Scientists from Broad Institute of MIT and Harvard in Cambridge,
Massachusetts used CTISPR-Cas9 to transform DNA into a sensitive recording
device that can document the duration and order of events occurring within
cells - and even delete and re-record data in the same genome. The research
findings are published in Science.
According to David Liu, a chemical biologist from Broad Institute, the
inspiration for the cellular recorders was the flight data recorder in
planes. Together with chemist Weixin Tang, Liu harnessed the DNA-slicing
power of Cas9 to engineer a cellular recorder using plasmids. They altered
three DNA letters in one plasmid, so that it carries a sequence targeted by
a guide RNA. The researchers also engineered the bacterium to express Cas9
only when a particular antibiotic is present.
Bacteria do not have the DNA-repair abilities of mammalian cells to fix the
damage caused by Cas9, instead, when the plasmid is targeted by Cas9, it is
degraded. Then, another plasmid replicates to take the place of the degraded
one. The researchers placed the altered and normal plasmids into the cells
and measured the relative ratio of the two. The proportion of altered
plasmid fell in cells that had been treated with antibiotic, because the
cells had begun to degrade the altered plasmids.
This led to an unusually sensitive recorder that allowed the researchers to
read out information from as few as ten bacterial cells. The magnitude of
change revealed the amount of antibiotic present, as well as the duration of
exposure. They also developed techniques for resetting the ratio of altered
to unaltered plasmid, erasing the first recording and preparing the cell to
document the next event using the same set of plasmids.