Three-parent in vitro fertilization: Gene replacement for the prevention of inherited mitochondrial diseases

Paula Amato, Masahito Tachibana, Michelle Sparman, Shoukhrat Mitalipov

    Research output: Contribution to journalReview articlepeer-review

    74 Scopus citations


    The exchange of nuclear genetic material between oocytes and embryos offers a novel reproductive option for the prevention of inherited mitochondrial diseases. Mitochondrial dysfunction has been recognized as a significant cause of a number of serious multiorgan diseases. Tissues with a high metabolic demand, such as brain, heart, muscle, and central nervous system, are often affected. Mitochondrial disease can be due to mutations in mitochondrial DNA 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. Because mitochondrial DNA 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.

    Original languageEnglish (US)
    Pages (from-to)31-35
    Number of pages5
    JournalFertility and sterility
    Issue number1
    StatePublished - Jan 2014


    • Mitochondria
    • gene replacement
    • nuclear transfer

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Obstetrics and Gynecology

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