CRISPR-Cas9 proves an effective tool for recording information on events at the cellular level
CRISPR-Cas 9, the miracle gene-editing tool, has been turned into a recording device that can record the timeline of events within cells. It can also be used to re-record information in the same genome. The latest research, that joins a clutch of others on CRISPR-based recording, will help track changes in expression of genes, a cell’s parentage and even indicate changes in the environment in which the cell has been. CRISPR-based recorders can record stimuli delivered to the cell and cell-signalling changes. Scientists at the Broad Institute used CRISPR-Cas9’s to slice DNA and generate a cellular recorder using circular bacterial DNA called plasmids. The scientists, as per a report in Nature—the study itself has been published in Science—altered three DNA letters (purines and pyrimidines, or nitrogenous bases that are the fundamental units of DNA) in a plasmid to correspond with a sequence targeted by a guide RNA that is part of the CRISPR-Cas9 gene editing.
The bacteria itself was modified to express Cas9 in the presence of a particular antibiotic. With rudimentary DNA-repair functions, bacterial plasmid degraded when targeted by Cas9. Another newly generated plasmid then takes its place. By tracking the number of altered and normal plasmids in a cell over time—the number of plasmids fell in the cells treated with the particular antibiotic—the scientists hit upon a very accurate recorder. The scale of change in proportion was an indicator of the amount of antibiotic used and the time for which the cell was exposed to the antibiotic.
The researchers next focussed on developing ways to reset the proportion of normal and altered plasmids to see if cellular information could be re-recorded. They have since replicated the recorder in mammalian cells’ genomes. This is expected to provide information on how different cells assume different physiology and functions. That, in turn, could be of great help in understanding point defects in genes and even larger replication errors, opening doors for responding to these medically.