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Twin Monkeys Born From Transplanted DNA Open Way To New Fertility Treatment That

Prevents Mothers Passing On Certain Inherited Diseases

http://www.medicalnewstoday.com/articles/162266.php

Twin monkeys born in a breakthrough experiment conducted in the US could open

the way to a new gene therapy that uses a fertility method called spindle

transfer to transplant DNA from one egg to another to prevent certain types of

inherited diseases passing from mother to offspring.

The twin monkeys called " Mito " and " Tracker " are the world's first animals to be

born after using spindle transfer. The breakthrough experiment was the work of

researchers at the Oregon Health & Science University's (OHSU) Oregon National

Primate Research Center (ONPRC), and is described in a paper that appeared

online the journal Nature on 26 August.

This successful result opens the way to a new type of fertility method that

could healp break the chain of several serious genetic diseases that are passed

from mothers to their offspring through mutated DNA in the mother's cell

mitochondria.

One of the authors, Dr Shoukhrat Mitalipov, told the media that:

" We believe this discovery in nonhuman primates can rapidly be translated into

human therapies aimed at preventing inherited disorders passed from mothers to

their children through the mitochondrial DNA, such as certain forms of cancer,

diabetes, infertility, myopathies and neurodegenerative diseases. "

Mitalipov, who is an associate scientist in the Division of Reproductive

Sciences at ONPRC, the Oregon Stem Cell Center and the departments of Obstetrics

and Gynecology and Molecular & Medical Genetics of Oregon Health & Science

University (OHSU), explained that:

" Currently there are 150 known diseases caused by mutations of the mitochondrial

DNA, and approximately 1 out of every 200 children is born with mitochondrial

mutations. "

Mitochondria are like little power plants inside each cell: they provide the

energy that the cell needs to grow and metabolize, and they also have their own

DNA that is separate from the DNA in the nucleus.

When sperm fertilizes an egg cell, the resulting embryo almost always inherits

its mitochondria from the egg, which carries only the mother's mitchondrial DNA,

and if she carries mitchondrial mutations that cause disease, then so will the

embryo.

For the study, Mitalipov and colleagues used a fertility method they developed

called spindle transfer, where they transfer the chromosomes of the mother

(leaving behind her mitochondrial DNA) into a healthy donated egg that has been

stripped of its chromosomes but not its healthy mitchondrial DNA.

The new egg is then fertilized and develops into an embryo made with the DNA of

the mother and the father, but without the mitchondrial DNA of the mother,

instead the it inherits the mitochondrial DNA of the donor of the egg.

In this case, the researchers implanted the fertilized monkey embryos into

surrogate mothers that went on to give birth to two healthy twin monkeys,

nicknamed " Mito " and " Tracker " , after the procedure that was used for imaging

the mitochondria.

(Note the monkeys were twins because the egg and sperm they were made from came

from the same parents although they were born to different surrogate mothers).

Follow up tests found little to no trace of cross-animal mitochondrial transfer,

showing that the experiment succeeding in keeping nuclear genetic material

separate from mitochondrial genetic material during the transfer.

Mitalipov said that in theory he and his colleagues had established that it was

possible to use this approach to help mothers carrying mitochondrial DNA

diseases from passing them onto their children.

" We believe that with the proper governmental approvals, our work can rapidly be

translated into clinical trials for humans, and, eventually, approved

therapies, " he added.

The Oregon National Primate Research Center, the Oregon Stem Cell Center; and

the National Center for Research Resources and the National Institute of Child

Health and Human Development, both components of the National Institutes of

Health, paid for the study.

" Mitochondrial gene replacement in primate offspring and embryonic stem cells. "

Masahito Tachibana, Sparman, Hathaitip Sritanaudomchai, Hong Ma,

Clepper, Joy Woodward, Ying Li, Ramsey, Olena Kolotushkina, Shoukhrat

Mitalipov.

Nature, 26 August 2009

DOI: 10.1038/nature08368

Source: OHSU Primate Center

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