Liver-directed gene-based therapies for inborn errors of metabolism

Abstract

Introduction: Inborn errors of metabolism include several genetic disorders due to disruption of cellular biochemical reactions. Although individually rare, collectively they are a large and heterogenous group of diseases affecting a significant proportion of patients. Available treatments are often unsatisfactory. Liver-directed gene therapy has potential for treatment of several inborn errors of metabolism. While lentiviral vectors and lipid nanoparticle-mRNA have shown attractive features in preclinical studies and still have to be investigated in humans, adeno-associated virus (AAV) vectors have shown clinical success in both preclinical and clinical trials for in vivo liver-directed gene therapy.

Areas covered: In this review, we discussed the most relevant clinical applications and the challenges of liver-directed gene-based approaches for therapy of inborn errors of metabolism.

Expert opinion: Challenges and prospects of clinical gene therapy trials and preclinical studies that are believed to have the greatest potential for clinical translation are presented.

Keywords: Liver-directed gene therapy; adeno-associated virus; biochemical genetics; clinical trials; gene therapy; inborn errors of metabolism.