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1. 发明申请

WO2005033320A1 PACKAGING CELLS FOR RECOMBINANT ADENOVIRUS 审中-公开
标题翻译：用于重组腺病毒的包装细胞
公开(公告)号：WO2005033320A1
公开(公告)日：2005-04-14
申请号：PCT/EP2004/052428
申请日：2004-10-04
申请人： CRUCELL HOLLAND B.V. , VOGELS, Ronald , HAVENGA, Menzo, Jans, Emco , ZUIJDGEEST, David A.T.M.
发明人： VOGELS, Ronald , HAVENGA, Menzo, Jans, Emco , ZUIJDGEEST, David A.T.M.
IPC分类号： C12N15/86
CPC分类号： C07K14/005 , C12N7/00 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352 , C12N2830/38
摘要： In the absence of substantial sequence overlap between a recombinant adenoviral vector and the genome of a packaging cell, helper dependent El-containing particles (HDEP) can be formed at low frequency. The invention provides means and methods reducing or preventing the generation of HDEP. To this purpose, novel packaging cells and methods of making these are provided.
摘要翻译：在重组腺病毒载体和包装细胞的基因组之间不存在实质的序列重叠的情况下，可以以低频形成辅助依赖性的含有El的颗粒（HDEP）。本发明提供减少或防止HDEP产生的方法和方法。为此，提供了新颖的包装电池及其制造方法。

2. 发明申请

WO03002735A3 METHODS, VECTORS, CELL LINES AND KITS FOR SELECTING NUCLEIC ACIDS HAVING A DESIRED FEATURE 审中-公开
标题翻译：用于选择具有所需特征的核酸的方法，载体，细胞系和试剂盒
公开(公告)号：WO03002735A3
公开(公告)日：2003-05-30
申请号：PCT/CA0200997
申请日：2002-06-28
申请人： PHENOGENE THERAPEUTIQUES INC , LANCTOT CHRISTIAN , GINGRAS ROCK , GAUMOND MARIE-HELENE
发明人： LANCTOT CHRISTIAN , GINGRAS ROCK , GAUMOND MARIE-HELENE
IPC分类号： C12N9/00 , C12N15/85 , C12N15/86 , C12N15/00
CPC分类号： C12N9/00 , C12N15/85 , C12N15/86 , C12N2770/36143 , C12N2800/30 , C12N2830/002 , C12N2830/38 , C12N2830/55
摘要： Methods, vectors, cell lines and kits for the screening and identification of nucleic acids are described. The invention is based on the use of a site-specific recombinase to excise, from an expression vector into which an exogenous nucleic acid having a desired feature has been inserted, a region of the vector which is excisable by site-specific recombination. Insertion into the vector of a nucleic acid having a desired feature, such as nucleic acids capable of changing the expression of cellular genes or the state of cellular metabolism or signaling pathways, triggers the synthesis and/or activity of a site specific recombinase, the action of the recombinase allowing an easy selection of the expression vector containing the exogenous nucleic acid having a desired feature.
摘要翻译：描述了用于筛选和鉴定核酸的方法，载体，细胞系和试剂盒。本发明基于使用位点特异性重组酶从具有所需特征的外源核酸插入的表达载体中切除可通过位点特异性重组可切除的载体区域。插入到具有期望特征的核酸的载体中，例如能够改变细胞基因表达的核酸或细胞代谢或信号通路的状态，触发了位点特异性重组酶的合成和/或活性，该作用的重组酶允许容易地选择含有具有期望特征的外源核酸的表达载体。

