RNA interference (RNAi), an evolutionarily conserved sequence-specific post-transcriptional gene silencing mechanism, is triggered by
double-stranded RNA (dsRNA) that results in the degradation of homologous
mRNA or in the inhibition of mRNA translation. The naturally occurring triggers for the RNAi pathway are small regulatory RNAs, including small interfering RNAs (siRNAs), processed from longer dsRNAs by the
RNAse III enzyme Dicer, and
microRNAs (
miRNAs), generated in a regulated multistep process from endogenous primary transcripts (
pri-miRNA). These primary transcripts are capped, polyadenylated and spliced, thus resembling conventional mRNAs. It is estimated that
miRNAs regulate more than one third of all cellular mRNAs, and bioinformatic data indicate that each
miRNA can control hundreds of gene targets. Thus, there are likely to be few biological processes not regulated by
miRNAs. Although the
biological functions of
miRNAs are not completely revealed, there is growing evidence that
miRNA pathways are a new mechanism of gene regulation in both normal and diseased conditions. Recent evidence has shown that
miRNA mutations or aberrant expression patterns correlate with various diseases, such as
cancer,
viral infections, cardiovascular or
neurodegenerative diseases and indicates that
miRNAs can function as
tumor suppressors and oncogenes.
MiRNAs have not only emerged as a powerful tool for gene regulation studies but also for the development of novel drugs. Since they do not encode
proteins, they are not traditional therapeutic targets of small-molecule inhibitors and thus comprise a novel class of
therapeutics. This article will focus on the current progress in
drug discovery using the
miRNA strategy.