Optical UV-A biosensor platform for high-throughput testing of UV-blockers

ABSTRACT Ultraviolet (UV) radiation is a major public health concern, linked to skin cancer, eye damage, immune suppression, and premature aging. Yet despite decades of innovation, the gold standard for sunscreen evaluation, SPF and UVA-PF testing in human volunteers, remains empirical, ethically questionable, and highly variable. Here, we present an Assay for UV-A Radiation Assessment (AURA), a high-throughput, cell-based biosensor that luminesces in response to UV-A exposure (320–400 nm). AURA-transgenic human cells express a membrane-anchored, photocleavable PhoCl domain fused to the tetracycline repressor (TetR) and viral activator VP16, with nuclear export signals ensuring minimal basal activity. Upon UV-A illumination, PhoCl cleavage liberates TetR–VP16, which translocates to the nucleus and activates a tetracycline-responsive reporter. This molecular design enables sensitive detection of 365 nm and 395 nm light with up to 100-fold induction. By combining precision, reproducibility, and ethical advantages, AURA establishes a powerful platform for the high-throughput testing of UV-blockers and offers a transformative alternative to in vivo UVA-PF assessment.