Liver gene transfer for metabolite detoxification in inherited metabolic diseases

• Published in: FEBS letters Vol. 598; no. 19; pp. 2372 - 2384
• Main Authors: D'Alessio, Alfonso M., Boffa, Iolanda, De Stefano, Lucia, Soria, Leandro R., Brunetti‐Pierri, Nicola
• Format: Journal Article
• Language: English
• Published: England 01.10.2024
• Subjects: AAV; gene therapy; inherited metabolic disorders; lipid nanoparticles; liver; metabolite detoxification; gene therapy; lipid nanoparticles; inherited metabolic disorders; liver; AAV; metabolite detoxification
• ISSN: 0014-5793; 1873-3468; 1873-3468
• DOI: 10.1002/1873-3468.14957

Inherited metabolic disorders (IMDs) are a growing group of genetic diseases caused by defects in enzymes that mediate cellular metabolism, often resulting in the accumulation of toxic substrates. The liver is a highly metabolically active organ that hosts several thousands of chemical reactions. As such, it is an organ frequently affected in IMDs. In this article, we review current approaches for liver‐directed gene‐based therapy aimed at metabolite detoxification in a variety of IMDs. Moreover, we discuss current unresolved challenges in gene‐based therapies for IMDs. The liver is a highly metabolically active organ. In several inherited metabolic disorders (IMDs), the enzyme deficiency results in increased concentrations of toxic metabolites and tissue damage. Delivery of nucleic acids (DNA or RNA) to hepatocytes by viral or nonviral vectors can prevent metabolite intoxication. In this article, we review approaches and challenges for liver‐directed gene therapy in selected IMDs.