Towards gene therapy of mitochondrial disorders

Abstract

Mitochondrial disorders are characterized by protein deficiencies affecting the structure and function of mitochondria. The protein deficiencies are caused by mutations either in a nuclear gene or in the mitochondrial genome. Most current approaches to gene therapy of mitochondrial diseases aim at expression of the corrective gene sequence by nuclear/cytoplasmic expression. However, the mitochondrial genome and its autonomous expression system offer the potential of an alternative gene therapy strategy: the introduction of nuclear gene sequences into the mitochondrial genome and their expression by the mitochondrial gene expression system. In addition to its potential for gene therapy, the introduction and expression of an exogenous gene in mitochondria would provide an invaluable tool towards the understanding of mitochondrial genome expression and its regulation.