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1. 发明申请

WO2009009798A3 ALLELIC EXCHANGE MUTAGENESIS IN MAP 审中-公开
标题翻译：地图中的等位交换致突变
公开(公告)号：WO2009009798A3
公开(公告)日：2009-07-30
申请号：PCT/US2008069999
申请日：2008-07-14
申请人： UNIV WASHINGTON STATE , DAVIS WILLIAM C , HAMILTON MARY JO , DAHL JOHN , PARK KUN TAEK
发明人： DAVIS WILLIAM C , HAMILTON MARY JO , DAHL JOHN , PARK KUN TAEK
IPC分类号： C12N15/31
CPC分类号： C12N15/102 , A61K39/04 , A61K2039/522 , C12R1/325
摘要： Particular aspects provide efficient allelic exchange methods to generate directed mutations within genes of slow-growing stains of mycobacteria (e.g., Mycobacterium avium subsp. paratuberculosis (Map), Map10 or GFP-expressing Map K-10) using a phage-delivery system, and demonstrate high efficiency allelic exchange. Additional exemplary aspects provide non-naturally occurring slow-growing strains of mycobacteria (e.g., Map, M. bovis, M. tuberculosis) having at least one gene deletion (e.g., pknG, relA, lsr2, panC, panD, proC, trpD, sapM (MAP3432), lysA_1, leuD, and leuC, and deletion mutants at the orthologous loci of two known virulence genes in pathogenic mycobacteria (relA and pknG) and one gene related to colony morphology and biofilm formation in fast growing mycobacteria (lsr2) were made. Further aspects provide novel vaccines comprising such deletion mutants, or portions thereof, and methods for making said vaccines. Yet further aspects provide methods for protecting a mammal from virulent Map, M. bovis, or M. tuberculosis, comprising treating the mammal with the inventive vaccines.
摘要翻译：具体方面提供了使用噬菌体递送系统在缓慢生长的分枝杆菌染色体（例如鸟分枝杆菌副结核亚种（Map），Map10或GFP表达Map K-10）的基因内产生定向突变的有效等位基因交换方法，以及展示高效率的等位基因交换。其他示例性方面提供了具有至少一个基因缺失的非天然存在的慢性分枝杆菌菌株（例如，Map，M.bovis，结核分枝杆菌）（例如pknG，relA，lsr2，panC，panD，proC，trpD，在致病性分枝杆菌中两种已知毒力基因（relA和pknG）的直系同源基因座上的sapM（MAP3432），lysA_1，leuD和leuC以及与快速生长的分枝杆菌（lsr2）中的菌落形态和生物膜形成有关的一种基因的缺失突变体分别是进一步的方面提供了用于保护哺乳动物免受毒性Map，牛分枝杆菌或结核分枝杆菌的方法，所述方法包括用本发明的疫苗。

2. 发明专利

MX2010000427A MUTAGENESIS DE INTERCAMBIO ALELICO EN MAP. 未知
公开(公告)号：MX2010000427A
公开(公告)日：2010-08-18
申请号：MX2010000427
申请日：2008-07-14
申请人： UNIV WASHINGTON STATE
发明人： DAHLHEIMER JOHN , DAVIS WILLIAM C , HAMILTON MARY JO , PARK KUN TAEK
IPC分类号： C12N15/09 , C12N1/21
摘要： Aspectos particulares proporcionan métodos de intercambio alélico eficiente para generar mutaciones dirigidas dentro de genes de cepas de lento crecimiento de micobacterias (por ejemplo Mycobacterium avium subespecie paratuberculosis (Map), Map10 o Map K(10) que expresa GFP al usar un sistema de suministro de fagos, y demostrar intercambio alélico de alta eficiencia. Aspectos ejemplares adicionales proporcionan cepas de lento crecimiento que no se presentan naturalmente de micobacterias (por ejemplo, Map, M. bovis, M. tuberculosis) que tienen al menos una supresión de genes (por ejemplo, pknG, relA, lsr2, panC, panD, proC, trpD, sapM (MAP3432), lysA_I, leuD, y leuC, y se hicieron mutantes de supresión en los lugares ortólogos de dos genes de virulencia conocidos en micobacterias patogénicas (relA y pknG) y un gen relacionado con la morfología de colonias y formación de biopelículas en micobacterias de rápido crecimiento (lsr2). Aspectos adicionales proporcionan vacunas novedosas que comprenden tales mutantes de eliminación, o porciones de los mismos, y métodos para la elaboración de dichas vacunas. Aspectos todavía adicionales proporcionan métodos para proteger a un mamífero de Map, M. bovis o M. tuberculosis virulentos, que comprenden tratar al mamífero con las vacunas de la invención.

3. 发明专利

CA2692984A1 Allelic exchange mutagenesis in map. 未知
公开(公告)号：CA2692984A1
公开(公告)日：2009-01-15
申请号：CA2692984
申请日：2008-07-14
申请人： UNIV WASHINGTON STATE
发明人： DAVIS WILLIAM C , HAMILTON MARY JO , DAHL JOHN , PARK KUN TAEK
IPC分类号： C12N15/09 , C12N1/21
摘要： Particular aspects provide efficient allelic exchange methods to generate directed mutations within genes of slow-growing stains of mycobacteria (e.g., Mycobacterium avium subsp. paratuberculosis (Map), Map 10 or GFP-expressing Map K-10) using a phage-delivery system, and demonstrate high efficiency allelic exchange. Additional exemplary aspects provide non-naturally occurring slow-growing strains of mycobacteria (e.g., Map, M. bovis, M. tuberculosis) having at least one gene deletion (e.g., pknG, relA, lsr2, panC, panD, proC, trpD, sapM (MAP3432), lysA_1, leuD, and leuC, and deletion mutants at the orthologous loci of two known virulence genes in pathogenic mycobacteria (relA and pknG) and one gene related to colony morphology and biofilm formation in fast growing mycobacteria (lsr2) were made. Further aspects provide novel vaccines comprising such deletion mutants, or portions thereof, and methods for making said vaccines. Yet further aspects provide methods for protecting a mammal from virulent Map, M. bovis, or M. tuberculosis, comprising treating the mammal with the inventive vaccines.

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