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Cambridge researchers create the world's first living organism with completely redesigned DNA | Science



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

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

The existence of the bug shows that life can exist with a limited genetic code and paves the way for organisms whose biological machines are commandeered to make drugs and useful materials or to add new functions such as virus resistance.

In a two-year effort, researchers at the molecular biology laboratory at Cambridge University, and redefined the DNA of the bacterium read Escherichia coli ([coli) before creating cells with a synthetic version of the altered genome.

The artificial genome contains 4m base pairs, the units in the genetic code spelled out with the letters G, A, T, and C. Printed in its entirety on the A4 sheet, it goes to 970 pages, making the genome the greatest superior to a scientist ever built.

"It was completely unclear whether it was possible to make one through so large and if it was possible to change it so much," says Jason Chin, an expert on synthetic biology who led the project. The DNA coil in a cell holds the instructions it needs to work. For example, when the cell needs more protein to grow, it reads DNA that encodes the right protein. The DNA letters are read in triads called codons, such as TCG and TCA.

Almost all life, from jellyfish to humans, uses 64 codons. But many of them do the same job. In total, 61 codons produce 20 natural amino acids, which can be joined together as beads on a string to build some protein in nature. Three new codons are in fact stop signs: they tell the cell when the protein is made, as the complete stop marks the end of this sentence.





  The new synthetic organism Escherichia coli Syn61 on plates.



The new synthetic organism,
Escherichia coli
Syn61 on plates. Photo: Handout
The Cambridge layer determined to transform the [coli] genome by removing some of its excess codons. [1945] Working on a computer, the researchers went through the bug's DNA. When they came across TCG, a codon that makes an amino acid called serine, they rewrote it as AGC, doing the same job. They replaced two more codons in a similar way.

More than 18,000 edits later, the researchers had removed all occurrences of the three codons from the bug's genome. The redesigned genetic code was then chemically synthesized and added to [coli where it replaced the natural genome of the organism. The result, reported in Nature, is a microbe with a completely synthetic and radically altered DNA code. Known as Syn61, the bug is a bit longer than normal and grows slower, but survives anyway.

"It's pretty amazing," Chin said. When the bug was created just before Christmas, the research group had taken a photo in the lab with a plate of microbes as the central figure in the nativity's recreation.

Such designs could be useful, Chin says. Because their DNA is different, invading viruses will struggle to spread inside them, making them actually virus-resistant. It can bring benefits. 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 diseases, but the whole production can be corrupted when bacterial cultures are contaminated with viruses or other microbes . But that's not all: in the future, the released genetic code can be restored to cause the cells to release designer enzymes, proteins and drugs.


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In 2010, American researchers 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 pair – and was not radically redesigned. Commenting on the latest work, Clyde Hutchison, from the US research team, said: "This extent of throughput is greater than any complete breakthrough reported so far."

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

But the discs may not be long. Ellis and others build a synthetic genome for baker's yeast, while Harvard researchers make bacterial genes with more coding changes. The fact that the redesigned [coli does not grow as well as natural strains is not surprising, Ellis added. "If anything is surprising, it grows at all after so many changes," he said.


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