CBE-MG34-1

CBE-MG34-1 is an experimental cytosine base editor (CBE) designed for the permanent knockdown of the *PCSK9* (Proprotein Convertase Subtilisin/Kexin Type 9) gene to treat hypercholesterolemia. Developed as a research lead, it utilizes a CRISPR-Cas9 nickase fused to a cytidine deaminase (such as APOBEC1) and a uracil glycosylase inhibitor (UGI). The system is guided by the MG34 single-guide RNA (sgRNA) to a specific sequence within the *PCSK9* gene, where it facilitates a precise cytosine-to-thymine (C-to-T) transition. This mutation typically disrupts a splice site or introduces a premature stop codon, leading to the loss of PCSK9 protein expression. Reduced PCSK9 levels result in a higher density of LDL receptors on the surface of liver cells, significantly lowering circulating low-density lipoprotein cholesterol (LDL-C). This construct demonstrated significant and durable efficacy in non-human primate models, serving as a critical proof-of-concept for in vivo base editing.

Other names

PCSK9-targeting cytosine base editorPCSK-9-targeting cytosine base editorPCSK 9-targeting cytosine base editor