Target gene abundance contributes to the efficiency of siRNA-mediated gene silencing.

Nucleic Acid Ther

1 Global Research Laboratory for RNAi Medicine, Department of Chemistry, Sungkyunkwan University, Suwon, Korea.

Published: June 2014

AI Article Synopsis

  • The activity of small interfering RNA (siRNA) in gene silencing is influenced by multiple factors, particularly the level of target mRNA expression.
  • Research shows that siRNAs targeting the KRT7 gene exhibit different silencing effectiveness depending on the cell line and the amount of KRT7 mRNA present.
  • The study highlights that higher levels of target mRNA make genes more susceptible to siRNA interference, offering insights that can inform RNAi experimental design and therapeutic applications.

Article Abstract

The gene-silencing activity of a small interfering RNA (siRNA) is determined by various factors. Considering that RNA interference (RNAi) is an unparalleled technology in both basic research and therapeutic applications, thorough understanding of the factors determining RNAi activity is critical. This report presents observations that siRNAs targeting KRT7 show cell-line-dependent activity, which correlates with the expression level of KRT7 mRNA. By modulating the target mRNA level, it was confirmed that highly expressed genes are more susceptible to siRNA-mediated gene silencing. Finally, several genes that show different expression levels in a cell-line dependent manner were tested, which verified the expression-level-dependent siRNA activities. These results strongly suggest that the abundance of target mRNA is a critical factor that determines the efficiency of the siRNA-mediated gene silencing in a given cellular context. This report should provide practical guidelines for designing RNAi experiments and for selecting targetable genes in RNAi therapeutics studies.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026300PMC
http://dx.doi.org/10.1089/nat.2013.0466DOI Listing

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