CRISPR fixes disease gene in viable human embryos

A team of scientists led by Shoukhrat Mitalipov at Oregon Health and Science University announced this week that they used a technology known as CRISPR to edit sections of the human genome, performing the procedure on embryonic humans.


Using the cutting-edge genome-editing technique CRISPR-Cas9 on multiple embryos, the researchers corrected a gene known to cause a type of heart disease called hypertrophic cardiomyopathy that can cause sudden cardiac arrest.

The team’s successful use of the CRISPR “gene editing” tool in viable embryos was hailed as a technical feat by outside experts, who called at the same time for deeper debate on the ethics of altering human DNA. That future might be a step closer now, thanks to a pre-clinical trial that has successfully repaired a disease-causing mutation in a human embryo, which would prevent that gene from being passed down to future generations. Work with skin cells reprogrammed to mimic embryos had suggested the mutation would be repaired in fewer than 30 percent of cells. Three separate studies were published in scientific journals describing Chinese experiments on gene editing in human embryos. The clinical trials can now move forward.

The edited embryos developed similarly to the control embryos, with 50 percent reaching the blastocyst stage, indicating gene editing does not block development, according to the researchers. In 2013, Mitalipov and his colleagues reported the first success in cloning human stem cells, reprogramming human skin cells back to their embryonic state.

We sought to investigate human gamete and embryo DNA fix mechanisms activated in response to CRISPR-Cas9-induced DSBs. “There is still work to do to improve the efficiency”, says Mitalopov. MYBPC3 mutations account for approximately 40% of all genetic defects causing HCM and are also responsible for a large fraction of other inherited cardiomyopathies, including dilated cardiomyopathy and left ventricular non-compaction6.

Then again, the gene-editing tool could be used to eliminate horrific, costly diseases like cystic fibrosis, sickle cell anemia, certain cancers and heart diseases, and perhaps even offer protection against Alzheimer’s. The second study, published in 2016, edited a gene to confer HIV resistance to the embryo.

“It may be that some countries never permit germline genome editing because of moral and ethical concerns”, said Professor Joyce Harper from University College London. In the report, he said, the scientists point out that this kind of gene editing is controversial “precisely because the resulting genetic changes would be inherited by the next generation, and the technology therefore would cross a line many have viewed as ethically inviolable”.

Once the gene was removed, the embryo’s own fix systems replaced them with the healthy version.

Similarly, Anna Middleton, vice chair of the United Kingdom association of genetic nurses and counselors, said while the science is “really elegant” it must be replicated extensively before any firm conclusions can be drawn about the accuracy and safety of the approach.

“We are going to do everything possible to bring (the research) safely to clinics”, Mitalipov said. Genes in which dominant mutations manifest as late-onset adult disorders include BRCA1 and BRCA2, which are associated with a high risk of breast and ovarian cancers1, and MYBPC3, mutation of which causes hypertrophic cardiomyopathy (HCM) 2. The work was consistent with recommendations issued this year by the National Academy of Sciences and the National Academy of Medicine joint panel on human genome editing. “There is still a long road ahead particularly if you want to do it in a really regulated way”. That would mean implanting the gene-edited embryo into a woman, and studying the genetically engineered child. If the affected embryos were implanted into women and carried to term, the resulting children would inherit the heart condition.


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. While the US has uniquely lax laws surrounding human genome editing (the government will not fund it, but private funders abound), over 40 countries have laws prohibiting germline gene editing – the kind that can be passed on to future generations – and all European countries are bound by the Convention on Human Rights and Biomedicine, which prohibit the same thing.

Splice with caution