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

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.

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.

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