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- W2143313350 abstract "Transfected siRNAs regulate numerous transcripts sharing limited complementarity to the RNA duplex. This unintended (“off-target”) silencing can hinder the use of RNAi to define gene function. Here we describe position-specific, sequence-independent chemical modifications that reduced silencing of partially complementary transcripts by all siRNAs tested. Silencing of perfectly matched targets was unaffected by these modifications. The chemical modification also reduced off-target phenotypes in growth inhibition studies. Key to the modification was 2′- O -methyl ribosyl substitution at position 2 in the guide strand, which reduced silencing of most off-target transcripts with complementarity to the seed region of the siRNA guide strand. The sharp position dependence of 2′- O -methyl ribosyl modification contrasts with the broader position dependence of base-pair substitutions within the seed region, suggesting a role for position 2 of the guide strand distinct from its effects on pairing to target transcripts." @default.
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- W2143313350 date "2006-05-08" @default.
- W2143313350 modified "2023-10-10" @default.
- W2143313350 title "Position-specific chemical modification of siRNAs reduces “off-target” transcript silencing" @default.
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- W2143313350 doi "https://doi.org/10.1261/rna.30706" @default.
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