Correlation between hammerhead ribozyme-mediated eggshell protein gene cleavage and reproduction inhibition of Schistosoma japonicum.

Correlation between hammerhead ribozyme-mediated eggshell protein gene cleavage and reproduction inhibition of Schistosoma japonicum.
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DOI:
10.3892/mmr.2012.752
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发表时间:
2012-04
影响因子:
3.4
通讯作者:
Xiao J
Xiao J
中科院分区:
医学4区
文献类型:
--
作者:
Liang Y;Zhou Y;Yin W;Li Y;Yang Q;Gao Y;Zhang Y;Yang Y;Peng L;Xiao J

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日本血吸虫(S.是一种极其有害的病原体,它感染人类并引起严重的公共卫生问题。迄今为止,还没有针对这种病原体的有效治疗药物。本研究设计并构建了三种针对沙门氏菌蛋壳蛋白基因的锤头状核酶。日本血吸虫(SjESG)。使用切割实验测定这三种核酶的切割活性。体外切割结果表明,在所合成的3种核酶(Rz 1、Rz 2和Rz 3)中,Rz 1和Rz 3能有效地切割靶RNA。然而,Rz 2不能可检测地切割其靶RNA。这三种核酶对S.日本血吸虫在小鼠体内的作用。与阴性对照相比,Rz 1和Rz 3处理导致小鼠IFN-γ水平升高,但IL-4水平降低。Rz 2对IFN-γ和IL-4水平的影响程度与载体对照所引起的相似。此外,Rz 1和Rz 3比Rz 2和载体对照更广泛地减少了小鼠肝脏中蠕虫和卵的数量。总之,这些结果表明Rz 1和Rz 3的体外切割能力与它们在S.山茱萸
Schistosoma japonicum (S. japonicum) is an extremely harmful pathogen, which infects humans and causes severe public health problems. To date, no effective therapeutic drugs for this pathogen are available. In this study, we designed and constructed three hammerhead ribozymes targeting the eggshell protein gene of S. japonicum (SjESG). The cleavage activities of these three ribozymes were determined using cleavage experiments. The in vitro cleavage results showed that among the three synthesized ribozymes (Rz1, Rz2 and Rz3), Rz1 and Rz3 cleaved their target RNAs effectively. However, Rz2 did not cleave its target RNA detectably. The putative therapeutic roles of these three ribozymes to inhibit the reproduction of S. japonicum in mice were studied in vivo. Compared with the negative controls, Rz1 and Rz3 treatments resulted in increased levels of IFN-γ but decreased levels of IL-4 in mice. Rz2 affected levels of IFN-γ and IL-4 to degrees similar with those caused by the vector controls. In addition, Rz1 and Rz3 reduced the amounts of adult worms and eggs in the livers of mice more extensively than Rz2 and the vector controls. Altogether, these results suggest a correlation between the in vitro cleavage abilities of Rz1 and Rz3 and their roles in reproduction inhibition of S. japonicum.
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