CRISPR used to edit out sudden-death gene mutations in major first

3 Aug 2017

Scientist removing the egg shell from a zebrafish embryo under a stereo microscope. Image: Micha Weber/Shutterstock

CRISPR’s original promise appears to be coming to fruition after a potentially fatal hereditary gene was edited out of an embryo.

CRISPR – or CRISPR-Cas9, to give it its full name – is heralded as an advanced technique that could change the course of medicine by allowing researchers to cut out genetic mutations in embryos that contribute to hereditary conditions.

One of the first steps to this becoming a reality has taken place, with help from a team of international researchers that, for the first time, used CRISPR to correct a mutation that leads to heart conditions in future generations.

Future Human

In a paper published to Nature, the team revealed that it used the technique on embryos in their earliest stage of development to cut out the genes that lead to the formation of hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in athletes and young people.

Affecting approximately 1 in 500 people, the condition is caused by a dominant mutation in the MYBPC3 gene. Those with the faulty gene have a 50pc chance of passing it on to their children.

How they did it

To achieve this major breakthrough, the researchers generated stem cells from a skin biopsy from a person with HCM and, using CRISPR, specifically targeted the MYBPC3 gene for repair.

The donor’s own stem cells were then inserted in place of the mutation during the next round of cell division, by using either a synthetic DNA sequence or the non-mutated copy of the MYBPC3 gene as a template.

Using IVF techniques, the researchers injected the best-performing gene-editing components into healthy donor eggs, newly fertilised with the donor’s sperm.

To their surprise, analysis of the repair work was found to be both very safe and efficient. A high percentage of the embryonic cells were repaired, and it did not induce any unintended mutations in other genes.

This might allay of reports on CRISPR over the past few months, which showed examples of the technique mutating other genes unrelated to experiments, suggesting it could lead to more damage than good.

Proceed with caution

“Thanks to advances in stem cell technologies and gene editing, we are finally starting to address disease-causing mutations that impact potentially millions of people,” said Juan Carlos Izpisua Belmonte, a professor from the Salk Institute and one of the authors of the paper.

“Gene editing is still in its infancy so even though this preliminary effort was found to be safe and effective, it is crucial that we continue to proceed with the utmost caution, paying the highest attention to ethical considerations.”

The team stressed, however, that these are still very preliminary results and more research will need to be done to ensure no unintended effects occur.

This latest news comes just days after a team in the US announced it had changed the DNA of “a large number of one-cell embryos”, paving the way for a process to correct defective genes that cause inherited diseases.

Colm Gorey was a senior journalist with Silicon Republic