A dual-specific CRISPR-Cas nanosystem for precision therapeutic editing of liver disorders

The most common liver disorders, such as acute liver injury and liver fibrosis, can induce acute or chronic inflammatory responses, which in turn gradually promote the development and progression of the disorder. 1 To date, limited therapeutic options are available for the treatment of these chronic or acute liver disorders. Recently, clustered, regularly interspaced, short palindromic repeat (CRISPR)-associated (CRISPR-Cas) systems have been harnessed as a therapeutic tool for treating genetic and non-genetic liver disorders. 2 , 3 However, in vivo delivery of either Cas9-based genome editor or CasRx-based RNA editor by viral or non-viral vectors inevitably suffers from non-specific distribution upon the intravenous administration, leading to the accumulation in non-targeted organs and tissues. As a result, the unwanted editing may cause genotoxicity and serious side effects that are difficult to predict.