RNA interference (RNAi) inhibits growth of Plasmodium falciparum

作者: Louisa McRobert , Glenn A McConkey

DOI: 10.1016/S0166-6851(01)00429-7

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摘要: RNA interference (RNAi) causes degradation of targeted endogenous in many diverse organisms. Erythrocyte-infecting stages the malaria parasite Plasmodium falciparum were treated with double-stranded (dsRNA) encoding a segment gene dihydroorotate dehydrogenase (DHODH). DHODH is an enzyme pyrimidine biosynthesis, essential for growth. A decrease growth (P<0.0005) correlated levels mRNA. Control treatments single-stranded RNA, dsRNA circumsporozoite protein (a stage-specific not expressed asexual blood stage) and from related organism Toxoplasma gondii did inhibit As test RNAi assay, parasites chorismate synthase (CS), thought to be involved folate synthesis, examine requirement this Growth decreased (P<0.001) though less markedly than by DHODH. These results demonstrate utility assay assessing requirements products, their potential as chemotherapeutic targets.

参考文章(33)
Sayda M. Elbashir, Jens Harborth, Winfried Lendeckel, Abdullah Yalcin, Klaus Weber, Thomas Tuschl, Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells Nature. ,vol. 411, pp. 494- 498 ,(2001) , 10.1038/35078107
Maria E. Fichera, David S. Roos, A plastid organelle as a drug target in apicomplexan parasites Nature. ,vol. 390, pp. 407- 409 ,(1997) , 10.1038/37132
Andrew Fire, SiQun Xu, Mary K. Montgomery, Steven A. Kostas, Samuel E. Driver, Craig C. Mello, Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans Nature. ,vol. 391, pp. 806- 811 ,(1998) , 10.1038/35888
Fiona Roberts, Craig W Roberts, Jennifer J Johnson, Dennis E Kyle, Tino Krell, John R Coggins, Graham H Coombs, Wilbur K Milhous, Saul Tzipori, David JP Ferguson, Debopam Chakrabarti, Rima McLeod, None, Evidence for the shikimate pathway in apicomplexan parasites Nature. ,vol. 393, pp. 801- 805 ,(1998) , 10.1038/31723
S. Bowman, D. Lawson, D. Basham, D Brown, T. Chillingworth, C. M. Churcher, A. Craig, R. M. Davies, K. Devlin, T. Feltwell, S. Gentles, R. Gwilliam, N. Hamlin, D. Harris, S. Holroyd, T. Hornsby, P. Horrocks, K. Jagels, B. Jassal, S. Kyes, J. McLean, S. Moule, K. Mungall, L. Murphy, K. Oliver, M. A. Quail, M.-A. Rajandream, S. Rutter, J. Skelton, R. Squares, S. Squares, J. E. Sulston, S. Whitehead, J. R. Woodward, C. Newbold, B. G. Barrell, The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum Nature. ,vol. 400, pp. 532- 538 ,(1999) , 10.1038/22964
Julia M. Bosher, Michel Labouesse, RNA interference: genetic wand and genetic watchdog Nature Cell Biology. ,vol. 2, ,(2000) , 10.1038/35000102
Andrew Fire, RNA-triggered gene silencing Trends in Genetics. ,vol. 15, pp. 358- 363 ,(1999) , 10.1016/S0168-9525(99)01818-1
G. A. McConkey, I. Ittarat, S. R. Meshnick, T. F. McCutchan, Auxotrophs of Plasmodium falciparum dependent on p-aminobenzoic acid for growth. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 91, pp. 4244- 4248 ,(1994) , 10.1073/PNAS.91.10.4244
Y. Wu, L. A. Kirkman, T. E. Wellems, Transformation of Plasmodium falciparum malaria parasites by homologous integration of plasmids that confer resistance to pyrimethamine Proceedings of the National Academy of Sciences of the United States of America. ,vol. 93, pp. 1130- 1134 ,(1996) , 10.1073/PNAS.93.3.1130