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World’s first living organism with fully redesigned DNA created

BY IAN SAMPLE
THE GUARDIAN

Scientists have created the world’s first living organism that has a fully synthetic and radically altered DNA code.

The lab-made microbe, a strain of bacteria that is normally found in soil and the human gut, is similar to its natural cousins but survives on a smaller set of genetic instructions.

The bug’s existence proves life can exist with a restricted genetic code and paves the way for organisms whose biological machinery is commandeered to make drugs and useful materials, or to add new features such as virus resistance.

In a two-year effort, researchers at the Medical Research Council’s Laboratory of Molecular Biology in Cambridge read and redesigned the DNA of the bacterium Escherichia coli (E coli), before creating cells with a synthetic version of the altered genome.

The artificial genome holds 4m base pairs, the units of the genetic code spelled out by the letters G, A, T and C. Printed in full on A4 sheets, it runs to 970 pages, making the genome the largest by far that scientists have ever built.

“It was completely unclear whether it was possible to make a genome this large and whether it was possible to change it so much,” said Jason Chin, an expert in synthetic biology who led the project.

The DNA coiled up inside a cell holds the instructions it needs to function. When the cell needs more protein to grow, for example, it reads the DNA that encodes the right protein. The DNA letters are read in trios called codons, such as TCG and TCA.

Nearly all life, from jellyfish to humans, uses 64 codons. But many of them do the same job. In total, 61 codons make 20 natural amino acids, which can be strung together like beads on a string to build any protein in nature. Three more codons are in effect stop signs: they tell the cell when the protein is done, like the full stop marking the end of this sentence.

The Cambridge team set out to redesign the E coli genome by removing some of its superfluous codons. Working on a computer, the scientists went through the bug’s DNA. Whenever they came across TCG, a codon that makes an amino acid called serine, they rewrote it as AGC, which does the same job. They replaced two more codons in a similar way.

More than 18,000 edits later, the scientists had removed every occurrence of the three codons from the bug’s genome. The redesigned genetic code was then chemically synthesised and, piece by piece, added to E coli where it replaced the organism’s natural genome. The result, reported in Nature, is a microbe with a completely synthetic and radically altered DNA code. Known as Syn61, the bug is a little longer than normal, and grows more slowly, but survives nonetheless.

“It’s pretty amazing,” said Chin. When the bug was created, shortly before Christmas, the research team had a photo taken in the lab with a plate of the microbes as the central figure in a recreation of the nativity.

Such designer lifeforms could come in handy, Chin believes. Because their DNA is different, invading viruses will struggle to spread inside them, making them in effect virus-resistant. That could bring benefits. E coli is already used by the biopharmaceutical industry to make insulin for diabetes and other medical compounds for cancer, multiple sclerosis, heart attacks and eye disease, but entire production runs can be spoiled when bacterial cultures are contaminated with viruses or other microbes. But that is not all: in future work, the freed-up genetic code could be repurposed to make cells churn out designer enzymes, proteins and drugs.

In 2010, US scientists announced the creation of the world’s first organism with a synthetic genome. The bug, Mycoplasma mycoides, has a smaller genome than E coli – about 1m base pairs – and was not radically redesigned. Commenting on the latest work, Clyde Hutchison, from the US research group, said: “This scale of genome replacement is larger than any complete genome replacement reported so far.”

“They have taken the field of synthetic genomics to a new level, not only successfully building the largest ever synthetic genome to date, but also making the most coding changes to a genome so far,” said Tom Ellis, a synthetic biology researcher at Imperial College London.

But the records may not stand for long. Ellis and others are building a synthetic genome for baker’s yeast, while Harvard scientists are making bacterial genomes with more coding changes. That the redesigned E coli does not grow as well as natural strains is not surprising, Ellis added. “If anything it’s surprising it grows at all after so many changes,” he said.

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U.S. scientists try 1st gene editing in the body

The Associated Press
CBC.ca

Scientists for the first time have tried editing a gene inside the body in a bold attempt to permanently change a person’s DNA to try to cure a disease.

The experiment was done Monday in California on 44-year-old Brian Madeux. Through intravenous (IV), he received billions of copies of a corrective gene and a genetic tool to cut his DNA in a precise spot.

