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

Research output: Contribution to journalReview article

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)421-433
Number of pages13
JournalReproductive Medicine and Biology
Volume17
Issue number4
DOIs
Publication statusPublished - 2018 Oct

Keywords

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

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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