Inborn errors of metabolism (IEM) are disorders affecting human biochemical pathways and represent attractive targets for gene therapy because of their severity, high overall prevalence, lack of effective treatments, and possibility of early diagnosis through newborn screening. The liver is a central organ involved in several metabolic reactions and is a favorite target for gene therapy in many IEM. Adeno-associated virus (AAV) vectors have emerged in the last years as the preferred vectors for in vivo gene delivery. Gene replacement strategies are aimed either at correcting liver disease or providing a source for production and secretion of the lacking enzyme for cross-correction of other tissues. A number of preclinical studies have been conducted in the last years and, for several diseases, gene therapy has reached the clinical stage, with a growing number of ongoing clinical trials. Moreover, recent applications of genome editing to the field of inherited metabolic diseases have further expanded potential therapeutic possibilities. This review describes relevant clinical gene therapy studies for IEM with particular attention to current obstacles and drawbacks.
Keywords: AAV; adeno-associated virus vectors; gene therapy; inborn errors of metabolism; liver.