Targeted drugs that recognize biological molecular structures, as well as small nucleic acid drugs and gene-editing medicines that identify nucleic acid sequences, often face the challenge of interspecies differences in targets between humans and animals. This can make it impossible to evaluate human drugs in animal models. Humanized liver mice, which are established by transplanting primary human hepatocytes into mice with damaged livers, replacing mouse hepatocytes with humans to form a chimeric liver, make it possible to evaluate human liver-targeted drugs in mouse models.

Hu-URG^® is a humanized liver mouse model established by Vitalstar Company, where the replacement rate of human hepatocytes can reach up to 90%. These human liver cells maintain normal gene expression profiles within the mouse body, retaining normal functions. In this model, the targets unique to human hepatocyte not only exist  but also are parts of a fully functional regulatory network. There is no incompatibility between the humanized target genes and the upstream and downstream regulatory mechanisms, making it highly suitable for the screening and evaluation of hepatocyte-targeted drugs.

1. Hu-URG^®

Figure 1. The concentrations of several human blood lipid-related proteins and compliment-related proteins in serum of Hu-URG^® mice

High levels of proteins secreted by human hepatocytes, such as PCSK9, ApoC, Apo(a), Angptl3, and C1-INH, can be detected in the blood of Hu-URG® mice. These proteins have recently become hot targets for drug development for regulating blood lipids and intervening complement activity.

Figure 2. Blood lipid profile in Hu-URG^®and URG mice

Liver plays a crucial role in lipid metabolism. There is a significant difference in the blood lipid composition between mice and humans. Mice have lower levels of low-density lipoprotein cholesterol (LDL-C) and higher levels of high-density lipoprotein cholesterol (HDL-C), whereas humans have the opposite profile. After the humanization of liver, this difference is reversed, making the blood lipid composition more similar to that of humans.