Spindle transfer

For other uses, see Spindle (disambiguation).

A spindle transfer (more properly "spindle-chromosomal complex transfer") is a genetic manipulation technique where the donor's nuclear DNA but not her mitochondrial DNA is transferred to the receiving egg. It may be used to treat mitochondrial diseases.

History

Polarized light microscopy spindle imaging and manipulation first were reported (Nature Biotechnology 2000;18(2)223-5) by a team then at the Woods Hole Marine Biological Laboratory and Women & Infants Hospital of Rhode Island's Division of Reproductive Medicine and IVF.[1] They reported 100% spindle enucleation efficiency with transfer of few mitochondria in the karyoplasts of oocytes from various mammalian species. In an article published in Nature online on August 26, 2009, a team in Oregon headed by Shoukhrat Mitalipov made the report of the birth several rhesus macaque offspring born with donor mitochondria following spindle transfer.[2] This has the implication that any genetic problems which may be transferred from mother to offspring through mitochondrial DNA can be avoided.[3] Teams from the Oregon National Primate Research Center at the Oregon Health & Science University (OHSU) were all credited in the study.

The 2009 experiment was extended and in a 2012 study[4] the offspring were reported as being alive and well at the age of three years, and the team also conducted experimenst using human eggs and produced embryos and embryonic stem cells. Shoukhrat Mitalipov, a developmental biologist at OHSU, and his team retrieved more than 100 eggs from seven women volunteers, who ranged in age from 21 years to 32 years. Of these eggs, 65 were used in the spindle-transfer experiment, while 33 served as non-manipulated controls. Both groups were fertilized by sperm in a lab dish, and their fertilization rate was shown to be roughly the same at more than 70%.[5]

In September 2016, John Zhang and his team of researchers at the New Hope Fertility Center in New York City were reported to have conducted the spindle transfer mitochondrial donation procedure in Mexico for a Jordanian couple where the wife had Leigh disease. A baby boy was born to the mother in April 2016.[6][7]

Procedure

The technique involves taking nuclear DNA from an egg cell and transferring that DNA into another egg cell, leaving the defective mitochondrial DNA behind. The cell is then implanted using in-vitro fertilization techniques. The final mitochondrial DNA, however, is from the receiving egg cell, causing the original donor's mitochondrial DNA to not be passed on to the eventual offspring.

Genetic analysis may then be utilized to confirm that the mother's mitochondrial DNA is not part of the final DNA makeup.

Macaca mulatta monkeys were used in recent experiments.

Implications

The implications is that a mother who has one of the 150 or so documented syndromes or diseases due to a mitochondral DNA aberration would be able to, using this technique, have children without the mitochondrial issues. In the 1990s a different procedure called cytoplasmic transfer was used on a small scale to allow infertile women with genetic defects in their mitochondria to have children but this procedure fell out of favour.[7][8]

See also

References

  1. ↑ Liu, Lin; et al. (2000). "A reliable, noninvasive technique for spindle imaging and enucleation of mammalian oocytes". Nature Biology. 18: 223–225. doi:10.1038/72692. Retrieved 2 March 2016.
  2. ↑ Masahito Tachibana, M; Michelle Sparman; Hathaitip Sritanaudomchai; Hong Ma; Lisa Clepper; Joy Woodward; Ying Li; Cathy Ramsey; Olena Kolotushkina; Shoukhrat Mitalipov (17 September 2009). "Mitochondrial gene replacement in primate offspring and embryonic stem cells". Nature. 461 (7262): 367–372. doi:10.1038/nature08368. PMC 2774772Freely accessible. PMID 19710649.
  3. ↑ Paddock, Catherine (28 August 2009). "Twin Monkeys Born From Transplanted DNA Open Way To New Fertility Treatment That Prevents Mothers Passing On Certain Inherited Diseases". Medical News Today.
  4. ↑ Tachibana, Masahito; et al. (24 October 2012). "Towards germline gene therapy of inherited mitochondrial dieases". Nature. 493: 627–631. doi:10.1038/nature11647. Retrieved 2 March 2016.
  5. ↑ Naik, Gautam (24 October 2012). "DNA Switch Shows Promise Against Genetic Disease". Wall Street Journal. Retrieved 27 November 2012.
  6. ↑ Roberts, Michelle (2016-09-27). "First 'three person baby' born using new method". BBC News. Retrieved 2016-10-01.
  7. 1 2 Hamzelou, Jessica (2016-09-28). "Everything you wanted to know about '3-parent' babies". The New Scientist. Retrieved 2016-10-01.
  8. ↑ "Genetically altered babies born". BBC News. 2001-05-04. Retrieved 2008-04-26.
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