Research press release


Nature Biotechnology

RNA interference targets the placenta



Anastasia Khvorovaたちは、低分子干渉RNA(siRNA)を静脈注射や皮下注射によって胎盤に送達し、sFlt1の合成を阻害した。この処置により、妊娠中のマウスと妊娠高血圧腎症のヒヒモデルで血中のsFlt1濃度が低下した。今回の方法は、これまでの研究とは対照的に、1回の注射だけで、生産場所である胎盤においてsFlt1を抑制した。これまでsiRNA療法の開発は主に肝臓に的を絞って行われてきたが、胎盤を標的にできることで、治療に新たな道が開けるかもしれない。

RNA interference, an emerging therapeutic strategy for silencing disease-causing genes, reduces expression in the mouse and baboon placenta of a gene responsible for preeclampsia, reports a study published online this week in Nature Biotechnology. Further animal studies of efficacy and safety are needed before this approach could be considered for clinical trials in women with preeclampsia, a disorder of high blood pressure that affects 5-10 percent of pregnancies.

Preeclampsia symptoms arise from abnormally high circulating levels of the protein sFLT1, which is produced in the placenta and secreted into the blood. sFLT1 is considered a promising therapeutic target, and several approaches to lower its activity have been tested.

Anastasia Khvorova and colleagues block sFlt1 synthesis in the placenta using small interfering RNA (siRNA) delivered intravenously or subcutaneously. The treatment reduces circulating levels of sFlt 1 in pregnant mice and in a baboon model of preeclampsia. In contrast to previous work, the approach is demonstrated with only a single injection and suppresses sFlt1 right where it is produced, in the placenta. The development of siRNA therapies has been largely focused on the liver, and the ability to target the placenta may open new therapeutic avenues.

doi: 10.1038/nbt.4297

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