Antisense Inhibition of Fas Expression for Treatment of Liver Disease

Fas (CD95) belongs to tumor necrosis factor receptor (TNFR) family. Fas is constitutively expressed in liver. While its role in controlling homeostasis of cellularity in normal liver remains to be elucidated, many studies have demonstrated that Fas expression in liver is up-regulated under certain inflammatory conditions. In a number of clinical reports, liver damage appears correlated with Fas expression and apoptosis during progression of several hepatic diseases. Therefore, Fas likely represents an attractive therapeutic target to control excessive or abnormal apoptosis in liver. Antisense oligonucleotides have been broadly applied in specific inhibition of gene expression in many organs, including liver. Using antisense oligonucleotide inhibiting Fas, it has been demonstrated an effective protection of animals from liver apoptotic injury and fulminant death.