Split Gene-Editing Tool Offers Greater Precision
Published:10 Dec.2023 Source:Rice University
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. 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.
According to a study published in Nature Communications, the tool developed by Gao and collaborators performed well both in human cell cultures and in living mice, where it accurately edited a single base pair on a target gene. Given that single base-pair mutations ⎯ also known as point mutations ⎯ are responsible for thousands of diseases, the split editor could have broad therapeutic applications. To install an 'on/off' switch, the researchers broke the adenine base editor into two separate proteins that remain inactive until sirolimus (previously known as rapamycin) is added.
Upon introduction of this small molecule, the two separate inactive fragments of the adenine base editor are glued together and rendered active, as the body metabolizes the rapamycin, the two fragments disjoin, deactivating the syste. Compared to an intact editor, the version reduces overall off-target edits by over 70% and increases the accuracy of on-target edits