Lab-grown genomes set to transform human DNA

Scientists in the UK have taken the first steps in a new programme to create whole human genomes from laboratory chemicals, which they say could eventually transform biology and medicine.

It will allow human DNA to be altered on a scale that is not possible with the more limited gene-editing techniques available today, and could be used for many applications such as making human cells resistant to viruses or altering the immune system.

The £10mn Synthetic Human Genome Project, funded by the Wellcome Trust, has successfully demonstrated that a synthetic chromosome can be transferred to a human cell.

It is a “landmark step for synthetic biology”, said James Collins, professor of medical engineering at Massachusetts Institute of Technology, who is not involved in the project. “This work lays essential groundwork for the engineering of synthetic human genomes and the transformative applications that will follow.”

The research strategy, described in the journal Science, involves first assembling a synthetic human chromosome — the DNA structure carrying genetic information — inside a mouse cell.

The synthetic chromosome is then transferred into a human cell in place of one of the original chromosomes. The nucleus of a human cell contains 23 chromosome pairs with one set inherited from each parent.

Programme leader Jason Chin of the Ellison Institute of Technology in Oxford and colleagues at the MRC Laboratory of Molecular Biology in Cambridge have previously pioneered the creation of microbes with synthetic genomes to make new materials that natural bacteria cannot produce.

But building a human genome requires a different strategy, said Chin. “It is 1,000 times larger than a bacterial genome — and a human cell contains two copies of each chromosome, so it is hard to engineer the DNA in one copy without affecting the other one,” he said.

To do this, the team uses a mouse embryonic stem cell as the “assembly cell” in which a human chromosome is engineered, he explained. “We are moving chunks of synthetic DNA to replace the corresponding chunks on the human chromosome inside the assembly cell.”

The experiments showed that the synthetic chromosome could be transferred to a human cell to replace one of the two natural chromosomes without causing damage. The whole process can be repeated and the second natural chromosome expelled to produce a human cell with two synthetic chromosomes.

Several years of development and safety evaluation will be required before the technology is ready to use in medicine. One possible application is to make human cells resistant to viruses, such as by repopulating the liver of immunocompromised patients to prevent them picking up infections, said Chin. “Another is to make cells with synthetic genomes precisely tailored for a particular type of cellular therapy.”

In the more immediate future, the synthetics genomics programme will provide new biological insights, Chin said. For example, the experiments have already shown that the DNA caps on the end of a human chromosome called telomeres grow up to 10 times longer when it is transferred to a mouse cell and then shrink back to their original size when put back into a human cell.

Although the Synthetic Human Genome programme does not envisage any outlandish experiments to transform human DNA for purposes that people might find objectionable, such as enhancing intelligence or physical appearance, it has set up a wide-ranging project with the University of Kent to examine the ethical, social, economic and policy implications of genome synthesis.

Illustrations by Ian Bott