Mismatch-Driven CRISPR/Cas12a Biosensing of UV-Induced DNA Lesions for Environmental Solar Exposure Surveillance

Monitoring environmentally relevant ultraviolet (UV) radiation is critical for understanding its biological impacts on ecosystems and human health. However, conventional UV dosimeters lack the molecular sensitivity to detect DNA-level damage that initiates such effects. Here, we present a CRISPR/Cas12a-based biosensing platform capable of quantifying solar UV exposure through the detection of UV-induced thymine dimers in DNA activators. This system harnesses mismatch-driven suppression of Cas12a activity, enabling a reduction in the fluorescence signal in response to UV-induced molecular lesions. The impact of thymine arrangement and the dimerization position of the activators on sensitivity were investigated. UV-induced diminution in Cas12a's trans-cleavage efficiency (k_cat/K_m) was also characterized, revealing a 1.67-fold decrease as the UVB dose increased from 0 to 2 J/cm². Under optimized conditions, the sensor achieved a detection limit of 0.029 J/cm² for UVB and demonstrated high sensitivity to UVC. Field validation under natural sunlight showed a strong correlation with reference radiometric measurements, validating the biosensor's accuracy and environmental relevance. The system's sensitivity to low lesion densities, straightforward mechanism, and simple operation highlights its potential for environmental surveillance, human health risk assessment, and ecological monitoring in response to solar UV radiation.