NIH. US: Genetically modified organisms (GMOs) are widely used in research and
for making pharmaceuticals and other products. However, use of
genetically modified bacteria outside of the lab has been limited by
concerns that they—and the sometimes novel genes they carry—could escape
into the wild.
Scientists have attempted to solve this problem in a variety of
ways, including the creation of bacteria that depend on nutrients they
can’t make themselves. But these bacteria might survive in the wild by
receiving those nutrients from natural organisms.
One potential solution would be to create genetically engineered
bacteria that are dependent on nutrients not found in nature.
Researchers previously changed the genetic code of bacteria to allow
them to incorporate synthetic amino acids (sAAs) into their proteins. A
team led by Dr. Farren Isaacs of the Yale School of Medicine set out
to make such “genomically recoded organisms” (GROs) dependent on sAAs
for survival. Their work was supported by the Defense Advanced Research
Projects Agency, NIH’s National Institute of General Medical Sciences
(NIGMS), and others. The study appeared on February 5, 2015, in Nature.
Each set of 3 nucleotides in a DNA strand, called a codon, directs the
cell to add a specific amino acid to a growing chain to form a protein.
The team modified the genome of Escherichia coli so that the TAG codon directed the bacteria to incorporate sAAs into proteins.
The researchers introduced these TAG codons into 22 essential genes.
They then compared the growth of these bacterial strains in the presence
and absence of sAAs to find those with the lowest “escape
frequencies”—that is, those least able to grow without the sAA. In a
series of experiments, they were able to construct strains with very
low escape frequencies by combining TAGs from the strains with the
lowest escape frequencies.
To eliminate any rescue by natural amino acids, the team chose 4 of
these essential genes dispersed throughout the genome. They then
introduced TAG codons into carefully chosen sites known to be involved
in functional protein–protein interactions. One strain with 3 of the
TAG codons was able to grow well when provided the sAA, but showed no
detectable growth without it.
“This is a significant improvement over existing biocontainment
approaches for genetically modified organisms,” Isaacs says. “This work
establishes important safeguards for organisms in agricultural
settings, and more broadly, for their use in environmental
bioremediation and even in medical therapies.”
Another team led by Dr. George Church of Harvard Medical School published a study in the same issue of Nature
describing a similar result. Such research may lead to new beneficial
proteins and organisms that are designed with multiple safeguards.
— by Brandon Levy and Harrison Wein, Ph.D.