公开(公告)号：WO2015118541A1

公开(公告)日：2015-08-13

申请号：PCT/IL2015/050137

申请日：2015-02-05

申请人： GAVISH-GALILEE BIO APPLICATIONS LTD

发明人： KATZ, Chen ,  PITCOVSKI, Jacob ,  AIZENSHTEIN, Elina ,  NOACH, Caroline ,  FINGER, Avner

IPC分类号： C12N15/09 ,  C12N15/31 ,  C12N15/70 ,  C12N15/71 ,  C12N15/72 ,  C12N15/74 ,  C12N1/21

CPC分类号： A61K39/0258 ,  A61K39/0275 ,  A61K2039/5252 ,  A61K2039/5254 ,  A61K2039/552 ,  C07K14/245 ,  C12N1/36 ,  C12N9/16 ,  C12N15/70 ,  C12N15/74 ,  Y02A50/474 ,  Y02A50/482

摘要： The present invention provides a DNA molecule comprising a nucleic acid sequence including at least one pair of a first and a second differentially controlled transcription units, wherein the first transcription unit includes a first promoter operably linked to a first gene encoding a cytotoxic gene product, the second transcription unit includes a second promoter that is different from the first promoter and is operably linked to a second gene encoding a gene product neutralizing said cytotoxic gene product, at least one of said first and said second promoter is a regulated promoter responsive to a predetermined condition, and said DNA molecule is designed such that under said predetermined condition the amount of said neutralizing gene product is not sufficient to neutralize the cytotoxic effect of the cytotoxic gene product. The present invention further provides conditionally inactivated or attenuated bacteria comprising the DNA molecule of the invention, and vaccines comprising them.

摘要翻译： 本发明提供了一种DNA分子，其包含包含至少一对第一和第二差异控制的转录单位的核酸序列，其中所述第一转录单位包括与编码细胞毒性基因产物的第一基因可操作地连接的第一启动子， 第二转录单元包括不同于第一启动子的第二启动子，并且可操作地连接到编码中和所述细胞毒性基因产物的基因产物的第二基因，所述第一和所述第二启动子中的至少一个是响应于预定的 条件，并且所述DNA分子被设计成使得在所述预定条件下，所述中和基因产物的量不足以中和细胞毒性基因产物的细胞毒性作用。 本发明还提供了包含本发明的DNA分子的条件灭活或减毒的细菌，以及包含它们的疫苗。