A new biocompatible strategy for photoinduced DNA interstrand cross-linking is presented. Methylene blue induced O-1(2) formation triggers furan oxidation; the resulting aldehyde then rapidly reacts with complementary A or C with formation of stable adducts. Easily accessible furan modified nucleosides, a commercially available photosensitizer, and visible light irradiation constitute the necessary tools to achieve selective duplex interstrand cross-linking.