Wouldn’t it be great if we could insert a bit of
programmable DNA into an organism’s genome and then modify that DNA after the
fact to contain whatever instructions we wished? Well, we can’t quite do that yet. But we may
be one step closer to that goal, thanks to the work of Jerome Bonnet, Pakpoom
Subsoontorn and Drew Endy of Stanford University. They have designed what they
refer to as ‘rewriteable recombinase addressable data' (RAD) module.
In essence, this is a cartridge of DNA that contains one
set of instructions when inserted in one direction, but at different set of
instructions when inverted. At any point, the researchers can determine which
instructions are given to the cell (in this case E. coli) by controlling the orientation of that cartridge.
The researchers relied on the fact that some types of bacteriophages
(also called phages), have
perfected the art of shuttling their own DNA in and out of their hosts’
genomes. These are viruses that only attack bacteria. They use enzymes
(integrases) to insert their genomes into that of the host cell at strategic
locations. When the viruses are ready to leave the cell, other enzymes (excisionases) clip out the viral DNA and
package it into protein coats.
The RAD module includes the genes for an integrase and an
excisionase. Under some conditions only integrase is made and under others both
are made. When integrase alone is produced, the module is inserted in one
direction. When both are produced, the module is snipped out, inverted and
reinserted in the opposite orientation.
Because the RAD module also encodes fluorescent reporter proteins, the
orientation of the module can be monitored by observing whether the cell glows
red or green.
To be clear, once inserted, the RAD module can’t be
rewritten to include any new instructions. It only contains whatever
nucleotides it started with. In this case, it contained the instructions to
glow red or to glow green. However, the researchers were able to control which
of those two instructions the cell followed. After some fine tuning to prevent
spontaneous flipping, they were able to reliably switch back and forth between
those two sets of instructions.
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