Exclusive: Mice with human chromosomes - the genetic breakthrough that could revolutionise medicine

Scientists have created genetically-engineered mice with artificial human chromosomes in every cell of their bodies, as part of a series of studies showing that it may be possible to treat genetic diseases with a radically new form of gene therapy.

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In one of the unpublished studies, researchers made a human artificial chromosome in the laboratory from chemical building blocks rather than chipping away at an existing human chromosome, indicating the increasingly powerful technology behind the new field of synthetic biology.

The development comes as the Government announces today that it will invest tens of millions of pounds in synthetic biology research in Britain, including an international project to construct all the 16 individual chromosomes of the yeast fungus in order to produce the first synthetic organism with a complex genome.

A synthetic yeast with man-made chromosomes could eventually be used as a platform for making new kinds of biological materials, such as antibiotics or vaccines, while human artificial chromosomes could be used to introduce healthy copies of genes into the diseased organs or tissues of people with genetic illnesses, scientists said.

Researchers involved in the synthetic yeast project emphasised at a briefing in London earlier this week that there are no plans to build human chromosomes and create synthetic human cells in the same way as the artificial yeast project. A project to build human artificial chromosomes is unlikely to win ethical approval in the UK, they said.

However, researchers in the US and Japan are already well advanced in making “mini” human chromosomes called HACs (human artificial chromosomes), by either paring down an existing human chromosome or making them “de novo” in the lab from smaller chemical building blocks.

Natalay Kouprina of the US National Cancer Institute in Bethesda, Maryland, is part of the team that has successfully produced genetically engineered mice with an extra human artificial chromosome in their cells. It is the first time such an advanced form of a synthetic human chromosome made “from scratch” has been shown to work in an animal model, Dr Kouprina said.

“The purpose of developing the human artificial chromosome project is to create a shuttle vector for gene delivery into human cells to study gene function in human cells,” she told The Independent. “Potentially it has applications for gene therapy, for correction of gene deficiency in humans. It is known that there are lots of hereditary diseases due to the mutation of certain genes.”

Synthetic biology is loosely defined as designing new kinds of life-forms or making new genetic arrangements that do not exist in nature, which could provide practical benefits to society, notably in medicine, manufacturing or environmental monitoring.

At a speech to the Royal Society last November, the Chancellor George Osborne identified synthetic biology as one of eight areas of scientific development that the Government wants British scientists to focus on in the coming years.

David Willetts, the minister responsible for universities, will tell an international meeting on synthetic biology at Imperial College London today that the Government will spend more than £60m on synthetic biology, including £10m on a new innovation centre to translate academic research into industrial processes and products, and £1m on the international synthetic yeast project.

“Synthetic biology has huge potential. Indeed it has been said that it will heal us, feed us and fuel us. The UK can be world-leading in this emerging technology,” Mr Willetts said.

“Synthetic biology has huge potential for our economy and society in so many areas, from life sciences to agriculture. But to realise this potential we need to ensure researchers and businesses work together.”

Dr Kouprina said that human artificial chromosomes are sometimes known as “chromosome 47” because the normal complement of chromosomes in human cells is 46. One great advantage in gene therapy is that the 47th chromosome does not interfere with the other 46 chromosomes, unlike conventional gene therapy where an extra gene is inserted often at random into the human genome, she said.

“Conventional gene therapy uses vectors such as viruses to insert genes into chromosomes, but this can cause problems which do not happen with human artificial chromosomes because they do not interfere with other parts of the genome,” Dr Kouprina said.

“The idea is to take skin cells from a patient, turn them into stem cells and insert HACs into these stem cells with healthy copies of the disease gene. These cells, with the extra chromosome, can then be inserted back into the patient to treat the illness.”

She continued: “Clearly there is a long way to go before we can use HACs as vectors for treating genetic disease. However, the potential is there and this is an exciting area for scientific exploration with great potential benefits.”

Paul Freemont of Imperial College, one of the leaders of the synthetic yeast project, said that human artificial chromosomes produced by scientists such as Dr Kouprina are much smaller than natural human chromosomes and do not constitute the kind of synthetic chromosome planned for the yeast project.

“There is a big difference between moving bits of chromosomes around, as for gene therapy, and the full and complete chemical synthesis of a human chromosome. Such a project could involve design at a level that is not possible using standard molecular biology techniques,” he said.

“As far as I know no one is chemically synthesising a full refactored human chromosome. If we were to propose this at Imperial we would have to get ethical approval.”

The project to build 16 artificial yeast chromosomes and insert them into an empty yeast cell would break new ground. It would be the first time a synthetic “eukaryote” organism – with a complex genome composed of chromosomes as opposed to the simple strings of genes in “prokaryote” bacteria – would be constructed in the laboratory.

Yeasts have been used for thousands of years to make bread and beer, Dr Freemont said. “Now we have the opportunity to adapt yeasts further, turning them into predictable and robust hosts for manufacturing the complex products we need for modern living,” he said.

The scientists said that they expect the first synthetic yeast to be made with a full complement of 16 artificial chromosomes and 6,000 genes by 2018. The UK will build chromosome number 11, composed of about 700,000 base pairs of DNA.

Synthetic biology: A 60-year revolution

1953: American biologist James Watson and English physicist Francis Crick, below, working together in Cambridge, reveal the double helix structure of DNA, with help from Maurice Wilkins and Rosalind Franklin of Kings College London. The field of DNA science is born.

1973: Stanley Cohen and Herbert Boyer in the United States create the technique of DNA cloning, allowing genes to be transplanted between different biological species. Using restriction enzymes to cut DNA into fragments and plasmids for cloning DNA strands, the technology of genetic engineering was born.

1982: First transgenic animal – a mouse – is created by transferring the gene from one animal into the fertilised eggs of another. All subsequent generations of the transgenic mouse carried the extra gene.

1983: Biochemist Kary Mullis creates the polymerase chain reaction. This enables scientists to amplify tiny fragments of DNA to almost unlimited quantities. It becomes a valuable technology for gene manipulation.

1983: First genetically modified plant is created, a tobacco plant resistant to an antibiotic. This was to lead to the unleashing of millions of hectares of GM crops from Brazil to China.

1983: Mice with human genes created. These transgenic mice became basis of animal models for human diseases.

2003: Mapping of the human genome completed, giving the full genetic blueprint of some 23,000 genes, the digital recipe for Homo sapiens.

2008: Craig Venter announces first synthetic organism, a bacteria called ‘Mycoplasma laboratorium’ or “Synthia”, controlled by a single, completely synthetic chromosome.

2013: International project announced to produce synthetic yeast cell with 16 man-made chromosomes.