%A Sheng,Peike %A Flood,Krystal A. %A Xie,Mingyi %D 2020 %J Frontiers in Bioengineering and Biotechnology %C %F %G English %K RNA Interference,Short hairpin RNA,Argonaute,dicer,microRNA,m7G-capped pre-miRNA,transcription start site miRNA %Q %R 10.3389/fbioe.2020.00940 %W %L %M %P %7 %8 2020-August-07 %9 Brief Research Report %# %! shRNA for single siRNA expression %* %< %T Short Hairpin RNAs for Strand-Specific Small Interfering RNA Production %U https://www.frontiersin.org/articles/10.3389/fbioe.2020.00940 %V 8 %0 JOURNAL ARTICLE %@ 2296-4185 %X RNA interference (RNAi) is an effective mechanism for inhibiting gene expression at the post-transcriptional level. Expression of a messenger RNA (mRNA) can be inhibited by a ∼22-nucleotide (nt) small interfering (si)RNA with the corresponding reverse complementary sequence. Typically, a duplex of siRNA, composed of the desired siRNA and a passenger strand, is processed from a short hairpin RNA (shRNA) precursor by Dicer. Subsequently, one strand of the siRNA duplex is associated with Argonaute (Ago) protein for RNAi. Although RNAi is widely used, the off-target effect induced by the passenger strand remains a potential problem. Here, based on current understanding of endogenous precursor microRNA (pre-miRNA) hairpins, called Ago-shRNA and m7G-capped pre-miRNA, we discuss the principles of shRNA designs that produce a single siRNA from one strand of the hairpin.