Precision RNAi using synthetic shRNAmir target sites.

Hoffmann, Thomas; Hörmann, Alexandra; Corcokovic, Maja; Zmajkovic, Jakub; Hinterndorfer, Matthias; Salkanovic, Jasko; Spreitzer, Fiona; Köferle, Anna et al. · Elife · 2023

basic_science · Level V

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Abstract

Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient and inducible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. ARTi establishes a scalable loss-of-function tool with full control over on- and off-target effects.

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