Gene-editing breakthrough could spell end of hereditary disease

Mitalipov is director of the Center for Embryonic Cell and Gene Therapy at OHSU.

Illustration of a human embryo.

The researchers concentrated on hypertrophic cardiomyopathy (HCM) a heart muscle disease that affects about 1 in 500 people and can result in sudden death.

The technique already has been used in animals for generating mutant models. He also wanted to explore the possibility of targeting cancer mutations, such as the BRCA1 and 2 gene defects that cause inherited breast cancer.

In theory, the genes could be corrected, preventing generations of women from developing cancer caused by those mutations. In the US, Congress has barred the Food and Drug Administration from even considering human trials with edited embryos, while in the United Kingdom it is illegal to implant genetically modified embryos in women.

The genome editing tool used, CRISPR-Cas9, has transformed the field of biology in the short time since its discovery in that it not only promises, but delivers.

In a series of laboratory experiments reported in the journal Nature, the OR researchers tried a different approach.

The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond the academic appointment above. “So there is still a long road ahead, particularly if you want to do it in a regulatory way”.

Mitalipov’s team targeted a genetic mutation that causes a potentially fatal cardiovascular condition known as hypertrophic cardiomyopathy. It’s well known among cardiologists for killing young athletes.

Reflecting the combination of fear and wonder represented by the development, one of the researchers said: “We are finally starting to address disease-causing mutations that impact potentially millions of people” – before highlighting the dangers of taking this breakthrough in technology to its logical conclusion of creating the “perfect” offspring.

Then they used the man’s sperm to fertilize eggs from 12 female donors – injecting CRISPR at the same time.

We all inherit two copies of each gene, one from dad and one from mom – and those embryos just copied the healthy one from the donated egg.

The embryos were editing using a powerful gene-editing tool called Crispr-Cas9, which works by precisely snipping away the defective piece of DNA from embryos containing the mutation.

“It was easy”, Mitalipov said. It is good because it suggests that embryos will often perform high-quality repairs without any extra prompting.

In more than half of the embryos, the DNA mutation was replaced with “healthy” DNA, and these embryos appeared to grow normally to the blastocyst stage (the point at which they would normally be transferred back into the woman’s uterus during the IVF process – in this study, the blastocysts were destroyed during analysis).

The embryos they modified were not allowed to develop for more than a few days and were not implanted in a womb. Some countries, especially in Europe, ban germline research. Thus some of the embryos carried the DNA error, and some were “healthy”. Embryos can be genetically screened before they are implanted during in vitro fertilization.

In the new study, just one embryo turned out a mosaic. “With this particular mutation, we’ve already done the groundwork, so we’re probably much closer to clinical applications”, Mitalipov said during a conference call with journalists. “I think it could be widely used if it’s proven safe”.

They also raise the ethical concerns worthy of a “brave new world” of Aldous Huxley.

“It is a very important study”, said Dr. Dusanka Babovic-Vuksanovic, genomics chair at Mayo Clinic in Rochester, Minnesota.

The scientists say their research held several surprises. “It’s the best way to treat the disease before the genetic mutation is actually transmitted to the embryo”.

“She has early onset dementia”, Urbina said. The CRISPR editing would essentially eliminate the mutation from that family’s pedigree.

“We need to see if this can be replicated and evaluate the safety”, said Wu.

“I’m so grateful that they dedicate their lives to this”, Urbina said. Harold and Leila Y. Mathers Charitable Foundation, the Moxie Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, and Shenzhen Municipal Government of China. It will be interesting to look out for the published results from the Oregon Health and Science University about their experimentation using CRISPR to alter genes in human embryos.

But in an interview with KPBS, a Salk scientist involved in the study said more scientific work and ethical consideration is needed before using this approach in the creation of any future human children.