期刊
JOURNAL OF GENE MEDICINE
卷 11, 期 5, 页码 412-421出版社
WILEY
DOI: 10.1002/jgm.1314
关键词
gynaecophoral canal protein; pairing; RNA interference; Schistosoma japonicum; schistosomiasis
资金
- National Key Technology R&D Program of China [2006BAD06A09]
- National Basic Research Program of China [2007CB513108]
- 863 High-tech Project of China [2006AA10A2071]
- Shanghai Program for Raising Star of China [04QMX1462]
- National Natural Science Foundation of China [30270311]
Background Schistosomiasis causes liver and intestinal damage and can be very debilitating. The pairing of a male worm with a female worm residing in the gynaecophoral canal of male plays a critical role in the development of female parasite. Because the male specific gynaecophoral canal protein of Schistosoma japonicum (SjGCP) is found in significant quantities in the adult female worm after pairing, it could play an important role in parasite pairing. Methods in the present study, three small interfering (si)RNA duplexes targeting the SjGCP gene were designed, synthesized and the silencing effects were evaluated in vitro as well as in mice infected with S. japonicum in vivo. Results In vitro studies using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR revealed the reduction of SjGCP at the transcript level. Similarly, western blotting and immunofluorescence studies showed its reduction at the protein level after treatment of parasites with siRNAs. At a concentration of 200 nm, two siRNAs totally abolished the parasite pairing. To evaluate such a pairing inhibitory effect in vivo, mice infected with S. japonicum were treated with siRNA and both parasite pairing and burden were evaluated. In vivo tests confirmed the in vitro silencing effect of SjGCP siRNA and revealed that the systemic delivery of siRNA significantly inhibited early parasite pairing and the associated burden. Conclusions Our preliminary results demonstrated that the SjGCP plays an important role in pairing and subsequent development in S. japonicum, and its silencing might have potential as a therapeutic approach for controlling schistosomiasis. Copyright (C) 2009 John Wiley & Sons, Ltd.
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