Mitochondrial replacement therapy and the “three parent baby”

Abstract

The mitochondria contained in eukaryotic cells have their own DNA, and heritable mutations in mitochondrial DNA (mtDNA) can cause a variety of disorders in humans. A new therapy, mitochondrial replacement therapy (MRT), is currently being developed to address these mitochondrial disorders by eliminating the mutated mtDNA from the germline. The two main MRT techniques are pronuclear transfer, conducted in the zygote after fertilization, and spindle-chromosomal complex transfer, conducted in the oocyte before fertilization. In pronuclear transfer, the pronuclei from a zygote affected by a mtDNA mutation are transferred to an enucleated normal zygote. In spindle-chromosomal complex transfer, the genetic material from an oocyte affected by a mtDNA mutation is inserted into the cytoplasm of a donor oocyte that contains healthy mitochondria. A third method, polar body genome transfer, attempts to increase the efficiency of the above techniques by using polar bodies to supply the genetic material. While MRT is legally and ethically controversial, it has recently been implemented successfully in a clinical setting.