser Gln Gly
580 585 590
Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly
595 600 605
Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser
610 615 620
Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu
625 630 635 640
Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr Pro
645 650 655
Ala Lys Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser
660 665 670
Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn
675 680 685
Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val Glu
690 695 700
Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Pro Arg Pro Ile Gly
705 710 715 720
Thr Arg Tyr Leu Thr Arg Asn Leu
725
<210> 25
<211> 738
<212> PRT
<213> 猕猴腺相关病毒, rh.10的衣壳蛋白
<400> 25
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 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 Ser 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 Asn 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 Glu Phe Ser Tyr
405 410 415
Gln 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 Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu
450 455 460
Phe Ser Gln Ala Gly Pro Asn Asn Met Ser Ala Gln Ala Lys Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met
530 535 540
Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser 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 Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Ala Ala
580 585 590
Pro Ile Val Gly Ala 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 Ser Gln Ala Lys Leu Ala 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 Asn Val Asp Phe Ala Val Asn Thr Asp
705 710 715 720
Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg
725 730 735
Asn Leu
<210> 26
<211> 728
<212> PRT
<213> 猕猴腺相关病毒, rh.13的衣壳蛋白
<400> 26
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 Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp
65 70 75 80
Lys Gln Leu Glu Gln Gly Asp Asn Pro Tyr Leu Lys 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 Ile Glu Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gln
145 150 155 160
Gln Pro Ala Lys Lys Lys Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu
165 170 175
Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser
180 185 190
Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Met Ala
195 200 205
Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp
210 215 220
His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr
225 230 235 240
Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile
245 250 255
Ser Ser Gln Ser Gly Ala Thr Asn Asp Asn His Phe Phe Gly Tyr Ser
260 265 270
Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser
275 280 285
Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro
290 295 300
Arg Lys Leu Arg Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr
305 310 315 320
Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile
325 330 335
Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser
340 345 350
Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile
355 360 365
Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ser Val Gly
370 375 380
Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg
385 390 395 400
Thr Gly Asn Asn Phe Glu Phe Ser Tyr Thr Phe Glu Glu Val Pro Phe
405 410 415
His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro
420 425 430
Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala Arg Thr Gln Ser Thr Thr
435 440 445
Gly Ser Thr Arg Glu Leu Gln Phe His Gln Ala Gly Pro Asn Thr Met
450 455 460
Ala Glu Gln Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln
465 470 475 480
Arg Leu Ser Lys Asn Ile Asp Ser Asn Asn Asn Ser Asn Phe Ala Trp
485 490 495
Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr Asn
500 505 510
Pro Gly Val Ala Met Ala Thr Asn Lys Asp Asp Glu Asp Gln Phe Phe
515 520 525
Pro Ile Asn Gly Val Leu Val Phe Gly Glu Thr Gly Ala Ala Asn Lys
530 535 540
Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu Ile Lys Thr
545 550 555 560
Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn Leu
565 570 575
Gln Ser Ser Thr Ala Gly Pro Gln Thr Gln Thr Val Asn Ser Gln Gly
580 585 590
Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly
595 600 605
Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser
610 615 620
Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu
625 630 635 640
Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr Pro
645 650 655
Ala Lys Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser
660 665 670
Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn
675 680 685
Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val Glu
690 695 700
Phe Ala Val Asn Asn Glu Gly Val Tyr Thr Glu Pro Arg Pro Ile Gly
705 710 715 720
Thr Arg Tyr Leu Thr Arg Asn Leu
725
<210> 27
<211> 736
<212> PRT
<213> 腺相关病毒血清型1的衣壳蛋白
<400> 27
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 Glu 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 Glu 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 Phe Gln Ser Ser Ser Thr Asp Pro Ala
580 585 590
Thr Gly Asp Val His Ala 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 Asn 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> 28
<211> 736
<212> PRT
<213> 腺相关病毒血清型3的衣壳蛋白
<400> 28
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 Val Pro Gln Pro
20 25 30
Lys Ala Asn Gln Gln His Gln Asp Asn Arg 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 Glu 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 Gln Glu Asp Thr Ser Phe Gly Gly
100 105 110
Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Ile Leu Glu Pro
115 120 125
Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Gly
130 135 140
Ala Val Asp Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Val Gly
145 150 155 160
