Using CRISPR as the "switcher," hydrogels infused with DNA can be programmed to translate biological information into changes in the constituent gel material's properties, researchers say, triggering the gels to release compounds or nanoparticles, for example. The approach presents a new type of highly responsive hydrogel material with tunable functions that can be engineered in response to user-defined DNA targets. The strategy, say the authors, could pave the way for a wide range of in vitro biomedical applications in tissue engineering, bio-electronics and biosensing. Smart materials activated by biological signals have become increasingly important in biomedical applications. Responsive hydrogels built using DNA sequences have been suggested to be particularly well-suited for these purposes. However, current DNA-responsive hydrogels are limited in terms of their programmability, in part due to a lack of sensitivity to DNA actuation triggers. Here, Max English and colleagues present a new type of sensitive and versatile DNA hydrogel system, made by integrating the CRISPR-Cas toolbox. It uses the RNA-guided Cas12a nuclease enzyme to target and cleave DNA complementary to the guide-RNA spacer sequence within the hydrogel, which then triggers the desired material change. To illustrate the wide-ranging applications of their programmable materials, the authors demonstrated the controlled release of compounds, nanoparticles and live cells from within the DNA hydrogel. What's more, English et al. showed that the materials can be designed to act as degradable electrical fuses and fluidic valves capable of wireless radio-frequency identification (RFID) signaling. The simplicity of the "switcher" and an "actuator" setup this approach involves "can facilitate design simplicity for scaling up multiple-layered responsive hydrogels and developing new functions using the same set of building blocks," writes Da Han in a related Perspective.