Erschienen in:
19.07.2022 | Commentary
Operation “mitochondrial wipeout” — clearing recipient mitochondria DNA during the cytoplasmic replacement therapy
verfasst von:
Anastasia Kirillova, Ilya Mazunin
Erschienen in:
Journal of Assisted Reproduction and Genetics
|
Ausgabe 10/2022
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Excerpt
Human mitochondria contain a double-stranded circular DNA (mtDNA) that encodes information about the core structures of the oxidative phosphorylation complexes as well as the elements of machinery for translation of mtDNA genes. Pathogenic mtDNA mutations lead to various neuromuscular and neurodegenerative diseases with an estimated population prevalence of 1 in 200 [
1]. Mutations are generally in the state of heteroplasmy: Several allelic variants of mtDNA are present within the same cell or tissue. Clinical presentations of disorders associated with those mutations include stroke-like episodes, acquired ptosis and/or ophthalmoplegia, sideroblastic anemia, and epilepsy partialis continua [
2]. Treatments for mitochondrial diseases are currently focused on symptomatic management, although several experimental procedures are developing [
3]. The most promising experiments were performed by using site-specific nucleases targeting one of the mtDNA haplotypes [
4]. It is worth noting that the heteroplasmy shift was also used on oocytes as a part of assisted reproductive technologies (ART) in animals [
5]. However, it should be taken into consideration that the heteroplasmy shift might lead to decrease of embryonic developmental potential due to the lack of mtDNA as it is strictly down-regulated from the fertilized oocyte through the preimplantation embryo [
6]. …