CRISPR/Cas genome editing: Targeting hepatic diseases

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system is a state-of-the-art genome editing technology, utilizing single stranded RNA-guided DNA nucleases to form double strand breaks in DNA. With the help of cell repair machinery, gene insertions/deletions (indels) are introduced and loss-offunction mutations are generated. Liver is selected to be the target organ of the CRISPR/Cas system therapy for its principalship in intermediary metabolic reactions, immune privilege, natural tropism by vectors and less potentials for deleterious complications. Liver-targeted gene editing is a hot field due to its promise in hereditary diseases caused by single- gene abnormalities. In this chapter, pre-clinical experiments using CRISPR/Cas systems to treat metabolic disorders (including haemophilia B, familial hypercholesterolemia, hereditary tyrosinemia type I, etc.), neoplastic diseases and viral infection are discussed. Nonetheless, CRISPR/Cas system as the most widely used gene editing tool, still has some drawbacks such as its transduction efficiency, specificity, safetyimmunogenecity and safety-genotoxicity.