Lys Ser Gly Lys Gln Pro Ala Arg 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 Ala Pro Thr Ser Leu Gly Ser Asn 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 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 Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr
260 265 270
Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His
275 280 285
Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp
290 295 300
Gly Phe Arg Pro Lys Lys Leu Ser Phe Lys Leu Phe Asn Ile Gln Val
305 310 315 320
Arg Gly Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu
325 330 335
Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr
340 345 350
Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp
355 360 365
Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser
370 375 380
Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser
385 390 395 400
Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Thr Phe Glu
405 410 415
Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg
420 425 430
Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg Thr
435 440 445
Gln Gly Thr Thr Ser Gly Thr Thr Asn Gln Ser Arg Leu Leu Phe Ser
450 455 460
Gln Ala Gly Pro Gln Ser Met Ser Leu Gln Ala Arg Asn Trp Leu Pro
465 470 475 480
Gly Pro Cys Tyr Arg Gln Gln Arg Leu Ser Lys Thr Ala Asn Asp Asn
485 490 495
Asn Asn Ser Asn Phe Pro Trp Thr Ala Ala Ser Lys Tyr His Leu Asn
500 505 510
Gly Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys
515 520 525
Asp Asp Glu Glu Lys Phe Phe Pro Met His Gly Asn Leu Ile Phe Gly
530 535 540
Lys Glu Gly Thr Thr Ala Ser Asn Ala Glu Leu Asp Asn Val Met Ile
545 550 555 560
Thr Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln
565 570 575
Tyr Gly Thr Val Ala Asn Asn Leu Gln Ser Ser Asn Thr Ala Pro Thr
580 585 590
Thr Gly Thr Val Asn His Gln 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 Met Ile Lys Asn Thr Pro Val Pro Ala
645 650 655
Asn Pro Pro Thr Thr Phe Ser Pro Ala 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 Ile Gln Tyr Thr Ser Asn
690 695 700
Tyr Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn 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> 29
<211> 736
<212> PRT
<213> 腺相关病毒血清型6的衣壳蛋白
<400> 29
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> 30
<211> 737
<212> PRT
<213> 腺相关病毒血清型7的衣壳蛋白
<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 Asp Leu Lys Pro Gly Ala Pro Lys Pro
20 25 30
Lys Ala Asn Gln Gln Lys Gln Asp Asn 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 Ala 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 Ser Val Gly Ser Gly Thr Val Ala Ala 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 Glu Thr Ala Gly Ser Thr Asn Asp Asn
260 265 270
Thr 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 Lys Leu Arg 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 Ile 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 Ser 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 Glu Phe Ser Tyr Ser
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 Ala
435 440 445
Arg Thr Gln Ser Asn Pro Gly Gly Thr Ala Gly Asn Arg Glu Leu Gln
450 455 460
Phe Tyr Gln Gly Gly Pro Ser Thr Met Ala Glu Gln Ala Lys Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Phe Arg Gln Gln Arg Val Ser Lys Thr Leu Asp
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
His Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Val Leu Ile
530 535 540
Phe Gly Lys Thr Gly Ala Thr Asn Lys Thr Thr Leu Glu Asn Val Leu
545 550 555 560
Met Thr Asn Glu Glu Glu Ile Arg Pro Thr Asn Pro Val Ala Thr Glu
565 570 575
Glu Tyr Gly Ile Val Ser Ser Asn Leu Gln Ala Ala Asn Thr Ala Ala
580 585 590
Gln Thr Gln Val Val Asn Asn Gln Gly Ala Leu Pro Gly Met Val Trp
595 600 605
Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro
610 615 620
His Thr Asp Gly Asn 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 Glu Val Phe Thr Pro Ala 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 Ile Gln Tyr Thr Ser
690 695 700
Asn Phe Glu Lys Gln Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly
705 710 715 720
Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn
725 730 735
Leu
<210> 31
<211> 738
<212> PRT
<213> 腺相关病毒血清型8的衣壳蛋白
<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 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> 32
<211> 735
<212> PRT
<213> 腺相关病毒, hu.13的衣壳蛋白
<400> 32
Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser
1 5 10 15
Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro
20 25 30
Lys Pro Ala Glu Arg His Lys Asp Asp Ser 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 Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp
65 70 75 80
Arg Gln Leu Asp Ser 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 Val Leu Glu Pro
115 120 125
Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg
130 135 140
Pro Val Glu His Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Thr Gly
145 150 155 160
Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr
165 170 175
Gly Asp Ala Asp Ser Val Pro Asp Pro Gln Pro Leu Gly Gln Pro Pro
180 185 190
Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Ser Gly Ser Gly
195 200 205
Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser
210 215 220
Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met 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 Gln Ser Gly Ala Ser Asn Asp Asn His Tyr
260 265 270
Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His
275 280 285
Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp
290 295 300
Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val
305 310 315 320
Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu
325 330 335
Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr
340 345 350
Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp
