Effective and Accurate Gene Silencing by a Recombinant AAV-Compatible MicroRNA Scaffold

Abstract

Efficient and specific gene silencing is a challenge for rAAV-mediated RNAi. Short hairpin-induced vector genomic truncations raised concerns for clinical transition. Xie and colleagues report that an artificial miRNA scaffold derived from mouse miR-33 ensures rAAV genomic integrity and reduces off-targeting 10-fold, while maintaining effective target gene repression in vivo in mice.