Gene therapy for the mitochondrial genome: Purging mutations, pacifying ailments

Abstract

In the recent years, the reported cases of mitochondrial disorders have reached a colossal number. These disorders spawn a sundry of pathological conditions, which lead to pernicious symptoms and even fatality. Due to the unpredictable etiologies, mitochondrial diseases are putatively referred to as "mystondria" (mysterious diseases of mitochondria). Although present-day research has greatly improved our understanding of mitochondrial disorders, effective therapeutic interventions are still at the precursory stage. The conundrum becomes further complicated because these pathologies might occur due to either mitochondrial DNA (mtDNA) mutations or due to mutations in the nuclear DNA (nDNA), or both. While correcting nDNA mutations by using gene therapy (replacement of defective genes by delivering wild-type (WT) ones into the host cell, or silencing a dominant mutant allele that is pathogenic) has emerged as a promising strategy to address some mitochondrial diseases, the complications in correcting the defects of mtDNA in order to renovate mitochondrial functions have remained a steep challenge. In this review, we focus specifically on the selective gene therapy strategies that have demonstrated prospects in targeting the pathological mutations in the mitochondrial genome, thereby treating mitochondrial ailments.

Keywords: Gene therapy; Mitochondrial diseases; Mystondria; mtDNA mutations.