Reversal of SiRNA-mediated Gene Silencing in Vivo

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2018 May 23

PMID 29786096

Citations 35

Authors

Ivan Zlatev

Adam Castoreno

Christopher R Brown

June Qin

Scott Waldron

Mark K Schlegel

Rohan Degaonkar

Svetlana Shulga-Morskaya

Huilei Xu

Swati Gupta

Shigeo Matsuda

Akin Akinc

Kallanthottathil G Rajeev

Muthiah Manoharan

Martin A Maier

Vasant Jadhav

Affiliations

Soon will be listed here.

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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