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Published on: June 30, 2023
RNA-mediated restoration of mitochondrial function in cells harboring a Kearns Sayre Syndrome mutation
Biraj Mahato1, Sukanta Jash, Samit Adhya
1Genetic Engineering Laboratory, Indian Institute of Chemical Biology (C.S.I.R), 4 Raja S. C. Mullick Road, Calcutta 700032, India.
Abstract:
Mutations in mitochondrial DNA (mtDNA) generate multi-system disorders due to failure of ATP production. A cybrid containing a 1.9-kb mtDNA deletion from a patient with Kearns Sayre Syndrome is respiration-defective and grows glycolytically. When treated with a ribonucleoprotein (RNP) complex of polycistronic RNA 1 (pcRNA1) containing mtDNA-encoded genes and a multi-subunit carrier complex R8, full-length pcRNA1 was transported to mitochondria. Translation of the pcRNA1-encoded mRNAs was observed in mitochondria from RNP-treated cells. Respiration of the cybrid was rescued to approximately 90% of normal within hours, switching the cells to aerobic growth. These findings have implications for the development of effective mitochondrial gene therapy.
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