3. 发明申请

WO0125465A9 ADENO-ASSOCIATED VIRUSES AND USES THEREOF 审中-公开
标题翻译： ADENO相关病毒及其用途
公开(公告)号：WO0125465A9
公开(公告)日：2002-11-21
申请号：PCT/US0027863
申请日：2000-10-06
申请人： UNIV IOWA RES FOUND , ENGELHARDT JOHN F , DUAN DONGSHENG , YAN ZIYANG
发明人： ENGELHARDT JOHN F , DUAN DONGSHENG , YAN ZIYANG
IPC分类号： C12N15/09 , A61K35/76 , A61K38/00 , A61K48/00 , A61P43/00 , C12N5/10 , C12N7/01 , C12N15/864
CPC分类号： C12N15/86 , A61K48/00 , C12N2750/14143 , C12N2800/108 , C12N2830/38 , C12N2840/203 , C12N2840/44 , C12N2840/445
摘要： The invention provides an isolated and purified DNA molecule comprising at least one DNA segment, a biologically active subunit or variant thereof, of a circular intermediate of adeno-associated virus, which DNA segment confers increased episomal stability, persistence or abundance of the isolated DNA molecule in a host cell. The invention also provides a composition comprising at least two adeno-associated virus vectors.
摘要翻译：本发明提供了分离和纯化的DNA分子，其包含腺伴随病毒的环状中间体的至少一个DNA区段，其生物活性亚单位或变体，该DNA区段赋予分离的DNA分子的增加的附加体稳定性，持久性或丰度在宿主细胞中。本发明还提供包含至少两个腺相关病毒载体的组合物。

4. 发明申请

WO0142481A3 CANINE ADENOVIRUS VECTORS FOR THE TRANSFER OF GENES INTO TARGET CELLS 审中-公开
标题翻译：用于将基因转移到目标细胞中的犬腺病毒载体
公开(公告)号：WO0142481A3
公开(公告)日：2002-05-10
申请号：PCT/EP0012792
申请日：2000-12-06
申请人： GENETHON III , INST NAT SANTE RECH MED , KREMER ERIC , CHILLON RODRIGUEZ MIGUEL , SOUDAIS CLAIRE , BOUTIN SYLVIE , PELTEKIAN ELISE , GARCIA LUIS , VINCENT NATHALIE , DANOS OLIVIER
发明人： KREMER ERIC , CHILLON RODRIGUEZ MIGUEL , SOUDAIS CLAIRE , BOUTIN SYLVIE , PELTEKIAN ELISE , GARCIA LUIS , VINCENT NATHALIE , DANOS OLIVIER
IPC分类号： A61K48/00 , C12N15/86 , C12N15/861 , C12N5/16
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10343 , C12N2800/30 , C12N2830/38 , C12N2830/42
摘要： The invention relates to a Canine Adenovirus (CAV) vector obtainable by a process comprising the following steps: a) co-transforming E. coli cells having recBC sbcBC phenotype by a first plasmid and a pre-transfer plasmid in conditions enabling their recombination by homologous recombination, in order to generate a transfer plasmid devoid from a functional E1 coding region, comprising the desired recombinant vector genome, wherein the first plasmid comprises the Inverted Terminal Regions (ITR) and the Packaging Signal ( psi ) sequences of a CAV genome, and the pre-transfer plasmid includes the sequence whose insertion in the vector genome is desired, flanked by sequences homologous to sequences of the first plasmid surrounding the region of the first plasmid where the modification is desired; b) isolating a DNA fragment essentially comprising the recombinant vector genome by enzyme restriction; c) transfecting DK28Cre cells (CNCM I-2293) that are rendered able to transcomplement this recombinant vector genome; d) recovering and purifying the recombinant adenoviral particles produced. The obtained vector may be used for the transfer of any gene of interest in target cells, especially in neuronal cells.
摘要翻译：本发明涉及通过包括以下步骤的方法获得的犬腺病毒（CAV）载体：a）通过第一质粒和预转移质粒共转化具有recBC sbcBC表型的大肠杆菌细胞在能够通过同源重组进行重组的条件下，以产生不含功能性E1编码区的转移质粒，其包含所需的重组载体基因组，其中第一质粒包含反向末端区（ITR）和包装信号（psi） CAV基因组的序列和预转移质粒包括其中需要在载体基因组中插入的序列，其侧翼是与期望修饰的第一质粒的区域周围的第一质粒的序列同源的序列; b）通过酶限制分离基本上包含重组载体基因组的DNA片段; c）转染能够反式实现该重组载体基因组的DK28Cre细胞（CNCM I-2293）; d）回收和纯化所产生的重组腺病毒颗粒。获得的载体可用于转移目标细胞中的任何感兴趣的基因，特别是在神经元细胞中。

