Mitochondrial DNA (mtDNA) and mitochondrial replacement therapy

AccessScience ◽  
2015 ◽  
Keyword(s):  
Mitochondrial Dna ◽  
Replacement Therapy ◽  
Mitochondrial Replacement Therapy

scholarly journals Mitochondrial replacement therapy and the “three parent baby”

SURG Journal ◽  
2017 ◽  
Vol 9 (1) ◽  
pp. 48-56 ◽  
Author(s):  
Suzanna Tai
Keyword(s):  
Mitochondrial Dna ◽  
Replacement Therapy ◽  
Polar Body ◽  
Genetic Material ◽  
Eukaryotic Cells ◽  
Mtdna Mutation ◽  
Donor Oocyte ◽  
Polar Bodies ◽  
Mitochondrial Replacement Therapy ◽  
Pronuclear Transfer

The mitochondria contained in eukaryotic cells have their own DNA, and heritable mutations in mitochondrial DNA (mtDNA) can cause a variety of disorders in humans. A new therapy, mitochondrial replacement therapy (MRT), is currently being developed to address these mitochondrial disorders by eliminating the mutated mtDNA from the germline. The two main MRT techniques are pronuclear transfer, conducted in the zygote after fertilization, and spindle-chromosomal complex transfer, conducted in the oocyte before fertilization. In pronuclear transfer, the pronuclei from a zygote affected by a mtDNA mutation are transferred to an enucleated normal zygote. In spindle-chromosomal complex transfer, the genetic material from an oocyte affected by a mtDNA mutation is inserted into the cytoplasm of a donor oocyte that contains healthy mitochondria. A third method, polar body genome transfer, attempts to increase the efficiency of the above techniques by using polar bodies to supply the genetic material. While MRT is legally and ethically controversial, it has recently been implemented successfully in a clinical setting.

scholarly journals Mito-nuclear Incompatibilities and Mitochondrial Replacement Therapy

2016 ◽  
Author(s):  
Adam Eyre-Walker
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Replacement Therapy ◽  
Nuclear Genome ◽  
Reproductive Technology ◽  
Mitochondrial Mutations ◽  
Mitochondrial Replacement Therapy ◽  
Human Reproductive ◽  
Nuclear Genomes ◽  
Native Strains

AbstractMitochondrial replacement therapy (MRT) is a human reproductive technology by which the mitochondria of a recipient’s eggs are effectively replaced by those of a donor, potentially eliminating harmful mitochondrial mutations carried by the recipient. However, concerns have been raised that MRT may lead to problems due to incompatibilities between the nuclear genome of the recipient and mitochondrial genome of the donor. Whether this is likely to be a problem is investigated using 226 estimates, taken from the literature, of the effect of replacing the “native” by a “foreign” mitochondrial DNA (mtDNA) from the same species in a variety of animals. In approximately half of the cases (45%), strains with the foreign mtDNA have higher fitness than those with the native mtDNA, and on average the native strains are only 3% fitter. Based on these results it is argued that incompatibilities between the mitochondrial and nuclear genomes are not likely to be a problem for MRT.

scholarly journals Development of mitochondrial replacement therapy: A review

Heliyon ◽  
2020 ◽  
Vol 6 (9) ◽  
pp. e04643
Author(s):  
Hitika Sharma ◽  
Drishtant Singh ◽  
Ankush Mahant ◽  
Satwinder Kaur Sohal ◽  
Anup Kumar Kesavan ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Mitochondrial Replacement Therapy

scholarly journals Modulating mitochondrial quality in disease transmission: towards enabling mitochondrial DNA disease carriers to have healthy children

2016 ◽  
Vol 44 (4) ◽  
pp. 1091-1100 ◽  
Author(s):  
Alan Diot ◽  
Eszter Dombi ◽  
Tiffany Lodge ◽  
Chunyan Liao ◽  
Karl Morten ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Disease Transmission ◽  
Stochastic Dynamics ◽  
Genetic Diagnosis ◽  
Healthy Children ◽  
Non Invasive ◽  
Incurable Disease ◽  
Mitochondrial Replacement Therapy ◽  
Quality Control Mechanism ◽  
Cellular Components

One in 400 people has a maternally inherited mutation in mtDNA potentially causing incurable disease. In so-called heteroplasmic disease, mutant and normal mtDNA co-exist in the cells of carrier women. Disease severity depends on the proportion of inherited abnormal mtDNA molecules. Families who have had a child die of severe, maternally inherited mtDNA disease need reliable information on the risk of recurrence in future pregnancies. However, prenatal diagnosis and even estimates of risk are fraught with uncertainty because of the complex and stochastic dynamics of heteroplasmy. These complications include an mtDNA bottleneck, whereby hard-to-predict fluctuations in the proportions of mutant and normal mtDNA may arise between generations. In ‘mitochondrial replacement therapy’ (MRT), damaged mitochondria are replaced with healthy ones in early human development, using nuclear transfer. We are developing non-invasive alternatives, notably activating autophagy, a cellular quality control mechanism, in which damaged cellular components are engulfed by autophagosomes. This approach could be used in combination with MRT or with the regular management, pre-implantation genetic diagnosis (PGD). Mathematical theory, supported by recent experiments, suggests that this strategy may be fruitful in controlling heteroplasmy. Using mice that are transgenic for fluorescent LC3 (the hallmark of autophagy) we quantified autophagosomes in cleavage stage embryos. We confirmed that the autophagosome count peaks in four-cell embryos and this correlates with a drop in the mtDNA content of the whole embryo. This suggests removal by mitophagy (mitochondria-specific autophagy). We suggest that modulating heteroplasmy by activating mitophagy may be a useful complement to mitochondrial replacement therapy.

scholarly journals Mitochondrial replacement therapy and parenthood

2015 ◽  
Vol 26 (3-4) ◽  
pp. 198-205 ◽  
Author(s):  
Mirko Daniel Garasic ◽  
Daniel Sperling
Keyword(s):  
Replacement Therapy ◽  
Mitochondrial Replacement Therapy
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