Researchers in the laboratory of George Church, Robert Winthrop Professor of Genetics at Harvard Medical School and a core faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard, are working to produce the most modified bacterial genome to date. The researchers believe the method they developed will help others who are trying to make many edits at once to any organism’s genome.
“We are changing the way the DNA code is being translated. Most organisms on Earth use 64 codons to translate their DNA into proteins. Our recoded E. coli is designed to use only 57 codons. We are pushing to unprecedented levels the technologies available for changing whole genomes... We don’t know of any other organism that uses only 57 codons, and it will be very interesting to investigate the effects of large-scale codon exchange.” said Nili Ostrov, a George Church lab postdoctoral researcher who was part of the research team.
The team aimed to make over 60,000 genome modifications in order to replace seven codons at once. This was achieved by designing and synthesising an entirely new E.coli genome, with the modifications built in rather than editing an existing genome.
To determine the success of the project, 55 of the 87 genome segments were analysed to locate problems with the code. To the surprise of the research team, very few faults were found; only 13 of 2229 genes that were tested, far fewer than were anticipated due to the extent of modification.
The purpose of such a project was summed up by Mattieu Landon, a Church lab graduate student:
“The main reason is that the bacterial strain we are trying to build will have new properties useful for medical and industrial applications that are very difficult or impossible to obtain through so-called punctual changes to the genome.
Examples of useful properties are virus resistance and genetic isolation. Many valuable compounds, including drugs such as insulin, are produced using bacterial strains. Usually, if a virus infects a batch of drug-producing bacteria, the whole plant has to be stopped and all the infected batches thrown away. Having virus-resistant bacteria could prevent such problems and potentially save millions of dollars.”