Cypor-Cas9 RNP

Cypor-Cas9 RNP is a preclinical CRISPR-Cas9 ribonucleoprotein (RNP) complex designed to target and disrupt the gene encoding cytochrome P450 oxidoreductase (*Por* or *Cypor*). Cypor is an obligate electron donor for microsomal cytochrome P450 enzymes, which metabolize acetaminophen (APAP) into its hepatotoxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). By knocking out Cypor, edited hepatocytes become resistant to APAP-induced toxicity, allowing for selective in vivo expansion and liver repopulation with transplanted, gene-edited hepatocytes upon transient APAP administration. This therapy is being developed as a nonviral ex vivo cell-based gene editing strategy for inherited metabolic liver diseases, such as phenylketonuria (PKU). However, studies in homozygous familial hypercholesterolemia (HoFH) models indicated that Cypor disruption impairs cholesterol metabolism and clearance, suggesting that this specific selection strategy may not be suitable for all metabolic liver disorders.

Other names

Cypor-Cas9 ribonucleoproteinCypor-Cas-9 ribonucleoproteinCypor-Cas 9 ribonucleoproteinCypor-targeting CRISPR-Cas9 RNPCypor-targeting CRISPR-Cas9 ribonucleoproteinCypor-targeting Cas9 RNP