Work

Gene therapy and mRNA drugs approach for mitochondrial OXPHOS deficiencies

Year: 2025

Type: article

Abstract: Mitochondrial disorders are a clinically heterogeneous group of diseases due to defects in nuclear or mitochondrial DNA-encoded genes leading to mitochondrial dysfunction and oxidative phosphorylation deficiency in the affected tissues. The dual genetic controls, the biochemical heterogeneity, and the clinical variability challenge the development of effective treatment. In this review, we focus on gene therapy and mRNA drug approaches for nuclear-encoded gene defects causing isolated, combined, or multiple oxidative phosphorylation defects and mitochondrial-encoded gene defects for which a gene replacement approach has been tested, and on the allotopic expression of mtDNA genes. An overview of the available in vitro and in vivo disease models and pre-clinical data of safety and efficacy is provided and highlights challenges in correcting the biochemical defect in the most affected tissues. Future perspectives with the use of novel gene editing approaches or gene replacement delivery with nanoparticles are also considered as a novel strategy for treating mitochondrial disorders.

Source: Molecular Therapy

DOI: 10.1016/j.ymthe.2025.09.036

Authors: Caterina Garone, Silvia Sabeni, Sara Carli

Institutions: Istituto delle Scienze Neurologiche di Bologna, University of Bologna

Language: English

Topic: Mitochondrial Function and Pathology

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500