355 360 365
Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser
370 375 380
Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser
385 390 395 400
Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu
405 410 415
Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg
420 425 430
Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr
435 440 445
Asn Thr Pro Ser Gly Thr Thr Thr Gln Ser Arg Leu Gln Phe Ser Gln
450 455 460
Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly
465 470 475 480
Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ser Ala Asp Asn Asn
485 490 495
Asn Ser Glu Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly
500 505 510
Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp
515 520 525
Asp Glu Glu Lys Phe Phe Pro Gln Ser Gly Val Leu Ile Phe Gly Lys
530 535 540
Gln Gly Ser Glu Lys Thr Asn Val Asp Ile Glu Lys Val Met Ile Thr
545 550 555 560
Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr
565 570 575
Gly Ser Val Ser Thr Asn Leu Gln Gly Gly Asn Thr Gln Ala Ala Thr
580 585 590
Ala Asp Val Asn Thr Gln Gly Val Leu Pro Gly Met Val Trp Gln Asp
595 600 605
Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr
610 615 620
Asp Gly His 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 Asn
645 650 655
Pro Ser Thr Thr Phe Ser Ala Ala Lys Phe Ala 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
Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr
705 710 715 720
Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu
725 730 735
<210> 33
<211> 735
<212> PRT
<213> 腺相关病毒, hu.26的衣壳蛋白
<400> 33
Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser
1 5 10 15
Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro
20 25 30
Lys Pro Ala Glu Arg His Lys Asp Asp Ser 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 Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp
65 70 75 80
Arg Gln Leu Asp Ser 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 Ile Leu Glu Pro
115 120 125
Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg
130 135 140
Pro Val Glu His Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Thr Gly
145 150 155 160
Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr
165 170 175
Gly Asp Ala Asp Ser Val Pro Asp Pro Gln Pro Leu Gly Gln Pro Pro
180 185 190
Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Ser Gly Ser Gly
195 200 205
Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser
210 215 220
Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met 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 Gln Ser Gly Ala Ser Asn Asp Asn His Tyr
260 265 270
Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His
275 280 285
Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp
290 295 300
Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn Ile Gln Val
305 310 315 320
Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu
325 330 335
Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr
340 345 350
Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp
355 360 365
Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser
370 375 380
Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser
385 390 395 400
Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu
405 410 415
Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg
420 425 430
Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr
435 440 445
Asn Thr Pro Ser Gly Thr Thr Thr Met Ser Arg Leu Gln Phe Ser Gln
450 455 460
Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly
465 470 475 480
Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ala Ala Asp Asn Asn
485 490 495
Asn Ser Asp Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly
500 505 510
Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp
515 520 525
Asp Glu Glu Lys Tyr Phe Pro Gln Ser Gly Val Leu Ile Phe Gly Lys
530 535 540
Gln Asp Ser Gly Lys Thr Asn Val Asp Ile Glu Lys Val Met Ile Thr
545 550 555 560
Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr
565 570 575
Gly Ser Val Ser Thr Asn Leu Gln Ser Gly Asn Thr Gln Ala Ala Thr
580 585 590
Ser Asp Val Asn Thr Gln Gly Val Leu Pro Gly Met Val Trp Gln Asp
595 600 605
Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr
610 615 620
Asp Gly His 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 Asn
645 650 655
Pro Ser Thr Thr Phe Ser Ala Ala Lys Phe Ala 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
Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr
705 710 715 720
Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu
725 730 735
<210> 34
<211> 738
<212> PRT
<213> 腺相关病毒, hu.37的衣壳蛋白
<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 Ala 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 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 Ser 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 Glu Phe Ser 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 Ser Thr Gly Gly Thr Gln Gly Thr Gln Gln Leu Leu
450 455 460
Phe Ser Gln Ala Gly Pro Ala Asn Met Ser Ala Gln Ala Lys Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met
530 535 540
Phe Gly Lys Gln Gly Ala Gly Arg Asp Asn Val Asp Tyr Ser Ser 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 Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Thr Asn Thr Gly
580 585 590
Pro Ile Val Gly Asn 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 Ser Gln Ala Lys Leu Ala 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 Asn Val Asp Phe Ala Val Asn Thr Glu
705 710 715 720
Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg
725 730 735
Asn Leu
<210> 35
<211> 734
<212> PRT
<213> 腺相关病毒, hu.53的衣壳蛋白
<400> 35
Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser
1 5 10 15
Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro
