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Reprod Med Biol. 2018 Sep 19;17(4):421-433. doi: 10.1002/rmb2.12230. eCollection 2018 Oct.

Mitochondrial replacement therapy and assisted reproductive technology: A paradigm shift toward treatment of genetic diseases in gametes or in early embryos.

Author information

1
Department of Obstetrics & Gynecology Tohoku University School of Medicine Sendai Japan.

Abstract

Background:

Recent technological development allows nearly complete replacement of the cytoplasm of egg/embryo, eliminating the transmission of undesired defective mitochondria (mutated mitochondrial DNA: mtDNA) for patients with inherited mitochondrial diseases, which is called mitochondrial replacement therapy (MRT).

Methods:

We review and summarize the mitochondrial biogenesis and mitochondrial diseases, the research milestones and future research agenda of MRT and also discuss MRT-derived potential application in common assisted reproductive technology (ART) treatment for subfertile patients.

Main findings:

Emerging techniques, involving maternal spindle transfer (MST) and pronuclear transfer (PNT), have demonstrated in preventing carryover of the unbidden (mutated) mtDNA in egg or in early embryos. The House of Parliament in the United Kingdom passed regulations permitting the use of MST and PNT in 2015. Furthermore, the Human Fertilization and Embryology Authority (HFEA) to granted licenses world first use of those techniques in March 2017. However, recent evidence demonstrated gradual loss of donor mtDNA and reversal to the nuclear DNA-matched haplotype in MRT derivatives.

Conclusion:

While further studies are needed to clarify mitochondrial biogenesis responsible for reversion, ruling in United Kingdom may shift the current worldwide consensus that prohibits gene modification in human gametes or embryos, toward allowing the correction of altered genes in germline.

KEYWORDS:

germ line gene therapy; maternal spindle transfer (MST); mitochondrial bottleneck effect; mitochondrial diseases; mitochondrial replacement therapy (MRT)

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