Engineered exosomes for future gene-editing therapy.

The RNA-guided clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated nuclease protein 9 (Cas9)-based technology is an advanced and popular gene-editing technology, which has shown great potential in treating genetic disorders in both animal models and even in clinical trials.1, 2 Many transportation strategies are available for delivery of the CRISPR-Cas9 system, among which Cas9 ribonucleoprotein (RNP) delivery has some competitive advantages over other options, such as faster editing onset speed with a reduced immune response and lower off-target activity.3, 4 However, the low in vivo delivery efficiency and poor tissue specificity of RNP delivery have limited further clinical applications.5 Writing in Science Advances, Wan et al.6 reported a previously-unidentified genome editing delivery system, named exosomeRNP which transported RNPs within exosomes extracted from hepatic stellate cells via electroporation. The exosomeRNP exhibited effective intracellular and intercellular delivery and accumulation of RNPs to hepatocytes in vitro and in vivo, resulting in significant therapeutic effects in several hepatic diseases. The system was tested in mouse models of acute liver injury, chronic liver fibrosis, and hepatocellular carcinoma by targeting p53 upregulated modulator of apoptosis, cyclin-E1, and K(lysine) acetyltransferase-5, respectively, providing a potential strategy for high-efficiency, precise and tissue-specific gene editing in liver diseases.