20 25 30
Lys Pro Ala Glu Arg His Lys Asp Asp Ser 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 Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp
65 70 75 80
Arg Gln Leu Asp Ser 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 Val Leu Glu Pro
115 120 125
Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg
130 135 140
Pro Val Glu His Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Thr Gly
145 150 155 160
Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr
165 170 175
Gly Asp Ala Asp Ser Val Pro Asp Pro Gln Pro Leu Arg Gln Pro Pro
180 185 190
Ala Ala Pro Thr Ser Leu Gly Ser Thr Thr Met Ala Thr Gly Ser Gly
195 200 205
Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn 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 Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr
260 265 270
Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His
275 280 285
Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp
290 295 300
Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val
305 310 315 320
Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu
325 330 335
Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr
340 345 350
Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp
355 360 365
Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser
370 375 380
Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser
385 390 395 400
Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Thr Phe Glu
405 410 415
Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg
420 425 430
Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg Thr
435 440 445
Gln Thr Ala Ser Gly Thr Gln Gln Ser Arg Leu Leu Phe Ser Gln Ala
450 455 460
Gly Pro Thr Ser Met Ser Leu Gln Ala Lys Asn Trp Leu Pro Gly Pro
465 470 475 480
Cys Tyr Arg Gln Gln Arg Leu Ser Lys Gln Ala Asn Asp Asn Asn Asn
485 490 495
Ser Asn Phe Pro Trp Thr Gly Ala Thr Lys Tyr Tyr Leu Asn Gly Arg
500 505 510
Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp Asp
515 520 525
Glu Glu Lys Phe Phe Pro Met His Gly Thr Leu Ile Phe Gly Lys Glu
530 535 540
Gly Thr Asn Ala Thr Asn Ala Glu Leu Glu Asn Val Met Ile Thr Asp
545 550 555 560
Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr Gly
565 570 575
Tyr Val Ser Asn Asn Leu Gln Asn Ser Asn Thr Ala Ala Ser Thr Glu
580 585 590
Thr Val Asn His Gln Gly Ala Leu Pro Gly Met Val Trp Gln Asp Arg
595 600 605
Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp
610 615 620
Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His
625 630 635 640
Pro Pro Pro Gln Ile Met Ile Lys Asn Thr Pro Val Pro Ala Asn Pro
645 650 655
Pro Thr Asn Phe Ser Ser Ala Lys Phe Ala Ser Phe Ile Thr Gln Tyr
660 665 670
Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu
675 680 685
Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Asn
690 695 700
Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr Ser
705 710 715 720
Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu
725 730
<210> 36
<211> 738
<212> PRT
<213> 猕猴腺相关病毒, rh.39的衣壳蛋白
<400> 36
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 Ala 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 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 Ser 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 Glu Phe Ser 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 Ser Thr Gly Gly Thr Gln Gly Thr Gln Gln Leu Leu
450 455 460
Phe Ser Gln Ala Gly Pro Ala Asn Met Ser Ala Gln Ala Lys Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met
530 535 540
Phe Gly Lys Gln Gly Ala Gly Arg Asp Asn Val Asp Tyr Ser Ser 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 Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Thr Asn Thr Gly
580 585 590
Pro Ile Val Gly Asn 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 Ser Gln Ala Lys Leu Ala 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 Asn Val Asp Phe Ala Val Asn Thr Glu
705 710 715 720
Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg
725 730 735
Asn Leu
<210> 37
<211> 736
<212> PRT
<213> 猕猴腺相关病毒, rh.43的衣壳蛋白
<400> 37
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 Glu 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 Lys Gly Gln Gln Pro Ala Arg 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 Ala Pro Ser Gly Val Gly Pro Asn Thr Met Ala Ala Gly Gly Gly
195 200 205
Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser
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 Gly Thr Ser Gly Gly Ala Thr Asn Asp Asn
260 265 270
Thr 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 Ser Phe Lys Leu Phe Asn Ile
305 310 315 320
Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala Asn
325 330 335
Asn Leu Thr Ser Thr Ile Gln Val Phe Thr 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 Gln Phe Thr 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
Arg Thr Gln Thr Thr Gly Gly Thr Ala Asn Thr Gln Thr Leu Gly Phe
450 455 460
Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu
465 470 475 480
Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln
485 490 495
Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu
500 505 510
Asn Gly Arg Asn Ser Leu Ala Asn Pro Gly Ile Ala Met Ala Thr His
515 520 525
Lys Asp Asp Glu Glu Arg Phe Phe Pro Val Thr Gly Ser Cys Phe Trp
530 535 540
Gln 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 Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu
725 730 735
<210> 38
<211> 738
<212> PRT
<213> 猕猴腺相关病毒, rh.46的衣壳蛋白
<400> 38
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 Ile Gly Glu Pro
180 185 190
Pro Ala Ala Pro Ser Ser Val Gly Ser Gly 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 Ser 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 Ser Phe Ser 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 Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu
