Reversal of siRNA-mediated gene silencing in vivo.

Zlatev, Ivan; Castoreno, Adam; Brown, Christopher R; Qin, June; Waldron, Scott; Schlegel, Mark K; Degaonkar, Rohan; Shulga-Morskaya, Svetlana et al. · Nat Biotechnol · 2018

basic_science · Level V

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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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