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. 2018 Jul;36(6):509-511.
doi: 10.1038/nbt.4136. Epub 2018 May 14.

Reversal of siRNA-mediated Gene Silencing in Vivo


Reversal of siRNA-mediated Gene Silencing in Vivo

Ivan Zlatev et al. Nat Biotechnol. .


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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