5. 发明申请

WO01075127A2 CLONING SYSTEM USED IN THE CONSTRUCTION OF HOMOLOGOUS RECOMBINATION VECTORS 审中-公开
标题翻译：克隆与同源重组的构建
公开(公告)号：WO01075127A2
公开(公告)日：2001-10-11
申请号：PCT/DE2001/001133
申请日：2001-03-22
IPC分类号： C12N15/63 , C12N15/90
CPC分类号： C12N15/63 , C12N15/902 , C12N2800/30 , C12N2830/38 , C12N2840/203
摘要： The invention relates to a novel cloning system that consists of a vector and adapter system that substantially simplifies the construction of homologous recombination vectors used for the mutagenesis of genes in living eukaryotic cells. The invention further relates to a method for producing homologous recombination vectors as well as to the use of said cloning system for modifying the genome at defined loci in eukaryotic cells, especially in embryonic stem cells.
摘要翻译：本发明涉及一种由一个矢量和适配器系统，其显著简化了用于在活的真核细胞中的基因的诱变同源重组载体的构建的新的克隆系统。此外，本发明涉及一种用于制备同源重组载体的方法。此外，本发明涉及使用克隆系统，以便在特定的基因座中的真核细胞来改变，特别是胚胎干细胞，基因组中。

6. 发明申请

WO0075354A2 ADENOVIRAL VECTORS ENCODING INTERFERON AND THEIR USE IN GENE THERAPY 审中-公开
标题翻译：编码干扰素及其在基因治疗中的使用的腺病毒载体
公开(公告)号：WO0075354A2
公开(公告)日：2000-12-14
申请号：PCT/EP0004875
申请日：2000-05-29
申请人： ANGELETTI P IST RICHERCHE BIO , PALOMBO FABIO , MONICA NICOLA , CILIBERTO GENNARO
发明人： PALOMBO FABIO , LA MONICA NICOLA , CILIBERTO GENNARO
IPC分类号： A61K48/00 , C07K14/56 , C12N15/20 , C12N15/861 , C07K14/555
CPC分类号： C12N15/86 , A61K48/00 , C07K14/56 , C12N2710/10343 , C12N2830/003 , C12N2830/008 , C12N2830/38 , C12N2830/42
摘要： Helper dependent adenoviral vectors encoding interferon (IFN) provide high levels of IFN in the serum, even when produced in the liver, to achieve a long-term therapeutically effective dosage, and allow for repeat administration to patients.
摘要翻译：编码干扰素（IFN）的辅助依赖性腺病毒载体即使在肝脏中产生时也能提供高水平的IFN，以达到长期的治疗有效剂量，并允许对患者重复施用。

7. 发明申请

WO9955132A3 GENERATION OF PACKAGING SYSTEM FOR HUMAN RECOMBINANT ADENOVIRAL VECTORS 审中-公开
标题翻译：人类重组腺病毒载体包装系统的生成
公开(公告)号：WO9955132A3
公开(公告)日：2000-04-06
申请号：PCT/NL9900235
申请日：1999-04-23
申请人： INTROGENE BV
发明人： VOGELS RONALD , BOUT ABRAHAM
IPC分类号： C12N15/09 , A61K48/00 , C07K14/075 , C12N5/10 , C12N7/00 , C12N7/01 , C12N15/861 , C12R1/01 , C12N15/86 , C12N15/00
CPC分类号： C12N7/00 , A61K48/00 , C07K14/005 , C12N15/86 , C12N2710/10322 , C12N2710/10343 , C12N2710/10352 , C12N2830/00 , C12N2830/15 , C12N2830/38 , C12N2830/60
摘要： The invention discloses novel means and methods for the generation of adenovirus vector. One method of the invention entails a method for generating an adenovirus vector comprising welding together two nucleic acid molecules whereby said molecules comprise partially overlapping sequences capable of combining with each other allowing the generation of a physically linked nucleic acid comprising at least two functional adenovirus inverted terminal repeats, a functional encapsulation signal and a nucleic acid of interest or functional parts, derivatives and/or analogues thereof. The invention further discloses nucleic acid molecules for generation adenovirus vectors.
摘要翻译：本发明公开了用于产生腺病毒载体的新颖方法和方法。本发明的一个方法需要一种产生腺病毒载体的方法，包括将两个核酸分子焊接在一起，由此所述分子包含能够彼此组合的部分重叠的序列，从而产生包含至少两个功能性腺病毒反向末端的物理连接的核酸重复，功能性封装信号和感兴趣的核酸或其功能部分，衍生物和/或类似物。本发明还公开了用于产生腺病毒载体的核酸分子。

