The ability to selectively switch enzymes on and off in a particular tissue could offer many improved treatment options, and scientists at the University of Florida have now devised a way of achieving this goal. Writing in the journal PNAS, they describe a molecule consisting of a DNA aptamer attached by a polyethylene glycol linker to a complementary strand of DNA with azobenzene molecules attached. The aptamer was chosen to bind selectively to the enzyme thrombin and block its role in blood coagulation. In visible light, the azobenzene double bonds are in the trans-conformation and the aptamer is prevented from binding to thrombin by hybridisation with the complementary strand of DNA. When irradiated with ultraviolet light, however, the azobenzene molecules flip into the cis-conformation causing dissociation of the duplex and unveiling the aptamer which can then bind to thrombin and inhibit blood clotting.
The team hope that the technique could one day be used to cut off the blood supply to solid tumours or to produce controlled release versions of drugs which would be activated only in the target tissue, thus reducing the risk of side effects. Endoscopic lights could be used to activate the drugs or, in some cases, it may be sufficient to irradiate skin close to the target site with near-infrared light which penetrates the skin.