Precision medicine has defined future of 21st century medicine – from activating dormant genes to arming genetically-modified cells to target cancer cells, it aims to treat previously incurable diseases.

As such, it is no surprise that research and investment on precision medicine continues to gain rapid traction annually with scientists aiming to outdo one another. Now, a team of Chinese researchers have been able to carry out precise “chemical surgery” to repair mutations in human embryos.

A proof of concept

The team at Sun-Yat Sen University utilised a technique called base editing to correct targeted errors out of billions of base pair in the genetic code. By artificially editing one of the four fundamental building blocks of DNA – adenine, cytosine, guanine and thymine – the team corrected point mutations by replacing the aberrant base pair with a correct one.

The breakthrough was that the team corrected the gene mutations in embryos and as a proof of concept, the team altered lab-made embryos to remove the disease beta-thalassemia.

By identifying the aberrant code, known as a point mutation, the team were able replace the erroneous guanine with adenosine. Thus, correcting the sequence and, in theory, removing the beta-thalassemia genetic trait.

Junjiu Huang, one of the researchers, mentioned, "We are the first to demonstrate the feasibility of curing genetic disease in human embryos by base editor system."

Nevertheless, the procedure remains purely on a conceptual basis as the embryos were never implanted. All experiments were performed using tissue taken from patients with beta-thalassemia and human embryos made through cloning.

Possibility of clinical use in the future

Base editing itself is nothing new – being a more advanced form of gene-editing known as CRISPR. Rather than breaking down the DNA and inserting new genetic information (in CRISPR), base editing works on the DNA bases themselves to convert and correct into the correct sequence.

Pioneer of the base editing technique, Professor David Liu at Harvard University, has described base editing as “chemical surgery” and as a safer, more efficient technique compared to CRISPR. Professor Liu went on to point out the viability of base editing, "About two-thirds of known human genetic variants associated with disease are point mutations. So, base editing has the potential to directly correct, or reproduce for research purposes, many pathogenic [mutations]."

Commenting on the Chinese team’s work, Professor Liu mentioned that it was “interesting work” that demonstrates base editing's ability to "directly correct a pathogenic beta-thalassemia mutation in the promoter of the beta-thalassemia gene in cells from beta-thalassemia patients, and in cloned human embryos derived from these patient [skin] cells."

Addressing ethical issues more important than scientific viability

But, for base editing to succeed, its biggest hurdles lie in ethical approval rather than scientific viability.

Professor Robin Lovell-Badge, from the Francis Crick Institute in London, pointed out the lack of animal research before jumping straight into human embryos. Furthermore, the standards for human embryo research is not standardized worldwide with some countries having more lax regulations compared to others.

Speaking on the viability of base editing, Professor Lovell-Badge added, "There would need to be far more debate, covering the ethics, and how these approaches should be regulated… And in many countries, including China, there needs to be more robust mechanisms established for regulation, oversight, and long-term follow-up."

As such, he believes that base editing on human embryos are unlikely to be utilised clinically anytime soon.

With the deep ethical and societal debate behind a method like base editing, even the researchers at Sun-Yat Sen University are aware of the widespread reaches of their work. The team has even openly admitted that their new technique is nowhere near ready for being used clinically.

However currently, it is a proof of concept, one that “demonstrated the feasibility of curing genetic disease in human...embryos by base editor system." MIMS

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