Gene editing technology as an approach to the treatment of liver diseases

ABSTRACT

Introduction: More than 100 liver-related disorders are caused by mutations in a single gene. These include both inherited and acquired genetic disorders. The development of nucleic acid-based therapies for liver diseases has been severely restricted due to many undesirable side effects and methodological limitations.

Areas covered: In recent years, however, efforts have been intensified to address these issues, and to develop liver-targeted approaches using novel gene editing technologies, including ZFN, TALEN, CRISPR/Cas and PITCh. While each of these methods utilizes a distinct mechanism of gene modification at the genomic level, they all are dependent on an efficient delivery system to the target site within the host cell. This review will provide an overview on current and emerging therapeutic strategies for the treatment of liver diseases.

Expert opinion: Clinical trials for liver gene therapy have entered an exciting stage and are already showing promise with the development of novel technologies and delivery options. A deeper understanding of off-target effects produced by gene editing approaches and immune responses generated in host cells by gene carriers is needed to fully realize their potential.

KEYWORDS:

• Gene editing
• liver
• viral vectors
• non-viral vectors
• gene therapy

Article highlights

• Gene therapy for the treatment of liver diseases is an attractive option because many of them are caused by mutation(s) in a single gene.

• While a number of strategies have been implemented for gene correction and repair, they have encountered significant challenges. Advent in genome editing techniques has produced exciting results recently, suggesting that gene therapy in the clinic is within our reach.

• Refinement of various delivery methods will further enhance our ability to carry out clinical gene therapy trials successfully.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.