CRISPR/Cas9: at the cutting edge of hepatology

Abstract

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome engineering has revolutionised biomedical science and we are standing on the cusp of medical transformation. The therapeutic potential of this technology is tremendous, however, its translation to the clinic will be challenging. In this article, we review recent progress using this genome editing technology and explore its potential uses in studying and treating diseases of the liver. We discuss the development of new research tools and animal models as well as potential clinical applications, strategies and challenges.

Gene Therapy for Liver Cancers: Current Status from Basic to Clinics

“…Genome-editing technologies, including ZFN, TALEN, and Cas9 systems, have significantly broadened the ability to edit the genomic DNA in vitro, and even in vivo [29,32,177,178]. Delivery of in vitro-transcribed mRNA-mediated delivery of nucleases has various applications and future prospects of genome editing in research and clinical trials [179].…”

CRISPR–Cas-related technologies in basic and translational liver research

“…The most exciting translational use of CRISPR–Cas9 is the correction of mutations in genetic diseases (reviewed elsewhere 2 ). This approach has the potential to provide long-term therapy after a single treatment.…”

“…CRISPR genome editing tools are paving the way for new innovation in liver research 1,2 . The highly programmable nature of CRISPR is based on the Cas9 nuclease and guide RNA (sgRNA) complex that recognizes genomic sequences with a protospacer-adjacent motif (PAM, the DNA sequence immediately following the genomic sequence targeted by Cas9).…”

Using CRISPR/Cas9 to model human liver disease

“…Hence CRISPR is very efficient for destroying or inactivating genes (introducing mutations), with current efforts focused on increasing the efficiency of homology-directed repair (template-mediated repair), which would allow for the precise insertion of new sequences and could be used to correct genes. 11 These recent advances enable the rapid generation of embryonic and somatic modifications in animal models. Excellent reviews cover the development and application of CRISPR/ Cas9, [11][12][13][14][15] therefore, we will focus specifically on disease modelling for the liver.…”

“…11 These recent advances enable the rapid generation of embryonic and somatic modifications in animal models. Excellent reviews cover the development and application of CRISPR/ Cas9, [11][12][13][14][15] therefore, we will focus specifically on disease modelling for the liver. We will first elaborate on some of the approaches used to generate CRISPR/Cas9-modified animals, before discussing recently published examples of human liver disease models.…”