Therapeutic Strategy

MicroRNAs

MicroRNAs represent the next wave of breakthrough therapies for human disease. They are small non-coding RNAs that post-transcriptionally regulate networks of target gene expression. Encoded in the genome, microRNAs are initially synthesized as a longer primary RNA transcript, then processed by a series of nucleases into the ~19-23 nucleotide mature microRNA that is loaded into the RNA-induced silencing protein complex (RISC). The microRNA in RISC interacts with mRNA through complementary base pairing of the first 6-8 nucleotides of the microRNA, the “seed”, resulting in post-transcriptional inhibition of gene expression. Through simultaneous regulation of many target genes, microRNAs can modulate disease pathways (one-hit, multiple targets concept).

MicroRNAs (miRNAs) play important roles in the pathogenesis of many diseases including cancers, cancer, inflammation, neurodegeneration, atherosclerosis, cardiovascular, and metabolic disorders. Both microRNA antagonists (antagomirs) and agonists (agomirs or mimics) are currently in clinical development for a number of therapeutic indications. 

miRNAs are attractive drug candidates because the simultaneous modulation of many target genes by a single miRNA may provide effective therapies of complex diseases like obesity, diabetes mellitus and NAFLD/NASH.  We believe that inducing “browning” of subcutaneous WAT with microRNA analogs is a promising strategy for treating human obesity and related cardiometabolic disorders.