Pioneering scientists edit genes in embryos to stop inherited diseases

Thursday, 03 Aug, 2017

Mitalipov's work, by contrast, involved human embryos that he and his team created with sperm donated by men who had the genetic mutation leading to the heart disease they were trying to edit out of the embryos.

A team of South Korean and US scientists has successfully edited the DNA in human embryos to correct a genetic defect causing incurable diseases.

The new study is a significant advancement from the first experiments on human embryos using CRISPR. California's Salk Institute for Biological Studies, China's Beijing Genomics Institute and South Korea's Seoul National University and Institute for Basic Science also contributed to the study.

Izpisua Belmonte and Wu emphasize that, although promising, these are very preliminary results and more research will need to be done to ensure no unintended effects occur.

USA teams at Oregon Health and Science University and the Salk Institute along with the Institute for Basic Science in South Korea focused on hypertrophic cardiomyopathy. The same tool could be used to cut out those faults for all of those, and eventually could be used to target cancer mutations.

The study used 75 human zygotes in which the father carried a mutation on the MYBPC3 gene, Belmonte said. At the same time, the eggs were injected with gene editing tools.

The researchers in this case got around it the old fashioned way: They used private money.

The goal was to correct a type of inherited heart condition.

Hypertrophic cardiomyopathy affects around one in 500 people and can result in sudden death.

The gene mutation in question causes a hereditary disease called hypertrophic cardiomyopathy which causes the wall of the heart muscle to become thickened.

The new CRISPR technique could be used to increase the number of viable embryos for implantation, said the team, thus reducing the number of eggs that have to be invasively harvested.

The researchers used sperm from a donor carrying the mutation, and eggs from healthy women.

The treatment replaces faulty inherited DNA in the mitochondria, tiny rod-like bodies in cells that supply energy, to prevent devastating diseases. These were sequenced and the researchers found that the editing had indeed worked. The most prominent expression of concern came in the form of a 2015 letter signed by CRISPR co-inventor Jennifer Doudna, Nobel laureate David Baltimore and 16 other prominent scientists.

Researchers in China were the first to reveal attempts to modify genes in human embryos using CRISPR.

Federal agencies also ban funding of research that ultimately leads to the destruction of human embryos in research.

"We definitely want to replicate this study with other mutations and other donors", said Amato.

In a report this year, a panel of the National Academy of Sciences addressed the potential and the risks of germline engineering, concluding that basic research should proceed, closely watched.

The study noted that further work was needed on genome editing processes before moving to clinical trials. "The other barrier is, the (US Food and Drug Administration) is prohibited from considering any clinical trials related to germline genetic modification", she said. Once the embryos were five days old, the team stopped their growth and checked to see how well their approach had wiped out the mutant gene. She said that while pre-implantation genetic screening of embryos is now available, it isn't ideal.

"The authors have made an important discovery regarding the fix of CRISPR-induced DNA breaks in human eggs just at the time of fertilization", he said.

The procedure was conducted on embryos created in the lab for the objective of testing the CRISPR-Cas9 treatment. The UK received a licence in 2016 to carry out CRISPR on human embryos for research into early development. They edited them using CRISPR-Cas9 to correct the mutation.

"If all of this holds up for different genes and is also true when the mutation is inherited from the mother, it will be a major step forward", said Janet Rossant, senior scientist and chief of research emeritus at the Hospital for Sick Children in Toronto.

After genome editing, the aim would be for 100% of embryos to be normal. Part of what makes this new work notable is that it avoided the pitfalls that afflicted those studies, such as off-target edits, in which CRISPR-Cas homes in on a similar, but wrong, gene, and mosaicism, in which embryos contain both edited and unedited cells. This is a dominant disease, so an affected individual only needs one abnormal copy of the gene to be affected. They seem to have a knack when it comes to manipulating embryos.