Schistosoma mansoni: evaluation of an RNAi-based treatment targeting HGPRTase gene.
Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) is an essential gene of the parasite Schistosoma mansoni and it is well conserved in its hosts (mouse and human) at the protein but not at the RNA level. This feature prompted us to assess RNA interference (RNAi) to combat schistosomiasis. Small interfering RNAs (siRNAs) were produced against HGPRTase, injected in infected mice and the number of worms was counted six days after injection. The total number of parasites was reduced by approximately 27% after treatment. RT-PCR analyzes showed a significant reduction in parasite target mRNA but not in host's homologue. The use of low doses of molecules did not oversaturate si- or miRNA pathways as mice survival rates were not affected by siRNAs. This is the first successful in vivo demonstration of a RNAi-based treatment against schistosomiasis. We believe that improvements in molecule delivery and an increase on siRNA dose could rapidly eliminate parasite.
Pereira
T C
TC
Departamento de Genética Médica, Universidade Estadual de Campinas, Cidade Universitária Zeferino Vaz, FCM, Unicamp-Campinas, São Paulo, Brazil 13084-971.
Pascoal
V D B
VD
Marchesini
R B
RB
Maia
I G
IG
Magalhães
L A
LA
Zanotti-Magalhães
E M
EM
Lopes-Cendes
I
I
D000818:Animals; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007275:Injections, Intravenous; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012550:Schistosoma mansoni / Q000201:enzymology / Q000235:genetics*; D012555:Schistosomiasis mansoni / Q000469:parasitology / Q000628:therapy*; D013045:Species Specificity
D034741:RNA, Small Interfering; D007041:Hypoxanthine Phosphoribosyltransferase