8. 发明申请

WO99043843A1 A SIMPLIFIED SYSTEM FOR GENERATING RECOMBINANT ADENOVIRUSES 审中-公开
标题翻译：用于产生重组腺病毒的简化系统
公开(公告)号：WO99043843A1
公开(公告)日：1999-09-02
申请号：PCT/US1999/004062
申请日：1999-02-25
IPC分类号： C07K14/075 , C12N15/861 , C12N15/86 , C12N5/10 , C12N7/00 , C12N15/00 , C12R1/01
CPC分类号： C12N15/86 , C07K14/005 , C12N2710/10322 , C12N2710/10343 , C12N2830/38
摘要： Recombinant adenoviruses provide a versatile system for gene expression studies and therapeutic applications. This invention describes a strategy which simplifies the generation and production of such viruses. A recombinant adenoviral plasmid is generated with a minimum of enzymatic manipulations, employing homologous recombination in bacteria rather than in eucaryotic cells. Following transfections of such plasmids into a mammalian packaging cell line, viral production can be conveniently followed with the aid of green fluorescent protein, encoded by a gene incorporated into the viral backbone. Homogeneous viruses can be obtained from this procedure without plaque purification. This system expedites the process of generating and testing recombinant adenoviruses.
摘要翻译：重组腺病毒为基因表达研究和治疗应用提供了多功能的系统。本发明描述了一种简化这种病毒生成和生产的策略。通过最少的酶操作产生重组腺病毒质粒，在细菌中而不是在真核细胞中使用同源重组。在将这些质粒转染到哺乳动物包装细胞系之后，可以方便地利用由掺入病毒骨架的基因编码的绿色荧光蛋白来辅助病毒生产。可以从该程序获得均一的病毒，无需进行噬斑纯化。该系统加速了重组腺病毒的产生和检测过程。

