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.
Researchers in the lab of chemical and biomolecular engineer Xue Sherry Gao created a CRISPR-based gene editor designed to target adenine—one of the four main DNA building blocks—that remains inactive when disassembled but kicks into gear once the binding molecule is added.
"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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