CRISPR/Cas9-related technologies in liver diseases: from feasibility to future diversity

Abstract

Liver diseases are one of the leading causes of mortality in the world, mainly caused by different etiological agents, alcohol consumption, viruses, drug intoxication, and malnutrition. The maturation of gene therapy has heralded new avenues for developing effective interventions for these diseases. Derived from a remarkable microbial defense system, clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins 9 system (CRISPR/Cas9 system) is driving innovative applications from basic biology to biotechnology and medicine. Recently, the mutagenic function of CRISPR/Cas9 system has been widely adopted for genome and disease research. In this review, we describe the development and applications of CRISPR/Cas9 system on liver diseases for research or translational applications, while highlighting challenges as well as future avenues for innovation.

CRISPR/Cas9 gene editing: New hope for Alzheimer's disease therapeutics

“…As a gene-editing tool, CRISPR/Cas9 holds promise by correcting specific gene sequences and having significant potential for the treatment of AD and other human diseases [90] , [91] , [92] , [93] , [94] , [95] , [96] ( Fig. 5 ).…”

Novel vectors and approaches for gene therapy in liver diseases

“…34,35 However, due to its simplicity, high efficiency, and easy customization, CRISPR/Cas9 is the gene editing tool of choice nowadays. [36][37][38][39] Several clinical trials using CRISPR/Cas9…”

“…Nevertheless, at the preclinical stage, the use of CRISPR/Cas9 targeting the liver is being applied to HemA and HemB via targeted therapeutic gene integration, and to glycogen storage disorder 1a (GSD1a) and AATdeficiency by precise correction of gene mutations. 38 Gene editing can also be used as a genetic MPR or SRT strategy, as has been shown for the treatment of familiar hypercholesterolemia (FH), primary hyperoxaluria type 1 (PH1), and tyrosinemia via the elimination of proprotein convertase subtilisin/kexin type 9 (PCSK9), glycolate oxidase (GO)/lactate dehydrogenase (LDH) expression, and hydroxyphenylpyruvate dioxygenase (HPD), respectively. [39][40][41] Chemically modified small interfering RNAs (siRNA) and antisense oligonucleotides (ASOs)…”

“… 34 , 35 However, due to its simplicity, high efficiency, and easy customisation, CRISPR/Cas9 is the gene editing tool of choice nowadays. [36] , [37] , [38] , [39] Several clinical trials using CRISPR/Cas9 are ongoing or about to be initiated but most of them are based on ex vivo editing for the treatment of cancer, and a very small number target genetic diseases. Nevertheless, at the preclinical stage, the use of CRISPR/Cas9 targeting the liver is being applied to HemA and HemB via targeted therapeutic gene integration, and to glycogen storage disorder 1a (GSD1a) and AAT deficiency by precise correction of gene mutations.…”

CRISPR-Cas and Its Wide-Ranging Applications: From Human Genome Editing to Environmental Implications, Technical Limitations, Hazards and Bioethical Issues

“…Pavani and collaborators showed its use in the treatment of beta-thalassemia [ 52 ] and there are ongoing projects for the treatment of AIDS [ 53 ]. Several works exist describing a possible CRISPR-based approach in the treatment of liver diseases such as viral hepatitis, hepatocellular carcinoma and hereditary tyrosinemia type I (reviewed in [ 54 ]). This system has also been used to specifically remove entire chromosomes from the genome.…”