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Programmable CRISPR-responsive smart materials

Max A. English,L. Soenksen,Raphael V. Gayet,Helena de Puig,Nicolaas M. Angenent-Mari,Angelo S. Mao,P. Nguyen,J. Collins

Published 2019 in Science

ABSTRACT

A CRISPR set of materials CRISPR technology is best known as a gene editing tool. English et al. developed a group of stimuli-responsive hydrogels to respond to the programmable nuclease Cas12a (see the Perspective by Han et al.). The materials undergo molecular to macroscopic changes after Cas12a-dependent cleavage of double- or single-stranded DNA integrated into the gel. The authors show controlled release of particles linked to or imprisoned within the DNA, degradation of a gel with DNA solely forming the cross-links, and permeabilization of a gel with DNA partially forming the cross-links. These tools allow for the production of materials that release encapsulated nanoparticles and cells, act as degradable fuses, and enable remote radio-frequency identification signaling. Science, this issue p. 780; see also p. 754 CRISPR-associated nucleases are used to control multiscale properties of DNA-based materials. Stimuli-responsive materials activated by biological signals play an increasingly important role in biotechnology applications. We exploit the programmability of CRISPR-associated nucleases to actuate hydrogels containing DNA as a structural element or as an anchor for pendant groups. After activation by guide RNA–defined inputs, Cas12a cleaves DNA in the gels, thereby converting biological information into changes in material properties. We report four applications: (i) branched poly(ethylene glycol) hydrogels releasing DNA-anchored compounds, (ii) degradable polyacrylamide-DNA hydrogels encapsulating nanoparticles and live cells, (iii) conductive carbon-black–DNA hydrogels acting as degradable electrical fuses, and (iv) a polyacrylamide-DNA hydrogel operating as a fluidic valve with an electrical readout for remote signaling. These materials allow for a range of in vitro applications in tissue engineering, bioelectronics, and diagnostics.

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