Alex Deiters

North Carolina State University
Discovery and application of small molecule modifiers of microRNA function

MicroRNAs are single stranded ribonucleic acid (RNA) molecules of approximately 20 nucleotides that regulate gene expression by specific binding to the 3’ untranslated region of target messenger RNAs, leading to the downregulation of gene expression. It has been estimated that microRNAs are involved in the regulation of up to 30% of all genes in humans. The microRNA miR-122 is the most abundant miRNA in the liver and is necessary for the translation and replication of the hepatitis C virus (HCV). At the Teva Symposium, small molecules capable of specifically inhibiting the activity of miR-122 were presented.

These compounds constitute new tools to elucidate the involvement of miR-122 in HCV infection and could potentially be developed into fundamentally new antiviral therapeutic agents. Current studies that involve structure-activity relationship investigations to understand the molecular requirements for the miR-122 inhibitory activity were discussed and steps toward the elucidation of the precise mode of action of the discovered inhibitors were outlined. In addition, initial investigations of the small molecules’ antiviral activity showed the ability to greatly reduce HCV levels in human liver cells.

Discussions with Teva scientists at the symposium provided important insight into additional future directions of the presented inhibition of miR-122 by small molecules.