Researchers advance toward engineering ‘wildly new genome’
In two parallel projects, researchers have rewritten the genetic code of the bacterium E. coli. In the first study they created a genetically and biochemically novel organism by erasing every example of a single codon from the entire genome. In the second, they tested whether all codons could be swapped to a synonymous codon in 42 separate genes, while eliminating every instance of 13 codons throughout each of those genes.
Oct. 17, 2013 — In two parallel projects, researchers have created new genomes inside the bacterium E. coli in ways that test the limits of genetic reprogramming and open new possibilities for increasing flexibility, productivity and safety in biotechnology.In one project, researchers created a novel genome — the first-ever entirely genomically recoded organism — by replacing all 321 instances of a specific “genetic three-letter word,” called a codon, throughout the organism’s entire genome with a word of supposedly identical meaning. The researchers then reintroduced a reprogramed version of the original word (with a new meaning, a new amino acid) into the bacteria, expanding the bacterium’s vocabulary and allowing it to produce proteins that do not normally occur in nature.In the second project, the researchers removed every occurrence of 13 different codons across 42 separate E. coli genes, using a different organism for each gene, and replaced them with other codons of the same function. When they were done, 24 percent of the DNA across the 42 targeted genes had been changed, yet the proteins the genes produced remained identical to those produced by the original genes.”The first project is saying that we can take one codon, completely remove it from the genome, then successfully reassign its function,” said Marc Lajoie, a Harvard Medical School graduate student in the lab of George Church. “For the second project we asked, ‘OK, we’ve changed this one codon, how many others can we change?'”Of the 13 codons chosen for the project, all could be changed.”That leaves open the possibility that we could potentially replace any or all of those 13 codons throughout the entire genome,” Lajoie said.The results of these two projects appear today in Science. The work was led by Church, Robert Winthrop Professor of Genetics at Harvard Medical School and founding core faculty member at the Wyss Institute for Biologically Inspired Engineering. Farren Isaacs, assistant professor of molecular, cellular, and developmental biology at Yale School of Medicine, is co-senior author on the first study.Toward safer, more productive, more versatile biotechRecoded genomes can confer protection against viruses — which limit productivity in the biotech industry — and help prevent the spread of potentially dangerous genetically engineered traits to wild organisms.”In science we talk a lot about the ‘what’ and the ‘how’ of things, but in this case, the ‘why’ is very important,” Church said, explaining how this project is part of an ongoing effort to improve the safety, productivity and flexibility of biotechnology.”These results might also open a whole new chemical toolbox for biotech production,” said Isaacs. “For example, adding durable polymers to a therapeutic molecule could allow it to function longer in the human bloodstream.”But to have such an impact, the researchers said, large swaths of the genome need to be changed all at once.”If we make a few changes that make the microbe a little more resistant to a virus, the virus is going to compensate. …
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