microRNA-132

Class

Anti-miR-132 oligonucleotide

MicroRNAs are small non-coding RNA molecules that regulate gene expression after a gene has been transcribed, by binding to messenger RNA and blocking translation into protein. MicroRNA-132 (miR-132) is one such regulator whose levels rise in heart tissue under mechanical or neurohormonal stress. Elevated miR-132 has been linked to pathological cardiac remodeling, the maladaptive thickening and stiffening of heart muscle seen in heart failure, largely by suppressing genes involved in calcium handling and autophagy, the cellular process that clears damaged components. Anti-miR-132 oligonucleotides are synthetic, chemically modified nucleic acid strands designed to bind miR-132 directly through complementary base pairing, sequestering it so it can no longer silence its target genes. This restores expression of the proteins miR-132 would otherwise suppress, with the aim of slowing or reversing remodeling in chronic heart failure and related cardiac stress states. Because a single microRNA typically regulates many genes as part of an interconnected network, targeting it can influence multiple downstream pathways simultaneously. This is both the appeal of the approach, offering broader pathway modulation than a single-protein drug, and a source of added biological complexity that must be carefully characterized.