page_title: Mitochondrial replacement therapy
section_title: Techniques
hierarchical_section_title: Mitochondrial replacement therapy / Techniques
caption_attribution_description: The process of fertilization in the ovum of a mouse. (After Sobotta.)
context_page_description: Mitochondrial replacement therapy is the replacement of mitochondria in one or more cells to prevent or ameliorate disease. MRT originated as a special form of in vitro fertilisation in which some or all of the future baby's mitochondrial DNA comes from a third party. This technique is used in cases when mothers carry genes for mitochondrial diseases. The therapy is approved for use in the United Kingdom. A second application is to use autologous mitochondria to replace mitochondria in damaged tissue to restore the tissue to a functional state. This has been used in clinical research in the United States to treat cardiac-compromised newborns.
context_section_description: In in vitro fertilization and involves removing eggs from a woman, removing sperm from a man, fertilizing the egg with the sperm, allowing the fertilized egg to form a blastocyst, and then implanting the blastocyst. MRT involves an additional egg from a third person, and manipulating both the recipient egg and the donor egg.
  As of 2016 there were three MRT techniques: maternal spindle transfer (MST), pronuclear transfer (PNT), and more recently as of that date, polar body transfer (PBT). The original technique, in which cytoplasm taken from a donor egg and containing mitochondria, is simply injected into the recipient egg, is no longer used.
  In MST, an oocyte is removed from the recipient, and when it is in the metaphase II stage of cell division, the spindle-chromosome complex is removed; some of cytoplasm comes with it, so some mitochondria are likely included. The spindle-chromosome complex is inserted into a donor oocyte from which the nucleus has already been removed. This egg is fertilized with sperm, and allowed to form a blastocyst, which can then be investigated with preimplantation genetic diagnosis to check for mitochondrial mutations, prior to being implanted in the recipient's uterus.
  In pronuclear transfer, an oocyte is removed from the recipient, and fertilized with sperm. The donor oocyte is fertilized with sperm from the same person. The male and female pronuclei are removed from each fertilized egg prior to their fusing, and the pronuclei from the recipient's fertilized egg are inserted into the fertilized egg from the donor. As with MST, a small amount of cytoplasm from the donor egg may be transferred, and as with MST, the fertilized egg is allowed to form a blastocyst, which can then be investigated with preimplantation genetic diagnosis to check for mitochondrial mutations, prior to being implanted in the recipient's uterus.
  In polar body transfer, a polar body (a small cell with very little cytoplasm that is created when an egg cell divides) from the recipient is used in its entirety, instead of using nuclear material extracted from the recipient's normal egg; this can be used in either MST or PNT. This technique was first published in 2014 and as of 2015 it had not been consistently replicated, but is considered promising as there is a greatly reduced chance for transmitting mitochondria from the recipient because polar bodies contain very few mitochondria, and it does not involve extracting material from the recipient's egg.
caption: The process of fertilization in the ovum of a mouse, showing pronuclei.
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