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CRISPR-Responsive Gels

CRISPR-Responsive Gels.
DNA is more than just a genetic molecule. Its physical structure and predictable behavior also make it a versatile biological building material. Indeed, DNA has been used to create nanoscale robots, patterns, and 3-D structures for various purposes, and it has been incorporated into hydrophilic polymer gels (hydrogels) for a variety of innovative applications, including biosensing, drug delivery, and more.

But such gels have limited versatility, says Max English, a graduate student in the laboratory of MIT bioengineer Jim Collins. Often, DNA-containing gels are designed with strands that are complementary to the intended DNA activators.
This means that “whenever you want to design a material that responds to a different [DNA] cue, you have to redesign the material in its entirety,” English explains. To avoid such overhauls, English and colleagues created a system for making DNA-containing gels that are capable of responding to nearly any DNA cue simply by providing the CRISPR system’s Cas12a nuclease and a guide RNA (gRNA) that matches the desired DNA trigger. The team exploited a feature of Cas12a called collateral cleavage, in which the enzyme, after cutting its target double-stranded (ds) DNA, nonspecifi cally chops up surrounding singlestranded (ss) DNAs. The hydrogels are thus fabricated with ssDNAs that are cleaved by Cas12a when, and only when, a given gRNA and dsDNA combination is present.

Using this principle, the team created DNA-containing hydrogels that, in response to a dsDNA cue provided by the researchers, could either release DNAbound compounds or fully degrade. Such degradation could be used for applications such as liberating encapsulated contents like cells or nanoparticles, initiating flow of a buff er through a microfl uidic device, or opening an electrical circuit. These last two examples could potentially be used in diagnostic devices, says Collins, with a change in buff er fl ow or electrical output signaling the presence of a DNA sequence of interest in a patient sample.
“They showed some really novel applications of responsive hydrogels,” says Rebecca Schulman, a chemical and biomolecular engineer at Johns Hopkins
University who did not participate in the study, in an email to The Scientist.

“Their approach is totally customizable [and] is really cleverly designed,” adds bioengineer Dan Luo of Cornell University who was not involved in the research. “It’s a real integration of molecular biology and materials science.

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