PLN antisense oligonucleotide

PLN antisense oligonucleotide (PLN-ASO) is an RNA-targeted therapeutic platform designed to downregulate the expression of phospholamban (PLN), a key sarcoplasmic reticulum membrane protein that regulates calcium cycling in cardiomyocytes. Under normal conditions, unphosphorylated PLN inhibits the sarco/endoplasmic reticulum calcium ATPase 2a (SERCA2a) pump, which transports calcium from the cytosol back into the sarcoplasmic reticulum during cardiac relaxation. Pathogenic mutations in the PLN gene, such as the Dutch founder mutation p.Arg14del (R14del), lead to abnormal PLN protein aggregation, calcium dysregulation, and severe dilated or arrhythmogenic cardiomyopathy. By targeting PLN mRNA for degradation, PLN-ASOs reduce PLN expression, restore SERCA2a activity, resolve toxic protein aggregates, and improve cardiac contractility and calcium handling. Preclinical development of PLN-ASOs has been conducted by Ionis Pharmaceuticals in collaboration with AstraZeneca and the University Medical Center Groningen.

Other names

PLN ASOPLN-ASOphospholamban ASOphospholamban antisense oligonucleotide