Modeling mitochondrial DNA diseases: from base editing to pluripotent stem-cell-derived organoids.

ABSTRACT: Mitochondrial DNA (mtDNA) diseases are multi-systemic disorders caused by mutations affecting a fraction or the entirety of mtDNA copies. Currently, there are no approved therapies for the majority of mtDNA diseases. Challenges associated with engineering mtDNA have in fact hindered the study of mtDNA defects. Despite these difficulties, it has been possible to develop valuable cellular and animal models of mtDNA diseases. Here, we describe recent advances in base editing of mtDNA and the generation of three-dimensional organoids from patient-derived human-induced pluripotent stem cells (iPSCs). Together with already available modeling tools, the combination of these novel technologies could allow determining the impact of specific mtDNA mutations in distinct human cell types and might hel

SUBMITTER: Tolle I 

PROVIDER: S-EPMC10074100 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature