← Back to Search
Novel Reproductive Technologies To Prevent Mitochondrial Disease
L. Craven, M. Tang, G. Gorman, P. De Sutter, B. Heindryckx
Published 2017 · Biology, Medicine
Download PDFAnalyze on Scholarcy
BACKGROUND The use of nuclear transfer (NT) has been proposed as a novel reproductive treatment to overcome the transmission of maternally-inherited mitochondrial DNA (mtDNA) mutations. Pathogenic mutations in mtDNA can cause a wide-spectrum of life-limiting disorders, collectively known as mtDNA disease, for which there are currently few effective treatments and no known cures. The many unique features of mtDNA make genetic counselling challenging for women harbouring pathogenic mtDNA mutations but reproductive options that involve medical intervention are available that will minimize the risk of mtDNA disease in their offspring. This includes PGD, which is currently offered as a clinical treatment but will not be suitable for all. The potential for NT to reduce transmission of mtDNA mutations has been demonstrated in both animal and human models, and has recently been clinically applied not only to prevent mtDNA disease but also for some infertility cases. In this review, we will interrogate the different NT techniques, including a discussion on the available safety and efficacy data of these technologies for mtDNA disease prevention. In addition, we appraise the evidence for the translational use of NT technologies in infertility. OBJECTIVE AND RATIONALE We propose to review the current scientific evidence regarding the clinical use of NT to prevent mitochondrial disease. SEARCH METHODS The scientific literature was investigated by searching PubMed database until Jan 2017. Relevant documents from Human Fertilisation and Embryology Authority as well as reports from both the scientific and popular media were also implemented. The above searches were based on the following key words: 'mitochondria', 'mitochondrial DNA'; 'mitochondrial DNA disease', 'fertility'; 'preimplantation genetic diagnosis', 'nuclear transfer', 'mitochondrial replacement' and 'mitochondrial donation'. OUTCOMES While NT techniques have been shown to effectively reduce the transmission of heteroplasmic mtDNA variants in animal models, and increasing evidence supports their use to prevent the transmission of human mtDNA disease, the need for robust, long-term evaluation is still warranted. Moreover, prenatal screening would still be strongly advocated in combination with the use of these IVF-based technologies. Scientific evidence to support the use of NT and other novel reproductive techniques for infertility is currently lacking. WIDER IMPLICATIONS It is mandatory that any new ART treatments are first adequately assessed in both animal and human models before the cautious implementation of these new therapeutic approaches is clinically undertaken. There is growing evidence to suggest that the translation of these innovative technologies into clinical practice should be cautiously adopted only in highly selected patients. Indeed, given the limited safety and efficacy data, close monitoring of any offspring remains paramount.
This paper references
Cytoplasmic transfer in assisted reproduction.
J. Barritt (2001)
Incompatibility between Nuclear and Mitochondrial Genomes Contributes to an Interspecies Reproductive Barrier.
H. Ma (2016)
Healthy baby girl born following preimplantation genetic diagnosis for mitochondrial DNA M.8993t > G mutation
DR Thorburn (2009)
Cumulative Live-birth Rates after In Vitro Fertilization
S. Corson (2009)
Modulating mitochondrial quality in disease transmission: towards enabling mitochondrial DNA disease carriers to have healthy children
A. Diot (2016)
Embryo developmental capability and pregnancy outcome are related to the mitochondrial DNA copy number and ooplasmic volume
Yukitaka Murakoshi (2013)
Gene therapy for progeny of mito-mice carrying pathogenic mtDNA by nuclear transplantation.
A. Sato (2005)
Mitochondrial DNA content and 4977 bp deletion in unfertilized oocytes.
C. W. Chan (2005)
Germ-line therapy to cure mitochondrial disease: protocol and ethics of in vitro ovum nuclear transplantation.
D. Rubenstein (1995)
MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins
S. Calvo (2016)
Maternal diabetes and oocyte quality.
Q. Wang (2010)
MitoTALEN: A General Approach to Reduce Mutant mtDNA Loads and Restore Oxidative Phosphorylation Function in Mitochondrial Diseases.
Masami Hashimoto (2015)
Prevention of mitochondrial disease inheritance by assisted reproductive technologies: prospects and challenges.
A. Yabuuchi (2012)
Reprogramming within hours following nuclear transfer into mouse but not human zygotes.
D. Egli (2011)
Altered Levels of Mitochondrial DNA Are Associated with Female Age, Aneuploidy, and Provide an Independent Measure of Embryonic Implantation Potential
E. Fragouli (2015)
Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins
T. Hussein (2005)
Mitochondrial transfer between oocytes: potential applications of mitochondrial donation and the issue of heteroplasmy.
J. van Blerkom (1998)
Assisted reproductive technology in reproductive medicine – possibilities and limitations. Ginekol Pol 2016;87:820–823
M. Szamatowicz (2016)
Emerging therapies for mitochondrial disorders. Brain 2016;139:1633–1648
H Nightingale (2016)
G. Gorman (2016)
Treatment option for sperm- or oocyte-related fertilization failure: assisted oocyte activation following diagnostic heterologous ICSI.
B. Heindryckx (2005)
In D-loop: 40years of mitochondrial 7S DNA
T. Nicholls (2014)
[Influence of maternal age on meiotic spindle and chromosome configuration of oocytes].
W. Chen (2007)
The activity and copy number of mitochondrial DNA in ovine oocytes throughout oogenesis in vivo and during oocyte maturation in vitro
Matthew Cotterill (2013)
Selective elimination of mutant mitochondrial genomes as therapeutic strategy for the treatment of NARP and MILS syndromes.
M. Alexeyev (2008)
Mitochondria in human offspring derived from ooplasmic transplantation.
J. Barritt (2001)
Erratum to: Clinical features and heteroplasmy in blood, urine and saliva in 34 Dutch families carrying the m.3243A>G mutation
P. Laat (2012)
Eliminate mitochondrial diseases by gene editing in germ-line cells and embryos
Si Li Wang (2015)
Myoclonus epilepsy associated with ragged-red fibres (mitochondrial abnormalities): Disease entity or a syndrome?: Light- and electron-microscopic studies of two cases and review of literature
N. Fukuhara (1980)
Influence of maternal age on meiotic spindle assembly in oocytes from naturally cycling women.
D. Battaglia (1996)
Limitations of preimplantation genetic diagnosis for mitochondrial DNA diseases.
Shoukhrat Mitalipov (2014)
Complete Kinetochore Tracking Reveals Error-Prone Homologous Chromosome Biorientation in Mammalian Oocytes
Tomoya S. Kitajima (2011)
Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy.
D. Wallace (1988)
Genetic counseling and prenatal diagnosis for the mitochondrial DNA mutations at nucleotide 8993.
S. White (1999)
The impact of mitochondrial function/dysfunction on IVF and new treatment possibilities for infertility
H. Schatten (2014)
Pregnancy following transfer of ooplasm from cryopreserved-thawed donor oocytes into recipient oocytes.
S. Lanzendorf (1999)
Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer.
E. C. Spikings (2006)
Revisiting Germinal Vesicle Transfer as a Treatment for Aneuploidy in Infertile Women with Diminished Ovarian Reserve
J. Zhang (2014)
Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: A distinctive clinical syndrome
S. Pavlakis (1984)
Metaphase II nuclei generated by germinal vesicle transfer in mouse oocytes support embryonic development to term.
H. Liu (2003)
Centrioles in the beginning of human development.
A. Sathananthan (1991)
Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification
A. Handyside (1990)
Spindles, mitochondria and redox potential in ageing oocytes.
U. Eichenlaub-Ritter (2004)
Effects of granulosa cell mitochondria transfer on the early development of bovine embryos in vitro.
S. Hua (2007)
Evolutionary defined role of the mitochondrial DNA in fertility, disease and ageing.
Auke B C Otten (2015)
PGD and heteroplasmic mitochondrial DNA point mutations: a systematic review estimating the chance of healthy offspring.
D. Hellebrekers (2012)
Ooplasmic transfer in mature human oocytes.
J. Cohen (1998)
Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs
P. A. Gammage (2016)
Birth after the injection of sperm and the cytoplasm of tripronucleate zygotes into metaphase II oocytes in patients with repeated implantation failure after assisted fertilization procedures.
C. C. Huang (1999)
The effect of temperature fluctuations on the cytoskeletal organisation and chromosomal constitution of the human oocyte.
P. Almeida (1995)
Mouse consomic strains: exploiting genetic divergence between Mus m. musculus and Mus m. domesticus subspecies.
S. Gregorová (2008)
Chromosome transfer in mature oocytes
M. Tachibana (2010)
Xenomitochondrial mice: investigation into mitochondrial compensatory mechanisms.
M. Cannon (2011)
Prospect of preimplantation genetic diagnosis for heritable mitochondrial DNA diseases.
N. Dean (2003)
COMMITTEE ON THE ETHICAL AND SOCIAL POLICY CONSIDERATIONS OF NOVEL TECHNIQUES FOR PREVENTION OF MATERNAL TRANSMISSION OF MITOCHONDRIAL DNA DISEASES
A. Claiborne (2016)
Aging and the environment affect gamete and embryo potential: can we intervene?
D. Meldrum (2016)
Mitochondrial replacement therapy in reproductive medicine.
D. Wolf (2015)
Assisted reproductive technology in reproductive medicine - possibilities and limitations.
M. Szamatowicz (2016)
Pregnancy derived from human zygote pronuclear transfer in a patient who had arrested embryos after IVF.
J. Zhang (2016)
Mitochondrial donation--how many women could benefit?
G. Gorman (2015)
NARP and MILS syndromes
PA Almeida (2008)
Maternally inherited Leigh syndrome.
E. Ciafaloni (1993)
Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases.
P. Amato (2014)
Modifying the Mitochondrial Genome.
A. Patananan (2016)
The Challenges of Mitochondrial Replacement
P. Chinnery (2014)
Nuclear transplantation in the mouse embryo by microsurgery and cell fusion.
James H. McGrath (1983)
In-vitro development of mouse zygotes following reconstruction by sequential transfer of germinal vesicles and haploid pronuclei.
H. Liu (2000)
First live birth using human oocytes reconstituted by spindle nuclear transfer for mitochondrial DNA mutation causing Leigh syndrome
J. Zhang (2016)
Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants
D. Paull (2013)
Emerging therapies for mitochondrial disorders
H. Nightingale (2016)
Cytoplasmic transfer in assisted repro
J 16513–516.Barritt (2001)
Mitochondrial endonuclease G mediates breakdown of paternal mitochondria upon fertilization
Q. Zhou (2016)
A neurological perspective on mitochondrial disease
R. McFarland (2010)
Preliminary findings in germinal vesicle transplantation of immature human oocytes.
T. Takeuchi (2001)
Genetics of mitochondrial dysfunction and infertility
L. Demain (2017)
Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease
L. Craven (2010)
Genome engineering through CRISPR/Cas9 technology in the human germline and pluripotent stem cells.
R. Vassena (2016)
Transmission of mitochondrial DNA disorders: possibilities for the future
D. Brown (2006)
Multiple deletions of mitochondrial DNA are associated with the decline of motility and fertility of human spermatozoa.
S. Kao (1998)
Effect of Treating Induced Mitochondrial Damage on Embryonic Development and Epigenesis
T. Takeuchi (2005)
Mitochondrial genotype segregation during preimplantation development in mouse heteroplasmic embryos.
F. Meirelles (1998)
Preventing the transmission of pathogenic mitochondrial DNA mutations: can we achieve long-term benefits from germ-line gene transfer?
D. Samuels (2013)
Oogonial Precursor Cell-Derived Autologous Mitochondria Injection to Improve Outcomes in Women With Multiple IVF Failures Due to Low Oocyte Quality
K. Oktay (2015)
MtDNA segregation in heteroplasmic tissues is common in vivo and modulated by haplotype differences and developmental stage.
J. Burgstaller (2014)
Oocyte formation by mitotically-active germ cells purified from ovaries of reproductive age women
Yvonne A. R. White (2012)
PGD for the m.14487 T>C mitochondrial DNA mutation resulted in the birth of a healthy boy
Suzanne C E H Sallevelt (2017)
Ooplast-mediated developmental rescue of bovine oocytes exposed to ethidium bromide.
M. R. Chiaratti (2011)
Metabolic rescue in pluripotent cells from patients with mtDNA disease
H. Ma (2015)
In vitro maturation of human preovulatory oocytes reconstructed by germinal vesicle transfer.
J. Zhang (1999)
Retinitis pigmentosa, external ophthalmophegia, and complete heart block: unusual syndrome with histologic study in one of two cases.
T. Kearns (1958)
Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates
Dan Liu (2009)
Cytoplasm replacement following germinal vesicle transfer restores meiotic maturation and spindle assembly in meiotically arrested oocytes.
J. Zhang (2015)
Polar Body Genome Transfer for Preventing the Transmission of Inherited Mitochondrial Diseases
T. Wang (2014)
Blastocyst preimplantation genetic diagnosis (PGD) of a mitochondrial DNA disorder.
N. Treff (2012)
Mitochondria in human offspring
Pregnancy after cytoplasmic transfer in a couple suffering from idiopathic infertility: case report.
B. Dale (2001)
The AUGMENT SM Treatment: Physician Reported Outcomes of the Initial Global Patient Experience
M. Fakih (2015)
Mitochondrial DNA disease: new options for prevention.
L. Craven (2011)
Fertilization and early embryology: Influence of maternal age on meiotic spindle assembly oocytes from naturally cycling women
D. Battaglia (1996)
Medicinal and genetic approaches to the treatment of mitochondrial disease.
E. Schon (2003)
Germline stem cells and follicular renewal in the postnatal mammalian ovary
J. Johnson (2004)
Efficient Mitochondrial Genome Editing by CRISPR/Cas9
A. Jo (2015)
Mitochondrial Gene Replacement in Primate Offspring and Embryonic Stem Cells
M. Tachibana (2009)
Live Birth Derived From Oocyte Spindle Transfer to Prevent Mitochondrial Disease
J. Zhang (2017)
Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease
G. Gorman (2015)
Meiotic Origins of Maternal Age-Related Aneuploidy1
T. Chiang (2012)
Nuclear and cytoplasmic determinants involved in the regulation of mammalian oocyte maturation.
J. Fulka (1998)
Ovarian ageing: the role of mitochondria in oocytes and follicles.
P. May-Panloup (2016)
A Mechanism Linking Extra Centrosomes to Chromosomal Instability
Neil J Ganem (2009)
Mitochondria: participation to infertility as source of energy and cause of senescence.
M. Benkhalifa (2014)
mtDNA diversity in human populations highlights the merit of haplotype matching in gene therapies.
E. Royrvik (2016)
Research into Policy: A Brief History of Mitochondrial Donation
L. Craven (2016)
The kinetics of donor cell mtDNA in embryonic and somatic donor cell-derived bovine embryos.
C. Ferreira (2007)
Preimplantation genetic diagnosis in mitochondrial DNA disorders: challenge and success
Suzanne C E H Sallevelt (2013)
The Impact of Biopsy on Human Embryo Developmental Potential during Preimplantation Genetic Diagnosis
D. Cimadomo (2016)
The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes
T. Wai (2008)
The first polar body can be used for the production of normal offspring in mice.
T. Wakayama (1998)
A limited survey-based uncontrolled follow-up study of children born after ooplasmic transplantation in a single centre.
S. Chen (2016)
RB Blok (2014)
Cumulative live birth rates after fresh and vitrified cleavage-stage versus blastocyst-stage embryo transfer in the first treatment cycle.
A. De Vos (2016)
Birth of infant after transfer of anucleate donor oocyte cytoplasm into recipient eggs
J. Cohen (1997)
Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations
P. A. Gammage (2014)
Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans
A. Pyle (2015)
Prediction models in in vitro fertilization; where are we? A mini review
L. van Loendersloot (2014)
PGD to reduce reproductive risk: the case of mitochondrial DNA disorders.
A. Bredenoord (2008)
A systematic analysis of the suitability of preimplantation genetic diagnosis for mitochondrial diseases in a heteroplasmic mitochondrial mouse model.
J. Neupane (2014)
Skewed segregation of the mtDNA nt 8993 (T-->G) mutation in human oocytes.
R. Blok (1997)
CRISPR/Cas9 and mitochondrial gene replacement therapy: promising techniques and ethical considerations.
S. Fogleman (2016)
Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutation
J. Shoffner (1990)
Rapid mitochondrial DNA segregation in primate preimplantation embryos precedes somatic and germline bottleneck.
H. Lee (2012)
Quantification of mtDNA in single oocytes, polar bodies and subcellular components by real-time rapid cycle fluorescence monitored PCR.
N. Steuerwald (2000)
Genetic Drift Can Compromise Mitochondrial Replacement by Nuclear Transfer in Human Oocytes.
M. Yamada (2016)
A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes
L. M. Cree (2008)
Biased inheritance of mitochondria during asymmetric cell division in the mouse oocyte
C. Dalton (2013)
mtDNA mutations variously impact mtDNA maintenance throughout the human embryofetal development
J. Steffann (2015)
Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries
H. Zhang (2012)
Effects of Ooplasm Manipulation on DNA Methylation and Growth of Progeny in Mice1
Yong Cheng (2009)
Data from artificial models of mitochondrial DNA disorders are not always applicable to humans.
J. Steffann (2014)
Towards germline gene therapy of inherited mitochondrial diseases
M. Tachibana (2013)
Mitochondrial Replacement Techniques
A. Claiborne (2016)
Autophagy and ubiquitin–proteasome system contribute to sperm mitophagy after mammalian fertilization
Won-Hee Song (2016)
Mitochondrial DNA disease and developmental implications for reproductive strategies
J. Burgstaller (2015)
Preventing the transmission of mitochondrial DNA disorders using prenatal or preimplantation genetic diagnosis
Hubert J.M. Smeets (2015)
Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging
A. Ben-Meir (2015)
Artificial oocyte activation and intracytoplasmic sperm injection.
M. Nasr-Esfahani (2010)
mtDNA point mutations are present at various levels of heteroplasmy in human oocytes.
Lorraine Jacobs (2007)
Cellular Heterogeneity in the Level of mtDNA Heteroplasmy in Mouse Embryonic Stem Cells.
J. Neupane (2015)
Mutation-free baby born from a mitochondrial encephalopathy, lactic acidosis and stroke-like syndrome carrier after blastocyst trophectoderm preimplantation genetic diagnosis.
B. Heindryckx (2014)
Modifying the mitochondrial genome to enhance animal production
J. C. S. John (2014)
Functional Human Oocytes Generated by Transfer of Polar Body Genomes.
H. Ma (2017)
Cumulative live birth rates after one or more complete cycles of IVF: a population-based study of linked cycle data from 178,898 women.
D. McLernon (2016)
The role of centrosomes in mammalian fertilization and its significance for ICSI.
H. Schatten (2009)
Mitochondrial Replacement, Evolution, and the Clinic
K. Reinhardt (2013)
A non-enzymatic function of 17β-hydroxysteroid dehydrogenase type 10 is required for mitochondrial integrity and cell survival
Katharina Rauschenberger (2010)
Polar body biopsy.
M. Montag (2013)
Adult phenotype in the mouse can be affected by epigenetic events in the early embryo.
W. Reik (1993)
Therapeutic potential of somatic cell nuclear transfer for degenerative disease caused by mitochondrial DNA mutations
Gareth D. Greggains (2014)
Segregation of mtDNA Throughout Human Embryofetal Development: m.3243A > G as a Model System
S. Monnot (2011)
Mitochondria and the death of oocytes
D. Krakauer (2000)
Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations
Eunju Kang (2016)
Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease
L. Hyslop (2016)
In vitro maturation of human oocytes: Its role in infertility treatment and new possibilities
E. Chang (2014)
Poor correlations in the levels of pathogenic mitochondrial DNA mutations in polar bodies versus oocytes and blastomeres in humans.
N. Gigarel (2011)
Mitochondrial genotype segregation in a mouse heteroplasmic lineage produced by embryonic karyoplast transplantation.
F. Meirelles (1997)
Concise Reviews: Assisted Reproductive Technologies to Prevent Transmission of Mitochondrial DNA Disease
J. Richardson (2015)
A national perspective on prenatal testing for mitochondrial disease
V. Nesbitt (2014)
Analysis of mtDNA variant segregation during early human embryonic development: a tool for successful NARP preimplantation diagnosis
J. Steffann (2005)
Mitochondrial disorders: genetics, counseling, prenatal diagnosis and reproductive options.
D. Thorburn (2001)
Mitochondria transfer (mit) into oocyte from autologous cumulus granulosa cells (cgcs)
C. R. Tzeng (2004)
Poor correlation between polar bodies and blastomere mutation load in a patient with m.3243A>G tRNALeu(UUR) point mutation.
M. Vandewoestyne (2012)
Single-Cell DNA-Methylation Analysis Reveals Epigenetic Chimerism in Preimplantation Embryos
C. Lorthongpanich (2013)
Mouse-rabbit germinal vesicle transfer reveals that factors regulating oocyte meiotic progression are not species-specific in mammals.
G. Li (2001)
Assessment of nuclear transfer techniques to prevent the transmission of heritable mitochondrial disorders without compromising embryonic development competence in mice.
Jitesh Neupane (2014)
Deficit of mitochondria-derived ATP during oxidative stress impairs mouse MII oocyte spindles
Who Collaborative (2006)
Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies
I. Holt (1988)
Selective Elimination of Mitochondrial Mutations in the Germline by Genome Editing
P. Reddy (2015)
A Drosophila model for mito-nuclear diseases generated by an incompatible interaction between tRNA and tRNA synthetase
Marissa A. Holmbeck (2015)
A reliable technique of nuclear transplantation for immature mammalian oocytes.
T. Takeuchi (1999)
Mitochondrial DNA transmission, replication and inheritance: a journey from the gamete through the embryo and into offspring and embryonic stem cells.
J. S. St John (2010)
Selection of a mtDNA sequence variant in hepatocytes of heteroplasmic mice is not due to differences in respiratory chain function or efficiency of replication.
B. Battersby (2001)
Transfer of germinal vesicle to ooplasm of young mice could not rescue ageing-associated chromosome misalignment in meiosis of oocytes from aged mice.
Longbo Cui (2005)
A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues.
G. Cortopassi (1992)
Participation of the female pronucleus derived from the second polar body in full embryonic development of mice.
T. Wakayama (1997)
This paper is referenced by
Autologous mitochondrial microinjection; a strategy to improve the oocyte quality and subsequent reproductive outcome during aging
H. Mobarak (2019)
Scientific and Ethical Issues in Mitochondrial Donation
L. Craven (2018)
Deleterious in late life mitochondrial alleles and aging: secrets of Japanese centenarians
A. Mikhailova (2019)
Research Progress on Mitochondrial Replacement Therapies in Reproductive Medicine
Lingbin Qi (2019)
Mitochondrial Genetic Drift after Nuclear Transfer in Oocytes
M. Yamada (2020)
Mitochondrial Donation and UK Biomedical Politics
R. Dimond (2018)
Advances in methods for reducing mitochondrial DNA disease by replacing or manipulating the mitochondrial genome
P. K. Rai (2018)
Использование различных методов биопсии эмбриона для преимплантационного генетического тестирования (обзор литературы)
Kseniya Vladislavovna Krasnopolskaya (2019)
A case‐comparison study of pregnant women with mitochondrial disease – what to expect?
C. Feeney (2019)
Futuristic Look at Genetic and Birth Defect Diagnoses and Treatments.
Anthony R. Gregg (2017)
Mitochondria and reproduction: possibilities for testing and treatment.
Stine Gry Kristensen (2019)
Mitochondrial Disease: Advances in Clinical Diagnosis, Management, Therapeutic Development, and Preventative Strategies
C. Muraresku (2018)
Recent developments in genetic/genomic medicine
R. Horton (2019)
Pathogenic Mitochondria DNA Mutations: Current Detection Tools and Interventions
M. F. Mustafa (2020)
Genetics of Arterial-Wall-Specific Mechanisms in Atherosclerosis: Focus on Mitochondrial Mutations
A. Orekhov (2020)
Comparative analysis of different nuclear transfer techniques to prevent the transmission of mitochondrial DNA variants.
M. Tang (2019)
Three-parent babies: Mitochondrial replacement therapies
Hana Carolina Moreira Farnezi (2020)
Improvement of early developmental competence of postovulatory‐aged oocytes using metaphase II spindle injection in mice
T. Ogawa (2020)