'Super puppies' created in DNA manipulation: Chinese mainland scientists turn genetic editing into reality

Removing an embryo from the womb, editing its genome and then reinserting the fetus back inside its mother may sound like a scene from a science-fiction movie.

But mainland scientists used this technique to breed a pair of so-called "super puppies" that can build muscle faster than their naturally bred peers.

This was the first time genome editing, a powerful tool that allows biologists to manipulate a person's or animal's DNA almost at will using molecular "scissors", has been performed on a mammal without the involvement of a surrogate mother to host the fertilised egg.

Details of the groundbreaking experiment - carried out by Professor Lai Xiangxue and his team in Guangzhou last year - is published in the latest Journal of Molecular Cell Biology.

Although the researchers stress they have no plans of using this technology on humans, the breakthrough has removed a major hurdle towards that by simplifying the process of genome editing and sidesteps the ethical complications related to having a surrogate host.

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In the future, such technology could be used to save children with defects from being aborted as such impairments could be "corrected" before they are born.

DNA testing can detect signs of a defect during the early stages of pregnancy, but no remedy is available once a problem is found. Parents have two choices: terminate the pregnancy or risk having a child with a potentially very severe physical or mental handicap.

Genome editing is seen in some quarters as the road forward in terms of meeting challenges like this. In the past, it has been applied to large mammals and used in genetic experiments on pigs, monkeys, cows and goats to cover a range of health issues. But editing an embryo is a painstaking process.

First, the researchers had to target the problematic gene, then they had to isolate and remove it. The next step involved waiting for the double-stranded structure of the subject's genome - which contains its complete set of DNA including all its genes - to re-grow in the "wounded" area.

During this process, the embryo had to be kept in an artificial environment. In most cases, a surrogate mother was required to accept the genetically modified embryo in place of the biological mother.

However, scientists were previously not able to edit the genome of dogs because their embryos died too quickly after leaving the mother's body.

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“That forced us to look for an alternative way to bypass the use of a surrogate [host],” said Zou Qingjian, a scientist involved in the study who works with the Chinese Academy of Sciences’ Guangzhou Institute of Biomedicine and Health in southern China.

“We tried to use traditional methods to grow the embryo in another womb nearly one hundred times but they all failed,” said Zou.

“We realised there must be something wrong, and that we should return the embryo to the biological mother.”

In their paper published in the Journal of Molecular Cell Biology, the team led by professor Lai Xiangxue detailed their groundbreaking work that led to the super puppies.

They “flushed” freshly fertilised eggs out of one oviduct of a pregnant Beagle, then removed a gene known to hinder muscle growth before reinserting the eggs inside the same animal - but in another oviduct.

The genetically modified embryos led to two healthy Beagles with superior musculature of other dogs the same age and breed. The two “super puppies” are now 15 months old.

“A major challenge of this technology is speed. We must finish editing the genome in less than half an hour, which requires [a lot of] practice,” Zou said.

The team based its approach on a popular way of editing genomes called CRISPR/Cas9. This edits the DNA by employing the same kind of natural cutting tool that a cell’s immune system uses to cut out areas infected with a virus.

The rapid advancement of genome editing technology in recent years enabled the Chinese team to remove unwanted genes relatively quickly.

Zou said this method will enable scientists around the world to study many gene-related diseases using canines.

“Dogs are a good animal model for scientists. They are much more similar to humans than mice are, and they grow faster than monkeys,” Zou said.

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“Removing the muscle-blocking gene is only the first step. Beagles are very smart, with a cardiovascular system very similar to that of a human’s. We will soon use them to study a wide range of important diseases including Parkinson’s, Alzheimer’s and heart diseases.”

Zou said their technology still has room for improvement, however.

In their experiment, for example, the whole litter had to be birthed at the same time and it took some time and effort for the researchers to identify which were the genetically modified puppies, he said.

“We are also considering using the same technology on other animals. No one has edited the genomes of a cat yet,” he added.

He warned that the technology was not yet ready to be applied to human embryos.

“We do not have a timetable for human use yet,” he said.

“The technology is still at a very early stage. If it is applied too hastily it could have unexpected consequences.”

With the aid of generous government funding, various teams of Chinese researchers have aggressively been pursuing the development and application of genome editing technology.

In April, another Chinese team reported that they had edited human embryos for the first time. Although they only used defective embryos from hospitals, the research still stirred controversy internationally due to the ethical implications of “playing God”.