9. 发明申请

WO98054345A1 MINI-ADENOVIRAL VECTOR 审中-公开
标题翻译：微型腺病毒载体
公开(公告)号：WO98054345A1
公开(公告)日：1998-12-03
申请号：PCT/US1998/010330
申请日：1998-05-19
IPC分类号： A01K67/027 , A61K38/00 , A61K48/00 , C07K14/755 , C12N15/34 , C12N15/85 , C12N15/861 , C12N15/86 , A61K35/76 , C12N5/10 , C12N7/01
CPC分类号： C12N15/86 , A01K67/0275 , A01K67/0276 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2267/0337 , A01K2267/0393 , A61K38/00 , A61K48/00 , C07K14/755 , C12N15/8509 , C12N2710/10343 , C12N2800/108 , C12N2800/30 , C12N2830/003 , C12N2830/008 , C12N2830/15 , C12N2830/38 , C12N2830/42 , C12N2830/85 , C12N2840/203 , C12N2840/206
摘要： This invention is related to adenoviral (Ad) vectors and their applications in the field of genetic medicine, including gene transfer, gene therapy, and gene vaccination. More specifically, this invention is related to the Ad vectors that carry the minimal cis-element of the Ad genome (mini-Ad vector) and are capable of delivering transgenes and/or heterologous DNA up to 36 kb. The generation and propagation of the mini-Ad vectors requires trans-complementation of a packaging-attenuated and replication-defective helper Ad (helper) in an Ad helper cell line. This invention further comprises a methodology for generating a mini-adenoviral (mini-Ad) vector for use in gene therapy of hemophilia and animal test systems for in vivo evaluation of the Ad vectors. More specifically, this invention describes factor VIII(FVIII) Ad vectors that only contain minimal cis-element of the Ad genome (so-called mini-Ad) and comprise a human FVIII cDNA with other supporting DNA elements up to 36 kb. The FVIII mini-Ad can be generated and preferentially amplified through the assistance of a packaging-attenuated helper Ad and a helper cell line. This invention also reports designs and methods for producing transgenic mouse models that can be used for in vivo testing the mini-Ad.
摘要翻译：本发明涉及腺病毒（Ad）载体及其在遗传医学领域的应用，包括基因转移，基因治疗和基因疫苗接种。更具体地，本发明涉及携带Ad基因组（mini-Ad载体）的最小顺式元件的Ad载体，并能够将转基因和/或异源DNA递送至36kb。迷你Ad载体的产生和繁殖需要Ad辅助细胞系中包装减毒和复制缺陷型辅助Ad（辅助细胞）的互补。本发明还包括用于产生用于血友病的基因治疗的微型腺病毒（小型-Ad）载体和用于Ad载体的体内评估的动物测试系统的方法。更具体地，本发明描述了仅包含Ad基因组的最小顺式元件（所谓的mini-Ad）的因子VIII（FVIII）Ad载体，并且包含具有高达36kb的其他支持DNA元件的人FVIII cDNA。 FVIII mini-Ad可以通过包装衰减的辅助Ad和辅助细胞系的帮助产生并优先放大。本发明还报道了可用于体内测试小型Ad的转基因小鼠模型的设计和方法。

10. 发明申请

WO1998005344A1 BACTERIOPHAGE-MEDIATED GENE THERAPY 审中-公开
标题翻译：细菌介导的基因治疗
公开(公告)号：WO1998005344A1
公开(公告)日：1998-02-12
申请号：PCT/US1997012928
申请日：1997-07-03
申请人： BRIGHAM AND WOMEN'S HOSPITAL, INC. , SARKAR, Saumyendra, N. , KUPPER, Thomas, S. , DUBIN, Daniel, B.
发明人： BRIGHAM AND WOMEN'S HOSPITAL, INC.
IPC分类号： A61K35/76
CPC分类号： C07K14/005 , A61K47/6901 , A61K48/00 , C07K14/4707 , C07K14/755 , C07K2319/00 , C12N15/86 , C12N2795/10322 , C12N2795/10343 , C12N2800/202 , C12N2830/008 , C12N2830/38 , C12N2830/42 , C12N2830/85 , C12N2840/203 , C12N2840/44
摘要： An improved method for delivering an exogenous gene, e.g., a therapeutic polynucleotide, to a mammalian cell is provided. The method involves using a bacteriophage as a vector to deliver the exogenous gene to a pre-selected target cell. The bacteriophage contains exogenous genetic material that can be transcribed and, optionally, translated in a mammalian cell and includes on its surface a ligand that binds to a receptor on the target cell. The bacteriophage is incapable of injecting the exogenous genetic material into the mammalian cell. The bacteriophages are useful for gene therapy applications and for producing exogenous gene products in vitro.
摘要翻译：提供了将外源基因（例如治疗性多核苷酸）递送至哺乳动物细胞的改进方法。该方法包括使用噬菌体作为载体将外源基因递送到预先选择的靶细胞。噬菌体含有外源遗传物质，其可被转录并且任选地在哺乳动物细胞中翻译，并且在其表面上包括与靶细胞上的受体结合的配体。噬菌体不能将外源遗传物质注入到哺乳动物细胞中。噬菌体可用于基因治疗应用和用于在体外产生外源基因产物。

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