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    • 21. 发明申请
    • IMPROVED COMBINATION BACTERIOLYTIC THERAPY FOR THE TREATMENT OF TUMORS
    • 改进的联合用于治疗肿瘤的细菌疗法
    • WO2005039492A9
    • 2005-06-02
    • PCT/US2004034625
    • 2004-10-21
    • UNIV JOHNS HOPKINSDANG LONGBETTEGOWDA CHETANKINZLER KENNETH WVOGELSTEIN BERT
    • DANG LONGBETTEGOWDA CHETANKINZLER KENNETH WVOGELSTEIN BERT
    • A01N63/00A61K20060101A61K
    • A61K35/742A61K31/337A61K31/427A61K45/06Y10S435/842A61K2300/00
    • Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sponzlated bacteria. Mechanistic studies showed that the microtubule destabilizers, but not the microtubule stabilizers, radically reduced blood flow to tumors, thereby enlarging the hypoxic niche in which spores could germinate. A single intravenous injection of spores plus selected microtubule-interacting agents was able to cause regressions of several tumors in the absence of excessive toxicity.
    • 目前用于治疗癌症的方法部分地由于药物不能影响肿瘤血管化程度差的区域而受到限制。 我们发现厌氧菌的孢子与微管相互作用的药物联合使用会导致肿瘤血管和血管腔的破坏。 发现两类微管抑制剂发挥显着不同的作用。 一些抑制微管合成的药物,如长春瑞滨,当与孢子结合使用时会引起快速,大量的出血性坏死。 相反,稳定微管的药物,如紫杉类多西紫杉醇,则导致缓慢的肿瘤消退,从而杀死大多数肿瘤细胞。 肿瘤灌注不足区域的剩余细胞可以被脊椎化细菌消灭。 机理研究表明,微管去稳定剂,但不是微管稳定剂,从根本上减少了血液流向肿瘤,从而扩大了孢子可能发芽的缺氧生态位。 单次静脉注射孢子加选定的微管相互作用剂能够在没有过度毒性的情况下引起几种肿瘤的消退。
    • 27. 发明公开
    • 합성 조절 sRNA를 이용한 클로스트리듐 속 미생물 유전자의 발현 조절 방법
    • 使用合成调节小RNA在黑质中调节基因表达的方法
    • KR1020150142305A
    • 2015-12-22
    • KR1020140070869
    • 2014-06-11
    • 한국과학기술원
    • 이상엽조창희유승민
    • C12N15/11C12P7/16C12R1/145
    • C12N15/11C12P7/16C12R1/145Y10S435/842
    • 본발명은원핵생물인클로스트리디아() 내에서합성조절 sRNA를이용한유전자발현을억제하는방법에관한것으로, 보다상세하게는 MicC sRNA 유래의 Hfq 결합부위(Hfq binding site) 및표적유전자 mRNA와상보적결합을형성하는영역을포함하는합성 sRNA 카세트플라스미드에대장균유래 Hfq 유전자를추가로삽입한후, 클로스트리듐속 미생물에도입하여유전자의발현을억제하는방법에관한것이다. 본발명에따른합성조절 sRNA를이용한클로스트리듐속 미생물유전자의발현억제방법은유전자결실과정없이효과적으로표적유전자발현을억제할수 있으므로, 클로스트리듐속 미생물에서다양한표적유전자의조합을동시다발적으로억제하여대사흐름을조절함에따라다양한유기산생산은물론, 대체에너지원으로사용가능한고효율의에탄올및 부탄올생산균주제작에매우유용하다.
    • 本发明涉及使用合成调节性小RNA(sRNA)抑制作为原核生物的梭菌中的基因表达的方法,更具体地,涉及通过将大肠杆菌来源的Hfq基因另外插入到基因表达的方法来抑制基因表达的方法 合成盒质粒包括形成MicC sRNA衍生的Hfq结合位点与靶基因的mRNA之间的互补结合的区域,然后将其引入梭菌中的微生物中。 根据本发明,使用合成调节性sRNA抑制梭菌中的微生物的基因表达的方法可以有效地抑制靶基因表达而无需基因缺失过程,以同时抑制梭菌中微生物中各种靶基因的组合 以调节代谢流以产生各种有机酸,并构建可用作替代能源的用于生产高效乙醇和丁醇的菌株。