RNA interference-mediated simultaneous silencing of four genes using cross-shaped RNA

Mol Cells. 2013 Apr;35(4):320-6. doi: 10.1007/s10059-013-2316-7. Epub 2013 Apr 4.


The structural flexibility of RNA interference (RNAi)-triggering nucleic acids suggests that the design of unconventional RNAi trigger structures with novel features is possible. Here, we report a cross-shaped RNA duplex structure, termed quadruple interfering RNA (qiRNA), with multiple target gene silencing activity. qiRNA triggers the simultaneous down-regulation of four cellular target genes via an RNAi mechanism. In addition, qiRNA shows enhanced intracellular delivery and target gene silencing over conventional siRNA when complexed with jetPEI, a linear polyethyleneimine (PEI). We also show that the long antisense strand of qiRNA is incorporated intact into an RNA-induced silencing complex (RISC). This novel RNA scaffold further expands the repertoire of RNAi-triggering molecular structures and could be used in the development of therapeutics for various diseases including viral infections and cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Silencing*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Nucleic Acid Conformation
  • RNA / chemistry*
  • RNA / genetics*
  • RNA Interference*
  • Transfection


  • RNA