450 455 460
Phe Ser Gln Ala Gly Pro Ser Asn Met Ser Ala Gln Ala Arg Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
Asn Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Ile Leu Met
530 535 540
Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Asn Val
545 550 555 560
Met Leu Thr Ser Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr
565 570 575
Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala
580 585 590
Pro Ile Val Gly Ala 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 Ala Phe Asn Gln Ala 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 Asn 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> 39
<211> 738
<212> PRT
<213> 猕猴腺相关病毒, rh.2的衣壳蛋白
<400> 39
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 His 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 Ile Gly Glu Pro
180 185 190
Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly 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 Ser 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 Asn 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 Pro 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 Glu Phe Ser 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 Ser Thr Gly Gly Thr Gln Gly Thr Gln Gln Leu Leu
450 455 460
Phe Ser Gln Ala Gly Pro Ala Asn Met Ser Ala Gln Ala Lys Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met
530 535 540
Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser 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 Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Thr Asn Gly Ala
580 585 590
Pro Ile Val 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 Val Lys Asn Thr Pro Val
645 650 655
Pro Ala Asp Pro Pro Thr Thr Phe Ser Gln Ala Lys Leu Ala 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 Asn Val Asp Phe Ala Val Asn Thr Glu
705 710 715 720
Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg
725 730 735
Asn Leu
<210> 40
<211> 729
<212> PRT
<213> 猕猴腺相关病毒, rh.37的衣壳蛋白
<400> 40
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 Ile Asp Ser Pro Asp Ser Ser Thr Gly Ile Gly Lys Lys Gly Gln
145 150 155 160
Gln Pro Ala Lys Lys Lys Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu
165 170 175
Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro Ala Ala Pro Ser
180 185 190
Ser Val Gly Ser Gly Thr Met Ala Ala Gly Gly Gly Ala Pro Thr Ala
195 200 205
Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp
210 215 220
His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr
225 230 235 240
Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile
245 250 255
Ser Ser Ser Ser Ser Gly Ala Thr Asn Asp Asn His Tyr Phe Gly Tyr
260 265 270
Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe
275 280 285
Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg
290 295 300
Pro Lys Lys Leu Arg Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val
305 310 315 320
Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr
325 330 335
Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly
340 345 350
Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met
355 360 365
Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ser Val
370 375 380
Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu
385 390 395 400
Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Ser Phe Glu Asp Val Pro
405 410 415
Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn
420 425 430
Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ala Arg Thr Gln Ser Thr
435 440 445
Thr Gly Ser Thr Arg Glu Leu Gln Phe His Gln Ala Gly Pro Asn Thr
450 455 460
Met Ala Glu Gln Ser Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln
465 470 475 480
Gln Arg Leu Ser Lys Asn Leu Asp Phe Asn Asn Asn Ser Asn Phe Ala
485 490 495
Trp Thr Ala Ala Thr Lys Tyr His Leu Asn Gly Arg Asn Ser Leu Thr
500 505 510
Asn Pro Gly Ile Pro Met Ala Thr Asn Lys Asp Asp Glu Asp Gln Phe
515 520 525
Phe Pro Ile Asn Gly Val Leu Val Phe Gly Lys Thr Gly Ala Ala Asn
530 535 540
Lys Thr Thr Leu Glu Asn Val Leu Met Thr Ser Glu Glu Glu Ile Lys
545 550 555 560
Thr Thr Asn Pro Val Ala Thr Glu Glu Tyr Gly Val Val Ser Ser Asn
565 570 575
Leu Gln Ser Ser Thr Ala Gly Pro Gln Ser Gln Thr Ile Asn Ser Gln
580 585 590
Gly Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln
595 600 605
Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro
610 615 620
Ser Pro Leu Met Gly Gly Phe Gly Leu Glu His Pro Pro Pro Gln Ile
625 630 635 640
Leu Ile Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Glu Val Phe Thr
645 650 655
Pro Ala Lys Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val
660 665 670
Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp
675 680 685
Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Asn Asn Val
690 695 700
Glu Phe Ala Val Asn Pro Asp Gly Val Tyr Thr Glu Pro Arg Pro Ile
705 710 715 720
Gly Thr Arg Tyr Leu Thr Arg Asn Leu
725
<210> 41
<211> 736
<212> PRT
<213> 猕猴腺相关病毒, rh.8的衣壳蛋白
<400> 41
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 Ala Pro Ser Gly Leu Gly Pro Asn 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 Ser
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 Gly Thr Ser Gly Gly Ser Thr Asn Asp Asn
260 265 270
Thr 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 Glu Gly Thr Lys Thr Ile Ala Asn
325 330 335
Asn Leu Thr Ser Thr Val Gln Val Phe Thr 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 Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn
370 375 380
Gly Ser Gln Ala Leu 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 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 Val
435 440 445
Arg Thr Gln Thr Thr Gly Thr Gly Gly Thr Gln Thr Leu Ala Phe Ser
