Recent advances in mitochondrial replacement therapy and its future expectations

Abstract

The prevention of mitochondrial diseases is particularly important due to the lack of specific therapies. Therefore, mitochondrial replacement therapy (MRT) is expected to be a technology to prevent mitochondrial diseases. Admittedly, this technology sparked a lot of controversy and discussion. In this article, we review the recent advances in MRT, discuss its safety and ethical issues, and finally explore its potential to completely block the inheritance of mitochondrial diseases.

Keywords

mitochondrial diseases / mitochondrial replacement therapy (MRT) / mtDNA

References

[1] ZhangJ, LiuH, LuoS, et al. Live birth derived from oocyte spindle transfer to prevent mitochondrial disease. Reprod Biomed Online. 2017;34(4):361-368.

[2] LiuZ, MerhiZ, ZhangJ, et al. Response: first birth following spindle transfer—should we stay or should we go? Reprod Biomed Online. 2017;35(5):546-547.

[3] Costa-BorgesN, Nikitos E, SpäthK, et al. First pilot study of maternal spindle transfer for the treatment of repeated in vitro fertilization failures in couples with idiopathic infertility. Fertil Steril. 2023;119(6):964-973.

[4] PenningsG. Enucleated oocyte donation: first for infertility treatment, then for mitochondrial diseases. J Assist Reprod Genet. 2022;39(3):605-608.

[5] AryamvallyA, MyersMF, HuangT, et al. Mitochondrial replacement therapy: genetic counselors’ experiences, knowledge, and opinions. J Genet Couns. 2021;30(3):828-837.

[6] Gómez-TatayL, Hernández-Andreu JM, AznarJ. Mitochondrial modification techniques and ethical issues. J Clin Med. 2017;6(3):25.

[7] CallawayE. First UK children born using three-person IVF: what scientists want to know. Nature. 2023;617(7961):443-444.

[8] Australian government. Mitochondrial Donation Law Reform (Maeve’s Law) Act 2022. Accessed 01 April, 2022 https://www.legislation.gov.au/C2022A00026/latest/text

[9] ZouW, SloneJ, CaoY, et al. Mitochondria and their role in human reproduction. DNA Cell Biol. 2020;39(8):1370-1378.

[10] ZouW, Chezhian J, YuT, et al. Dissecting the roles of the nuclear and mitochondrial genomes in a mouse model of autoimmune diabetes. Diabetes. 2024;73(1):108-119.

[11] MaH, Van Dyken C, DarbyH, et al. Germline transmission of donor, maternal and paternal mtDNA in primates. Hum Reprod. 2021;36(2):493-505.

[12] KangE, WuJ, GutierrezNM, et al. Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. Nature. 2016;540(7632):270-275.

[13] LiaoX, LiW, LinK, et al. Significant decrease of maternal mitochondria carryover using optimized spindle-chromosomal complex transfer. PLoS Biol. 2023;21(10):e3002313.

[14] LiW, LiaoX, LinK, et al. Earlier second polar body transfer and further mitochondrial carryover removal for potential mitochondrial replacement therapy. MedComm (2020). 2023;4(3):e217.

[15] TangM, Guggilla RR, GansemansY, et al. Comparative analysis of different nuclear transfer techniques to prevent the transmission of mitochondrial DNA variants. Mol Hum Reprod. 2019;25(12):797-810.

[16] WangT, ShaH, JiD, et al. Polar body genome transfer for preventing the transmission of inherited mitochondrial diseases. Cell. 2014;157(7):1591-1604.

[17] MaH, O’Neil RC, Marti GutierrezN, et al. Functional human oocytes generated by transfer of polar body genomes. Cell Stem Cell. 2017;20(1):112-119.

[18] QiS, WangW, XueX, et al. Single-cell multiomics analyses of spindle-transferred human embryos suggest a mostly normal embryonic development. PLoS Biol. 2022;20(8):e3001741.

[19] CravenL, MurphyJ, TurnbullDM, et al. Scientific and ethical issues in mitochondrial donation. New Bioeth. 2018;24(1):57-73.

RIGHTS & PERMISSIONS

2024 The Author(s). Clinical and Translational Discovery published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.