Novel hydrophobically modified asymmetric RNAi compounds (sd-rxRNA) demonstrate robust efficacy in the eye.
作者： Michael Byrne , Radouil Tzekov , Yi Wang , Amanda Rodgers , James Cardia
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摘要: Abstract Purpose: The major challenges of developing an RNAi therapeutic include efficient delivery to and entry into the cell type interest. Conventional (“naked” chemically stabilized) small interfering RNAs (siRNAs) have been used in eye past but they demonstrated limited clinical efficacy. Here we investigated a recently developed class small, hydrophobic, asymmetric compounds. These compounds, termed “self-delivering rxRNAs” (sd-rxRNA®), are extensively modified, duplex region <15 base pairs, contain fully phosphorothioated single-stranded tail, readily enter cells tissues without requirement for vehicle. Methods: We compared sd-rxRNA compounds with stabilized siRNAs vitro (in ARPE-19 cells) vivo (intravitreal injection mouse rabbit eyes). Specifically, retinal uptake, distribution, efficacy, preliminary safety sd-rxRNAs. Results: Treatment sd-rxRNAs resulted uniform cellular uptake ...
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