450 455 460
Gln Ala Gly Pro Ser Ser Met Ala Asn Gln Ala Arg Asn Trp Val Pro
465 470 475 480
Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Asn Gln Asn
485 490 495
Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Ala Lys Phe Lys Leu Asn
500 505 510
Gly Arg Asp Ser Leu Met Asn Pro Gly Val Ala Met Ala Ser His Lys
515 520 525
Asp Asp Asp Asp Arg Phe Phe Pro Ser Ser Gly Val Leu Ile Phe Gly
530 535 540
Lys Gln Gly Ala Gly Asn Asp Gly Val Asp Tyr Ser Gln Val Leu Ile
545 550 555 560
Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Glu
565 570 575
Tyr Gly Ala Val Ala Ile Asn Asn Gln Ala Ala Asn Thr Gln Ala Gln
580 585 590
Thr Gly Leu Val His Asn Gln Gly Val Ile 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 Leu Thr Phe Asn Gln Ala 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 Asn Val Asp 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> 42
<211> 735
<212> PRT
<213> 腺相关病毒, hu.29的衣壳蛋白
<400> 42
Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser
1 5 10 15
Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro
20 25 30
Lys Pro Ala Glu Arg His Lys Asp Asp Ser 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 Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp
65 70 75 80
Arg Gln Leu Asp Ser 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 Val Leu Glu Pro
115 120 125
Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg
130 135 140
Pro Val Glu His Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Thr Gly
145 150 155 160
Lys Ser Gly Asn Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr
165 170 175
Gly Asp Ser Asp Ser Val Pro Asp Pro Gln Pro Leu Gly Gln Pro Pro
180 185 190
Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Thr Gly Ser Gly
195 200 205
Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser
210 215 220
Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met 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 Gln Ser Gly Ala Ser Asn Asp Asn His Tyr
260 265 270
Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His
275 280 285
Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp
290 295 300
Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val
305 310 315 320
Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu
325 330 335
Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr
340 345 350
Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp
355 360 365
Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser
370 375 380
Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Gly Tyr Phe Pro Ser
385 390 395 400
Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu
405 410 415
Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg
420 425 430
Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr
435 440 445
Asn Thr Pro Ser Gly Thr Thr Thr Gln Ser Arg Leu Gln Phe Ser Gln
450 455 460
Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly
465 470 475 480
Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ser Ala Asp Asn Asn
485 490 495
Asn Ser Glu Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly
500 505 510
Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp
515 520 525
Asp Glu Glu Lys Phe Phe Pro Gln Ser Gly Val Leu Ile Phe Gly Lys
530 535 540
Gln Gly Pro Glu Lys Thr Asn Val Asp Ile Glu Lys Val Met Ile Thr
545 550 555 560
Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr
565 570 575
Gly Ser Val Ser Thr Asn Leu Gln Ser Gly Asn Thr Gln Ala Ala Thr
580 585 590
Ala Asp Val Asn Thr Gln Gly Val Leu Pro Gly Met Val Trp Gln Asp
595 600 605
Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr
610 615 620
Asp Gly His 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 Asn
645 650 655
Pro Ser Thr Thr Phe Ser Ala Ala Lys Phe Ala 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
Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr
705 710 715 720
Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu
725 730 735
<210> 43
<211> 738
<212> PRT
<213> 猕猴腺相关病毒, rh.64的衣壳蛋白
<400> 43
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 Ile Gly Glu Pro
180 185 190
Pro Ala Ala Pro Ser Ser Val Gly Ser Gly 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 Ser 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 Ser Phe Ser 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 Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu
450 455 460
Phe Ser Gln Ala Gly Pro Ser Asn Met Ser Ala Gln Ala Arg Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
Asn Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Ile Leu Met
530 535 540
Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Asn 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 Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala
580 585 590
Pro Ile Val Gly Ala 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 Ala Phe Asn Gln Ala Lys Leu Asn Ser Phe
660 665 670
Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Val Trp Glu
675 680 685
Leu Gln Lys Glu Asn Ser Lys Arg Arg Asn Pro Glu Ile Gln Tyr Thr
690 695 700
Ser Asn Tyr Tyr Lys Ser Thr Asn 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> 44
<211> 737
<212> PRT
<213> 猕猴腺相关病毒, rh.48的衣壳蛋白
<400> 44
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 Ala 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 Ile Gly Glu Pro
180 185 190
Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly
195 200 205
Gly Ala Pro Met Ala Asp Asn Asn Lys 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 Gln Ser Ala Gly Ser Thr Asn Asp Asn
260 265 270
Val 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 Ser
290 295 300
Asn Trp Gly Phe Arg Pro Lys Lys 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 Ser 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 Ala
435 440 445
