To make a gene-editing tool more precise and easier to control, engineers split it into two pieces that only come back together when a third molecule is added.
To make a gene-editing tool more precise and easier to control, Rice University engineers split it into two pieces that only come back together when a third small molecule is added.
Compared to the intact original, the split editor is more precise and stays active for a narrower window of time, which is important for avoiding off-target edits. Moreover, the activating small molecule used to bind the two pieces of the tool together is already being used as an anticancer and immunosuppressive drug.
"This tool has the potential to correct nearly half of the disease-causing point mutations in our genome," said Hongzhi Zeng, the lead author of the study and a graduate student in the Gao lab."However, current adenine base editors are in a constant 'on' state, which could lead to unwanted genome changes alongside the desired correction in the host genome.
To install an 'on/off' switch, the researchers broke the adenine base editor into two separate proteins that remain inactive until sirolimus is added ⎯ a molecule discovered in 1972 in soil bacteria on Easter Island that is approved by the U.S. Food and Drug Administration for use in cancer therapies and other medical procedures.
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