New gene-editing technique could prevent mitochondrial disease from being passed on

Chuck Bednar for redOrbit.com – @BednarChuck

A new gene-editing technique created by researchers at the Salk Institute for Biological Studies in California could provide new hope for women carrying a mitochondrial disease who want to be mothers, but are afraid of passing their condition on to their children.

Typically, these women have relied on preimplantation genetic diagnosis to pick the healthiest embryos, but as the researchers point out, this is no guarantee that they will have a healthy baby. The new technique, however, can simply and effectively eliminate these mitochondrial mutations from eggs and early-stage embryos using a pair of molecular “scissors.”

Understanding and treating mitochondrial disease

Mitochondrial diseases, which are passed exclusively from mother to child, result when these specialized cellular compartments responsible for creating most of the energy needed for a body to survive unexpectedly fail. The resulting reduction in energy causes injury and even death to the cells and eventually organs, ultimately causing entire systems to fail.

“Currently, there are no treatments for mitochondrial diseases,” explained Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory and senior author of a study on the new technique, published Thursday in the journal Cell. “Our technology may offer new hope for mitochondrial disease carriers wishing to have children without the disease.”

Each living cell can have up to thousands of mitochondria, and each of the organelles contains their own DNA which are vital for its function , the Salk Institute team explains. Mutations in this set of 37 genes can cause a wide array of different diseases, and can result in fatality at the time of birth, a short life expectance or several decades of debilitating symptoms.

A new approach: focusing on prevention, not cure

Alejandro Ocampo, a research associate in Izpisua Belmonte’s lab and one of the first authors of the paper, explained that most methods currently being used to address these hereditary illnesses focus on patients who have already contracted them. As an alternative, his team looked for ways to prevent the transmission of the mutations themselves early in a child’s development.

They focused on two types of molecules: restriction endonucleases and transcription activator-like effector nucleases (TALENs). They cut specific strands of DNA out of these nucleases and by doing so, were able to eliminate only the mitochondrial DNA that contained specific, disease-causing mutations in eggs or embryos while leaving healthy ones intact.

To prove their concept, they used mice containing two types of mitochondrial DNA, selectively prevented one of them from being passed on to their offspring by using engineered nucleases in both eggs and one-celled embryos. The mice born using this approach developed, as normal, into adults. Also, the authors were able to use the technique to successfully reduce levels of mutated mitochondrial DNA most responsible for a pair of human mitochondrial diseases.

“We might not be able to eliminate one hundred percent of the mutated copies of mitochondrial DNA, but you don’t need to eliminate all of the mutated copies: just reducing the percentage significantly enough can prevent the disease in the next generation,” said Pradeep Reddy, first author of the new paper and a research associate in the Izpisua Belmonte lab.

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