Short nucleic acid fragments can form stable paired structures in water when captured inside a protective cage molecule, reports a study online in Nature Chemistry this week. This research reinforces the importance of the hydrophobic effect in base-pairing, and may have implications for molecular information processing. Although such short nucleotides do not normally pair-up to form hydrogen-bonded duplexes in water, they are known to do so in the hydrophobic pockets of enzymes. Mimicking this concept, Makoto Fujita and colleagues made molecular cages from rigid organic molecules held together with metal ions. These structures can be dissolved in water, and have a hydrophobic cavity inside which short mono- and dinucleotides pair up to form stable duplexes. The cages are modular in design and can be easily expanded to accommodate larger nucleic acids by choosing different building blocks. Just as in nature, where short nucleotide fragments can pair up to pass along genetic information, the formation of duplexes inside artificial molecular cages could lead to new systems capable of processing molecular information. In an accompanying News & Views article, Jim Thomas suggests that this study may provide some clues to the further development of DNA-based computing systems.