Selection and optimization of asymmetric siRNA targeting the human c-MET gene

Mol Cells. 2011 Dec;32(6):543-8. doi: 10.1007/s10059-011-0160-1. Epub 2011 Nov 3.


The silencing of specific oncogenes via RNA interference (RNAi) holds great promise for the future of cancer therapy. RNAi is commonly carried out using small interfering RNA (siRNA) composed of a 19 bp duplex region with a 2-nucleotide overhang at each 3' end. This classical siRNA structure, however, can trigger non-specific effects, which has hampered the development of specific and safe RNAi therapeutics. Previously, we developed a novel siRNA structure, called asymmetric shorter-duplex siRNA (asiRNA), which did not cause the non-specific effects triggered by conventional siRNA, such as off-target gene silencing mediated by the sense strand. In this study, we first screened potent asiRNA molecules targeting the human c-MET gene, a promising anticancer target. Next, the activity of a selected asiRNA was further optimized by introducing a locked nucleic acid (LNA) to maximize the gene silencing potency. The optimized asiRNA targeted to c-MET may have potential as a specific and safe anticancer RNAi therapeutic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Base Sequence
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression / drug effects
  • Gene Knockdown Techniques
  • Genes, Reporter
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Luciferases / biosynthesis
  • Luciferases / genetics
  • Oligonucleotides / pharmacology*
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • RNA Interference
  • RNA, Small Interfering / pharmacology*


  • Antineoplastic Agents
  • Oligonucleotides
  • RNA, Small Interfering
  • locked nucleic acid
  • Luciferases
  • Proto-Oncogene Proteins c-met