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Review
. 2011 Oct 15;20(R2):R168-74.
doi: 10.1093/hmg/ddr373. Epub 2011 Aug 18.

Mitochondrial DNA disease: new options for prevention

Lyndsey Craven  1 , Joanna L Elson, Laura Irving, Helen A Tuppen, Lisa M Lister, Gareth D Greggains, Samantha Byerley, Alison P Murdoch, Mary Herbert, Doug Turnbull
Affiliations
Review

Mitochondrial DNA disease: new options for prevention

Lyndsey Craven et al. Hum Mol Genet. .

Abstract

Very recently, two papers have presented intriguing data suggesting that prevention of transmission of human mitochondrial DNA (mtDNA) disease is possible. [Craven, L., Tuppen, H.A., Greggains, G.D., Harbottle, S.J., Murphy, J.L., Cree, L.M., Murdoch, A.P., Chinnery, P.F., Taylor, R.W., Lightowlers, R.N. et al. (2010) Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature, 465, 82-85. Tachibana, M., Sparman, M., Sritanaudomchai, H., Ma, H., Clepper, L., Woodward, J., Li, Y., Ramsey, C., Kolotushkina, O. and Mitalipov, S. (2009) Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature, 461, 367-372.] These recent advances raise hopes for families with mtDNA disease; however, the successful translational of these techniques to clinical practice will require further research to test for safety and to maximize efficacy. Furthermore, in the UK, amendment to the current legislation will be required. Here, we discuss the clinical and scientific background, studies we believe are important to establish safety and efficacy of the techniques and some of the potential concerns about the use of these approaches.

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Figures

Figure 1.
Figure 1.
Nuclear transfer techniques to prevent transmission of mtDNA disease. (A) Pronuclear transfer technique using a mitochondrial donor zygote. (B) Metaphase II spindle transfer technique using a mitochondrial donor oocyte followed by intracytoplasmic sperm injection fertilization. Both techniques will involve monitoring embryo development following transfer.
Figure 2.
Figure 2.
Pronuclei removal from an abnormally fertilized human embryo and transfer to an enucleated abnormally fertilized human embryo. (A) The tripronucleate human embryo (two pronuclei can be seen, arrowheads). A hole has been made in the zona pellucida using a microsurgical laser (arrow). (B) The biopsy pipette is inserted into the embryo and a pronucleus aspirated within a karyoplast (arrowhead). (C) The pronuclear karyoplast can be seen within the biopsy pipette (arrowhead). (D) A single pronuclear karyoplast removed from the embryo. (E) The pronuclear karyoplasts can be seen within the biopsy pipette (arrowheads). (F) The biopsy pipette is inserted through the hole in the zona pellucida. (G) The pronuclear karyoplasts are transferred into the enucleated embryo along with a small amount of HVJ-E. (H) The pronuclear karyoplasts (arrowheads) are allowed to fuse with the enucleated embryo.
See this image and copyright information in PMC

References

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