“This paper provides a comprehensive overview of the rapidly developing field of RNA interference (RNAi)...”

This paper provides a comprehensive overview of the rapidly developing field of RNA interference (RNAi) by examining both the basic biology of this gene regulation pathway and the development of tools that allow for the application of this phenomenon for gene silencing studies.

The discovery that small RNA molecules, termed short interfering (si)RNAs, are capable of silencing gene expression has fundamentally changed our understanding of the control of gene expression. These small RNA molecules are capable of guiding a ribonucleoprotein complex, the RNA-induced silencing complex (RISC), to the homologous mRNA, leading to mRNA degradation or the repression of translation. This highly conserved gene-silencing phenomenon, RNA interference, has been shown to play a key role in the regulation of development and the protection of an organism’s genome from invading pathogenic genetic elements. The discovery of this regulatory mechanism has not only proven to be an important biological process but has also allowed for the development of novel gene silencing techniques that have facilitated large scale gene function analysis, as well as opening the door for potential therapeutic gene silencing.

The use of small RNA molecules (siRNAs) offers a highly specific and effective method of silencing gene expression and holds a great deal of promise as a therapeutic agent, inhibiting potentially harmful gene products and pathogens.

Research in the lab was already at the cutting edge of RNA biology, including the study of RNA interference and its role in regulating gene expressions, when I became interested in applying the principles of RNAi for the therapeutic silencing of pathogenic genes, in particular, for the silencing of HIV expression and replication.