Nature Commun. doi:10.1038/ncomms1340 (2011); Nature Commun. doi:10.1038/ncomms1337 (2011)

Nucleic acids have been used as scaffolds to build a variety of programmable structures but the application of these structures inside a living organism has yet to be shown. Previously, Yamuna Krishnan and colleagues at the Tata Institute of Fundamental Research in India showed that a DNA nanomachine (called an I-switch) built from two DNA duplexes can function as a pH sensor inside living cells. Now, in two separate publications the Indian team have shown that the I-switch and a second DNA nanomachine (called the icosahedral) can map pH changes inside a worm.

The I-switch consists of three DNA strands: two strands are partially hybridized to a third strand and the end of one of the two strands consists of an acceptor dye and the other a donor dye pair. At low pH, the assembly adopts a 'closed state' and the pair of dyes gets closer to each other and undergoes fluorescence resonance energy transfer. When injected into the Caenorhabditis elegans worm, the I-switch was taken up by specific cells (known as coelomocytes) into membrane-bound vesicles known as endosomes in a process called endocytosis. The I-switch could map the changes in pH of the maturing endosome inside the living organism.

The DNA icosahedral, also built from DNA motifs, has a central cavity that contained a pH-sensitive fluorescent dye. The encapsulated dye was taken up by cells from the Drosophila fruit fly differently from the free dye and, like the I-switch, the icosahedral–dye complex can map pH changes associated with endosome maturation in coelomocytes of the worm.