Responsive MXene nanovehicles deliver CRISPR/Cas12a for boolean logic-controlled gene editing

Programmable and precise regulation of genetic information is crucial in bioengineering and biomedicine; however, it remains challenging to implement this objective. Here we deployed DNA-functionalized MXenes as a smart delivery system for spatiotemporally controllable genome editing. The MXene nanovehicles rationally integrated photothermal effect with nucleic acid strand displacement reaction, thereby allowing for the binary logic gate-controlled release of Cas ribonucleoprotein complexes in response to different input patterns of NIR light and nucleic acids. This system was highly programmable and could be harnessed to construct 2-input (AND, OR, and N-IMPLY) and 3-input (AND/OR and N-IMPLY/OR) logic gates for precise gene editing in mammalian cells. Moreover, an AND logic gate-controlled delivery system achieved selective induction of tumor cell death in a xenograft mice model using tissue-penetrating NIR light and cancer-relevant microRNA as the inputting cues. Therefore, the MXene nanovehicles adopted both the external and endogenous signals as the stimuli to precisely control gene editing under logic computation, presenting a helpful strategy for therapeutic genome editing.