Small RNA Therapeutics
Introduction | History | Small RNA Therapeutics
The discovery of RNA interference (RNAi) has resulted in the development of a broad new class of targeted therapeutics called “short interfering RNAs” (siRNAs). siRNAs have the capacity to efficiently and specifically “knock down” the expression of individual genes and consequent gene products responsible for a number of diseases. More than 10 new companies have been formed and more than 20 existing companies have instituted programs in the last few years to develop and commercialize siRNA-based therapeutics.
miRNAs are the naturally occurring counterparts of siRNAs. miRNAs are expressed from genes as small RNA molecules that regulate global gene expression to facilitate the ordered development and maintenance of cells, tissues, and humans. The growing awareness of the importance of miRNAs has generated intense activity in the biomedical research community. miRNAs have been described as “biological dark matter,” a reference to their central importance in cellular regulation despite their very recent discovery. We believe that miRNAs are the next breakout class of therapeutic molecules following closely behind siRNA, and that miRNAs will have significant advantages over siRNAs in many applications.
The mis-regulation of certain miRNAs appears to contribute to the development and spread of cancer. Several groups, including scientists at Mirna Therapeutics, have shown that restoring mis-regulated miRNAs to their normal levels can reduce or even eliminate the growth of tumors in animal models of cancer. Since miRNAs are naturally occurring molecules, there are likely distinct advantages in applying miRNAs as therapeutic agents. miRNAs benefit from a billion years of evolutionary “fine tuning” of their function. Thus, sequence-specific “off target” effects should not be an issue with miRNAs. In addition, miRNAs have evolved to modulate the expression of groups of genes, driving both up and down regulation, with the result that complex cell functions can be precisely modulated. Researchers at Mirna have validated the concept of “miRNA Replacement Therapy” which involves introducing synthetic miRNAs or miRNA mimetics into diseased tissues in an effort to restore normal proliferation, apoptosis, cell cycle, and other cellular functions that have been affected by down-regulation of one or more miRNAs. In many cases, reactivation of these miRNA-regulated pathways leads to a significant therapeutic response.