What are microRNAs?

microRNAs are short (approximately 20-25 nucleotides long), single-stranded RNA molecules that regulate gene expression and play a vital role in influencing the pathways responsible for many disease processes, including cardiovascular disease and fibrosis. These RNAs are transcribed from genes; however, unlike messenger RNA they do not encode proteins.

microRNAs function by preventing the translation of microRNAs into proteins and/or by triggering degradation of these microRNAs. Studies have shown that microRNA gene regulation is often not a decisive on and off switch but a subtle function that fine-tunes cellular phenotypes that becomes more pronounced during stress or disease conditions. microRNAs were first discovered in 1993 and have since been found in nearly every biological system examined to date. They are highly conserved, demonstrating their importance to biological functions and cellular processes. According to the Sanger Institute, over 1000 microRNAs have been identified in humans.

microRNAs can be modulated with chemically synthesized oligonucleotides by either decreasing the activity (anti-miRs or inhibitors) or increasing the levels (pro-miRs or mimics) of expressed microRNAs. These modulators can then directly affect the protein expression of the specific microRNA’s targets. Typically, in laboratory settings, microRNA mimics are introduced as double stranded oligonucleotides and inhibitors are introduced as single strand oligonucleotides.

 

microRNA Platform

The understanding of how our genes contribute to the origin and progression of disease has been a foundation of modern medicine. While this knowledge has led to new drugs that selectively target products of individual disease genes, many disorders remain difficult to treat due to the fact that underlying disease processes are frequently driven by not one, but many genes – emphasizing the complex and central nature of gene regulation in disease.

Recently, scientists studying mechanisms of gene regulation have uncovered critical and unanticipated roles for a class of small ribonucleic acids (RNAs) known as microRNAs. These small, ancient RNAs have evolved to coordinately regulate distinct groups of genes that are central to many biological processes. Crucially, we now understand that large sets of complex, co-evolved processes can be effectively regulated through the manipulation of single microRNAs, a finding that has opened a path to a powerful new therapeutic paradigm.

We are exploiting the understanding of how microRNAs control biologic processes in health and disease to advance fundamentally new treatments for intractable diseases. We leverage our unique expertise in the fields of miRNA biology, the genetics of human disease, and oligonucleotide drug development to identify and select the best microRNA targets with the highest therapeutic potential, to apply best-in-class chemistries to create the safest and most effective compounds, and to build innovative approaches that will accelerate these discoveries to the clinic.

Our product-focused platform is directed at therapeutics targeting compelling microRNAs known to be critical for the development of complex diseases of high unmet need, including cancer, pathologic fibrosis and cardiovascular disease.