The specificity of molecular recognition between complementary nucleotide sequences (base pairs) in DNA provides an exciting tool for the development of DNA-based materials with controlled architecture and designed functionality. Scientists have already fabricated a zoo of DNA structures, from nanoparticles and planar structures to extended three-dimensional networks such as gels. However, while DNA hydrogels offer potentially useful properties, their formation and breakdown can be slow, on the order of days, limiting practical opportunities in controlled release applications such as drug delivery.

Fig. 1: Schematic diagram showing a network of interlocking Y-shaped DNA assemblies.

Now, Cheng and colleagues from China and the UK1 report the design of an extended DNA hydrogel using interlocking strands of DNA that can assemble and disassemble within a minute. These single strands hybridize to each other to form a ‘Y’ shape, with a portion of every single strand emanating from each terminal of the Y. At high pH, the extending units form random coils and are similarly charged, causing the extensions to repel each other and thus preventing gelation. But at low pH, these cytosine-rich domains become protonated and form hydrogen bonds with unprotonated cytosines at the opposite end of a DNA strand extending from another Y structure. The researchers designed the Ys so that the three extending domains bend in different directions, ensuring that each unit bonds with another Y to form a network (Fig. 1).

The DNA gelled within one minute when hydrochloric acid was added to the DNA solution, whereas the addition of sodium hydroxide resulted in disassembly. The researchers trapped gold nanoparticles in their gel and observed stable encapsulation for days, and rapid release on exposure of the system to the alkali. Further tests examined the rheology of the system and confirmed the formation and disassembly of a material with gel-like properties with varying pH.

Cheng's team also found that the strength of the gel was temperature-dependent. The Y assemblies have a melting point of around 37 °C, above which the researchers found that their hydrogel fell apart. The material could be designed with specific melting points by modifying the DNA sequences, meaning the product could be useful in drug delivery applications exploiting the local temperature variations of tumor tissue, say the researchers.