Arg Thr Gln Ser Asn Ala Gly Gly Thr Ala Gly Asn Arg Glu Leu Gln
450 455 460
Phe Tyr Gln Gly Gly Pro Thr Thr Met Ala Glu Gln Ala Lys Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Phe Arg Gln Gln Arg Val Ser Lys Thr Leu Asp
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Ile
530 535 540
Phe Gly Lys Thr Gly Ala Ala Asn Lys Thr Thr Leu Glu Asn Val Leu
545 550 555 560
Met Thr Asn Glu Glu Glu Ile Arg Pro Thr Asn Pro Val Ala Thr Glu
565 570 575
Glu Tyr Gly Thr Val Ser Ser Asn Leu Gln Ala Ala Asn Thr Ala Ala
580 585 590
Gln Thr Gln Val Val Asn Asn Gln Gly Ala Leu Pro Gly Met Val Trp
595 600 605
Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro
610 615 620
His Thr Asp Gly Asn 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 Glu Val Phe Thr Pro Ala 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 Ile Gln Tyr Thr Ser
690 695 700
Asn Phe Asp Lys Gln Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly
705 710 715 720
Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn
725 730 735
Leu
<210> 45
<211> 736
<212> PRT
<213> 腺相关病毒, hu.44的衣壳蛋白
<400> 45
Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser
1 5 10 15
Glu Gly Ile Arg Gln Trp Trp Lys Leu Arg Pro Gly Pro Pro Pro Pro
20 25 30
Lys Pro Ala Glu Arg His Lys Asp Asp Ser 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 Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp
65 70 75 80
Arg Gln Leu Asp Ser 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 Val Leu Glu Pro
115 120 125
Leu Gly Leu Val Glu Glu Gly Ala Glu Thr Ala Pro Gly Lys Lys Arg
130 135 140
Pro Val Glu Gln Ser Pro Gln Gly 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 Glu 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 Pro 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 Glu 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 Phe Gln Ser Ser Ser Thr Asp Pro Ala
580 585 590
Thr Gly Asp Val His Ala Met Gly Ala Leu Pro Gly Met Val Trp Gln
595 600 605
Gly 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 Asn 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> 46
<211> 735
<212> PRT
<213> ch.5的衣壳蛋白
<400> 46
Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser
1 5 10 15
Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro
20 25 30
Lys Pro Asn Gln Gln His Arg Asp Asp Ser 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 Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp
65 70 75 80
His Gln Leu Lys Gln Gly Asp Asn Pro Tyr Leu Lys 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 Ala Val Lys Thr Ala Pro Gly Lys Lys Arg
130 135 140
Pro Ile Glu Gln Ser Pro Ala Glu Pro Asp Ser Ser Ser Gly Ile Gly
145 150 155 160
Lys Ser Gly Gln 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 Asn 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 Ser
210 215 220
Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met 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 Glu Ser Gly Ala Thr Asn Asp Asn His Tyr
260 265 270
Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His
275 280 285
Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp
290 295 300
Gly Phe Arg Pro Lys Lys Leu Asn Phe Lys Leu Phe Asn Ile Gln Val
305 310 315 320
Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu
325 330 335
Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr
340 345 350
Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp
355 360 365
Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser
370 375 380
Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser
385 390 395 400
Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu
405 410 415
Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg
420 425 430
Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Lys Thr
435 440 445
Gln Gly Thr Ser Gly Thr Thr Gln Gln Ser Arg Leu Gln Phe Ser Gln
450 455 460
Ala Gly Pro Ser Ser Met Ala Gln Gln Ala Lys Asn Trp Leu Pro Gly
465 470 475 480
Pro Ser Tyr Arg Gln Gln Arg Met Ser Lys Thr Ala Asn Asp Asn Asn
485 490 495
Asn Ser Glu Phe Ala Trp Thr Ala Ala Thr Lys Tyr Tyr Leu Asn Gly
500 505 510
Arg Asn Ser Leu Val Asn Pro Gly Pro Pro Met Ala Ser His Lys Asp
515 520 525
Asp Glu Glu Lys Tyr Phe Pro Met His Gly Asn Leu Ile Phe Gly Lys
530 535 540
Gln Gly Thr Gly Thr Thr Asn Val Asp Ile Glu Ser Val Leu Ile Thr
545 550 555 560
Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr
565 570 575
Gly Gln Val Ala Thr Asn His Gln Ser Gln Asn Thr Thr Ala Ser Tyr
580 585 590
Gly Ser Val Asp Ser Gln Gly Ile Leu Pro Gly Met Val Trp Gln Asp
595 600 605
Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr
610 615 620
Asp Gly His 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 Asn
645 650 655
Pro Ala Thr Thr Phe Thr Pro Gly Lys Phe Ala 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
Asn Lys Ser Val Asn Val Glu Phe Thr Val Asp Ala Asn Gly Val Tyr
705 710 715 720
Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu
725 730 735
<210> 47
<211> 737
<212> PRT
<213> 猕猴腺相关病毒, rh.67的衣壳蛋白
<400> 47
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 Leu Gln Ala Lys Lys Arg Val 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 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 Ile Gly Glu Pro
180 185 190
Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala 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 Gln Ser Ala Gly Ser Thr Asn Asp Asn
260 265 270
Val 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 Lys 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 Ser 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 Ala
435 440 445
Arg Thr Gln Ser Asn Ala Gly Gly Thr Ala Gly Asn Arg Glu Leu Gln
450 455 460
Phe Tyr Gln Gly Gly Pro Thr Thr Met Ala Glu Gln Ala Lys Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Phe Arg Gln Gln Arg Val Ser Lys Thr Leu Asp
