Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases.
Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases.
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DOI：
10.1016/j.fertnstert.2013.11.030
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发表时间：
2014-01
影响因子：
6.7
通讯作者：
Mitalipov S
中科院分区：
文献类型：
--
作者：
Amato P;Tachibana M;Sparman M;Mitalipov S
Mitochondrial dysfunction has been recognized as a significant cause of a number of serious multi-organ diseases. Tissues with a high metabolic demand such as brain, heart, muscle, CNS are often affected. Mitochondrial disease can be due to mutations in mitochondrial DNA (mtDNA) or in nuclear genes involved in mitochondrial function. There is no curative treatment for patients with mitochondrial disease. Given the lack of treatments and the limitations of prenatal and preimplantation diagnosis, attention has focused on prevention of transmission of mitochondrial disease through germline gene replacement therapy. Since mtDNA is strictly maternally inherited, two approaches have been proposed. In the first, the nuclear genome from the pronuclear stage zygote of an affected woman is transferred to an enucleated donor zygote. A second technique involves transfer of the metaphase II spindle from the unfertilized oocyte of an affected woman to an enucleated donor oocyte. Our group recently reported successful spindle transfer between human oocytes resulting in blastocyst development and embryonic stem cell derivation, with very low levels of heteroplasmy. In this review, we summarize these novel assisted reproductive techniques and their use to prevent transmission of mitochondrial disorders. The promises and challenges are discussed, focusing on their potential clinical application.
