A modified DNA aptamer that binds BACE1, a therapeutic target involved in Alzheimer's disease has been developed. This ssXNA not only tightly binds to BACE1 but also inhibits its protease activity in vitro in the same range as a previously described unmodified aptamer. We report the in vitro selection of functional oligonucleotides incorporating two nucleobase modifications: 5‐chlorouracil and 7‐deazaadenine. The nucleoside analogue 5‐chloro‐2′‐deoxyuridine has already been explored as a replacement for thymidine in a chemically modified genome of a bacterium. Thus, 5‐chlorouracil modification is a good candidate to support genetic transfer in vivo as well as functional activity
