Gene therapy for liver enzyme deficiencies: what have we learned from models for Crigler–Najjar and tyrosinemia?

Abstract

The liver is the site of numerous metabolic inherited diseases. It has unique features that make it compliant to various gene therapy approaches. Many vector types and gene delivery strategies have been evaluated during the past 20 years in a number of animal models of metabolic liver diseases. However, the complete cure of inherited liver deficiencies by gene therapy in relevant animal models were only reported recently. These successes were achieved thanks to major advances in vector technology. In this review, we will focus on Crigler-Najjar disease and hereditary tyrosinemia, two paradigmatic examples of the two categories of enzymatic liver deficiencies: type I, in which the genetic defect does not affect liver histology; and type II, in which liver lesions are present.

Keywords::

• AAV
• adenovirus
• Crigler–Najjar
• gene therapy
• lentivirus
• liver
• liver repopulation
• tyrosinemia
• vector

Financial & competing interests disclosure

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.

No writing assistance was utilized in the production of this manuscript.