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Elimination of Mutant mtDNA by an Optimized mpTALEN Restores Differentiation Capacities of Heteroplasmic MELAS-iPSCs

Naoki Yahata, Hiroko Boda, Ryuji Hata

2020Molecular Therapy — Methods & Clinical Development13 citationsDOIOpen Access PDF

Abstract

, which was relieved by decreasing the heteroplasmy level with G13513A-mpTALEN. Additionally, drug-inducible, myogenic differentiation 1 (MYOD)-transfected MELAS-iPSCs (MyoD-iPSCs) efficiently differentiated into myosin heavy chain-positive myocytes, with or without mutant mtDNA. Hence, heteroplasmic MyoD-iPSCs controlled by fine-tuned mpTALENs may contribute to a detailed analysis of the relationship between mutation load and cellular phenotypes in disease modeling.

Topics & Concepts

HeteroplasmyMitochondrial DNABiologyMELAS syndromeInduced pluripotent stem cellMitochondrial myopathyLactic acidosisGeneticsMolecular biologyMitochondrial diseaseMyoDCell biologyCellular differentiationBiochemistryGeneEmbryonic stem cellMitochondrial Function and PathologyCRISPR and Genetic EngineeringRNA and protein synthesis mechanisms
Elimination of Mutant mtDNA by an Optimized mpTALEN Restores Differentiation Capacities of Heteroplasmic MELAS-iPSCs | Litcius