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Ile
530 535 540
Phe Gly Lys Thr Gly Ala Ala Asn Lys Thr Thr Leu Glu Asn Val Leu
545 550 555 560
Met Thr Asn Glu Glu Glu Ile Arg Pro Thr Asn Pro Val Ala Thr Glu
565 570 575
Glu Tyr Gly Thr Val Ser Ser Asn Leu Gln Ala Ala Asn Thr Ala Ala
580 585 590
Gln Thr Gln Val Val Asn Asn Gln Gly Ala Leu Pro Gly Met Val Trp
595 600 605
Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro
610 615 620
His Thr Asp Gly Asn 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 Glu Val Phe Thr Pro Ala 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 Ile Gln Tyr Thr Ser
690 695 700
Asn Phe Asp Lys Gln Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly
705 710 715 720
Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn
725 730 735
Leu
<210> 48
<211> 738
<212> PRT
<213> 猕猴腺相关病毒, rh.58的衣壳蛋白
<400> 48
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 Ala 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 Ile Gly Glu Pro
180 185 190
Pro Ala Ala Pro Ser Ser Val Gly Ser Gly 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 Ser 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 Ser Phe Ser 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 Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu
450 455 460
Phe Ser Gln Ala Gly Pro Ser Asn Met Ser Ala Gln Ala Arg Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
Asn Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Ile Leu Met
530 535 540
Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Asn 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 Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala
580 585 590
Pro Ile Val Gly Ala 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 Ser Thr Pro Val
645 650 655
Pro Ala Asp Pro Pro Thr Ala Phe Asn Gln Ala 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 Cys Trp Asn Pro Glu Ile Gln Tyr Thr
690 695 700
Ser Asn Tyr Tyr Lys Ser Thr Asn 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> 49
<211> 737
<212> PRT
<213> 猕猴腺相关病毒, rh.54的衣壳蛋白
<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 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 Ala 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 Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala 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 Gln Ser Ala Gly Ser Thr Asn Asp Asn
260 265 270
Val 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 Lys 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 Ser Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe
385 390 395 400
Pro Ser Gln Val 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 Ala
435 440 445
Arg Thr Gln Ser Asn Pro Gly Gly Thr Ser Gly Asn Arg Glu Leu Gln
450 455 460
Phe Tyr Gln Gly Gly Pro Ser Thr Met Ala Glu Gln Ala Lys Asn Trp
465 470 475 480
Leu Pro Gly Pro Cys Phe Arg Gln Gln Arg Val Ser Lys Thr Leu Asp
485 490 495
Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His
500 505 510
Leu Asn Gly Arg Asn Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr
515 520 525
His Lys Asp Asp Glu Asp Arg Phe Phe Pro Ser Ser Gly Val Leu Ile
530 535 540
Phe Gly Lys Thr Gly Ala Thr Asn Lys Thr Thr Leu Glu Asn Val Leu
545 550 555 560
Met Thr Asn Glu Glu Glu Ile Arg Pro Thr Asn Pro Val Ala Thr Glu
565 570 575
Glu Tyr Gly Ile Val Ser Ser Asn Leu Gln Ala Ala Asn Thr Ala Ala
580 585 590
Gln Thr Gln Val Val Asn Asn Gln Gly Ala Leu Pro Gly Met Val Trp
595 600 605
Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro
610 615 620
His Thr Asp Gly Asn 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 Glu Val Phe Thr Pro Ala 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 Ile Gln Tyr Thr Ser
690 695 700
Asn Phe Asp Lys Gln Thr Gly Val Asp Phe Ala Val Asp Ser Gln Gly
705 710 715 720
Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn
725 730 735
Leu
<210> 50
<211> 736
<212> PRT
<213> 腺相关病毒, hu.48的衣壳蛋白
<400> 50
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 Thr Ser Thr Gly Ala Ser Asn Asp Asn His
260 265 270
Tyr Phe Gly Tyr Gly 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 Glu 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 Glu 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 Val Ala Ser His Lys
515 520 525
Asp Asp Glu Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Gly
530 535 540
Lys Glu Ser Ala Gly Ala Ser Ser 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 Phe Gln Ser Ser Ser Thr Asp Pro Ala
580 585 590
Thr Gly Asp Val His Ala 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 Asn 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

Claims (13)

1.一种腺相关病毒(AAV)载体，具有AAVrh.64衣壳，所述衣壳由经修饰的SEQ ID NO:43所示氨基酸序列构成，所述经修饰的氨基酸序列与SEQ ID NO:43所示氨基酸序列的区别在于其中第697位的原精氨酸改为色氨酸。
2.如权利要求1所述的病毒载体，所述病毒载体携有编码基因产物的转基因，所述转基因受调控序列的调控，所述调控序列指导所述转基因在宿主细胞内表达。
3.一种组合物，包含权利要求1或2所述的AAV载体和生理相容载体。
4.如权利要求1或2所述的AAV载体或如权利要求3所述的组合物用于制造用于向对象递送基因产物的产品的用途。
5.如权利要求4所述的用途，所述基因产物选自鸟氨酸转氨甲酰酶、精氨基琥珀酸合成酶、精氨基琥珀酸裂合酶、精氨酸酶、延胡索酰乙酰乙酸水解酶、氨甲酰磷酸合成酶I、支链酮酸脱羧酶、异戊酰-CoA脱氢酶、丙酰-CoA羧化酶、甲基丙二酰CoA变位酶、戊二酰-CoA脱氢酶(GCDH)、丙酮酸羧酸盐、肝磷酸化酶、磷酸化酶激酶和甘氨酸脱羧酶。
6.如权利要求4所述的用途，所述基因产物是免疫球蛋白，所述免疫球蛋白选自免疫球蛋白IgG、IgM、IgA、IgD、IgE，嵌合免疫球蛋白，人源化抗体和单链抗体。
7.如权利要求4所述的用途，所述基因产物是因子IX或因子VIII。
8.如权利要求4所述的用途，所述基因产物是抗肌萎缩蛋白基因产物。
9.如权利要求8所述的用途，所述抗肌萎缩蛋白基因产物是小-抗肌萎缩蛋白或微-抗肌萎缩蛋白。
10.如权利要求4所述的用途，所述基因产物选自苯丙氨酸羟化酶、α-1抗胰蛋白酶、葡萄糖-6-磷酸酶、胆色素原脱氨酶、胱硫醚β-合成酶、β-葡糖苷酶和β-葡糖醛酸糖苷酶(GUSB)。
11.如权利要求4所述的用途，所述基因产物选自低密度脂蛋白(LDL)受体、高密度脂蛋白(HDL)受体、极低密度脂蛋白(VLDL)受体、清除受体、糖皮质激素受体、雌激素受体、维生素D受体、核受体和囊性纤维化跨膜传导调节蛋白(CFTR)序列。
12.一种核酸分子，其中的核酸序列编码经修饰的AAVrh.64衣壳，所述衣壳由经修饰的SEQ ID NO:43所示氨基酸序列构成，所述经修饰的氨基酸序列与SEQ ID NO:43所示氨基酸序列的区别在于其中第697位的原精氨酸改为色氨酸。
13.如权利要求12所述的核酸分子，其为质粒。
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