“It’s kind of humbling” to be the first to test this, said Madeux, who has Hunter syndrome, a metabolic disease. “I’m willing to take that risk. Hopefully it will help me and other people.”

Signs of whether it’s working may come in a month; tests will show for sure in three months.

If it’s successful, it could give a major boost to the fledgling field of gene therapy. Scientists have edited human genes before, altering cells in the lab that are then returned to patients. There also are gene therapies that don’t involve editing DNA.

But these methods can only be used for a few types of diseases. Some give results that may not last. Some others supply a new gene like a spare part, but can’t control where it inserts in the DNA, possibly causing a new problem like cancer.

This time, the gene tinkering is happening in a precise way inside the body. It’s like sending a mini-surgeon along to place the new gene in exactly the right location.

“We cut your DNA, open it up, insert a gene, stitch it back up. Invisible mending,” said Dr. Sandy Macrae, president of Sangamo Therapeutics, the California company testing this for two metabolic diseases and hemophilia. “It becomes part of your DNA and is there for the rest of your life.” Continue Reading →

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DIY Gene Editing: Fast, Cheap—and Worrisome

BY AMY DOCKSER MARCUS
WALL STREET JOURNAL

Kian Sadeghi has postponed homework assignments, sports practice and all the other demands of being a 17-year-old high-school junior for today. On a Saturday afternoon, he is in a lab learning how to use Crispr-Cas9, a gene-editing technique that has electrified scientists around the world—and sparked a widespread debate about its use. Scientific breakthroughs often raise big ethical questions. Moral concerns around the 1996 cloning of Dolly the sheep or the 2000 announcement of a rough draft of the human genome still reverberate today. The public benefits from scientific advances, particularly in improving health. Continue Reading →

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Gene-edited ‘micropigs’ to be sold as pets at Chinese institute

BY DAVID CYRANOSKI
NATURE

Cutting-edge gene-editing techniques have produced an unexpected byproduct — tiny pigs that a leading Chinese genomics institute will soon sell as pets.

BGI in Shenzhen, the genomics institute that is famous for a series of high-profile breakthroughs in genomic sequencing, originally created the micropigs as models for human disease, by applying a gene-editing technique to a small breed of pig known as Bama. On 23 September, at the Shenzhen International Biotech Leaders Summit in China, BGI revealed that it would start selling the pigs as pets. The animals weigh about 15 kilograms when mature, or about the same as a medium-sized dog.

At the summit, the institute quoted a price tag of 10,000 yuan (US$1,600) for the micropigs, but that was just to “help us better evaluate the market”, says Yong Li, technical director of BGI’s animal-science platform. In future, customers will be offered pigs with different coat colours and patterns, which BGI says it can also set through gene editing.

With gene editing taking biology by storm, the field’s pioneers say that the application to pets was no big surprise. Some also caution against it. “It’s questionable whether we should impact the life, health and well-being of other animal species on this planet light-heartedly,” says geneticist Jens Boch at the Martin Luther University of Halle-Wittenberg in Germany. Boch helped to develop the gene-editing technique used to create the pigs, which uses enzymes known as TALENs (transcription activator-like effector nucleases) to disable certain genes.

How to regulate the various applications of gene-editing is an open question that scientists are already discussing with agencies across the world. BGI agrees on the need to regulate gene editing in pets as well as in the medical research applications that make up the core of its micropig activities. Any profits from the sale of pets will be invested in this research. “We plan to take orders from customers now and see what the scale of the demand is,” says Li. Continue Reading →

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Henrietta Lacks: Family win recognition for immortal cells

BBC News

Henrietta Lacks, a poor black woman from Maryland, had cells removed from her by doctors when she was being treated for terminal cancer in 1951. Researchers found they were the first human cells that could be grown indefinitely in a laboratory. The historic breakthrough paved the way for countless medical treatments. The story of how an African-American tobacco farmer unwittingly transformed biomedicine was made famous by a 2010 best-seller, The Immortal Life of Henrietta Lacks. ‘Left in the dark’

She was 31 years old when she died of cervical cancer at Baltimore’s Johns Hopkins Hospital. Continue Reading →

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