Reversal of siRNA-mediated gene silencing in vivo
Nature biotechnology, 2018•nature.com
We report rapid, potent reversal of GalNAc-siRNA-mediated RNA interference (RNAi) activity
in vivo with short, synthetic, high-affinity oligonucleotides complementary to the siRNA guide
strand. We found that 9-mers with five locked nucleic acids (LNAs) have the highest potency
across several targets. Our modular, sequence-specific approach, named REVERSIR, may
enhance the therapeutic profile of any long-acting GalNAc–siRNA (short interfering RNA)
conjugate by enabling control of RNAi pharmacology.
in vivo with short, synthetic, high-affinity oligonucleotides complementary to the siRNA guide
strand. We found that 9-mers with five locked nucleic acids (LNAs) have the highest potency
across several targets. Our modular, sequence-specific approach, named REVERSIR, may
enhance the therapeutic profile of any long-acting GalNAc–siRNA (short interfering RNA)
conjugate by enabling control of RNAi pharmacology.
Abstract
We report rapid, potent reversal of GalNAc-siRNA-mediated RNA interference (RNAi) activity in vivo with short, synthetic, high-affinity oligonucleotides complementary to the siRNA guide strand. We found that 9-mers with five locked nucleic acids (LNAs) have the highest potency across several targets. Our modular, sequence-specific approach, named REVERSIR, may enhance the therapeutic profile of any long-acting GalNAc–siRNA (short interfering RNA) conjugate by enabling control of RNAi pharmacology.
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