Cloning technique that fixes mitochondrial genes could treat genetic diseases

U.S. researchers have used a controversial cloning technique to make new, healthy, perfectly matched stem cells from the skin of patients with mitochondrial diseases in a first step toward treatment for these incurable, life-threatening conditions.

A study on the technique, published in the journal Nature, showcases the latest advance in the use of somatic-cell nuclear transfer to make patient-specific stem cells that could be used to treat genetic diseases.

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"This work enables the generation of an unlimited and mutation-free supply of replacement cells for patients with mitochondrial disease," said Dr. Robert Lanza, Chief Scientific Officer at Advanced Cell Technology, who was not involved in the research.

Nuclear transfer is typically the first step in reproductive cloning using adult cells to make a genetic copy of an individual. Since the technique was first used in 1996 to create the cloned sheep Dolly, the United Nations has urged countries to ban it on ethical and moral grounds.

In 2013, Shoukhrat Mitalipov of Oregon Health and Science University was the first to succeed using the method to make human embryonic stem cells from a patient's skin cells. The cells are prized because they are "pluripotent," meaning they have the ability to transform into any type of cell in the body.

Replacements for diseased cells

In his latest study, Mitalipov and colleagues used the method to make replacement cells for patients with mutations in mitochondrial genes, which are critical for producing energy in cells. Mitochondrial genes have evaded scientists' efforts to correct such mutations, Mitalipov said.

For the study, the team removed the nucleus of patients' cells and implanted them into unfertilized human eggs in which the mitochondria remained, but the rest of the DNA was removed. They then coaxed the eggs into dividing, producing embryonic stem cells which could be used to make healthy heart or nerve stem cells to replace the patient's diseased cells.

The researchers also showed that they could produce healthy embryonic-like stem cells using another method in which they reprogram adult skin cells through the introduction of several genes, a method that does not involve the use of eggs.

Lanza said several clinical trials are underway globally testing pluripotent stem cell-derived therapies in humans, including treatments for diabetes, and eye and heart disease.

The work was funded by the Leducq Foundation, a private French foundation.