PCSK9 epigenetic editor

The PCSK9 epigenetic editor is an investigational genetic medicine developed by nChroma Bio (formerly Chroma Medicine) for the treatment of cardiometabolic diseases, specifically hypercholesterolemia. The therapeutic system consists of three primary components: a single mRNA encoding an epigenetic editor (EE) fusion protein, guide RNAs (gRNAs) targeting the human PCSK9 promoter region, and a lipid nanoparticle (LNP) delivery system optimized for hepatocyte uptake. Unlike traditional gene editing technologies that create double-strand breaks in DNA, this platform utilizes epigenetic editing to induce site-specific DNA methylation at the PCSK9 locus. This targeted methylation leads to durable transcriptional silencing of the PCSK9 gene, resulting in a significant reduction of circulating PCSK9 protein and low-density lipoprotein (LDL) cholesterol levels. Preclinical studies in non-human primates have demonstrated that a single administration can potently and durably decrease circulating PCSK9 levels by approximately 90%, with effects maintained for at least one year.

Other names

nChroma PCSK9 programChroma Medicine PCSK9 program