Upon activation by specific natural or user-defined DNA stimuli, a CRISPR-Cas enzyme enables a variety of smart materials to release bound cargo such as fluorescent dyes and active enzymes, change their structures to deploy encapsulated nanoparticles and live cells, or regulate electric circuits thereby converting biological into electric signals.
"Our study shows that the power of CRISPR can be harnessed outside of the laboratory for controlling the behavior of DNA-responsive materials. We developed a range of materials with very different capabilities that highlight the breadth of applications enabled by programmable CRISPR-responsive smart materials," said Wyss Institute Founding Core Faculty member James Collins, Ph.D., who led the study and is a leader of the Institute's Living Cellular Devices platform. "These applications include novel theranostic strategies, point-of-care diagnostics, and the regional monitoring of epidemic outbreaks and environmental hazards." Collins also is the Termeer Professor of Medical Engineering & Science and a Professor of Biological Engineering at MIT.
The CRISPR-Cas system has gained its fame because of its ability to find almost any target sequence in the genome with the help of a short complementary guide-RNA (gRNA), and to cut and repair the DNA double strand with surgical precision. In the present study, the team leveraged a Cas enzyme variant known as Cas12a from a Lachnospiraceae bacterium that has the same ability to recognize and cut specific DNA sequences but, activated by this event, importantly, carries on to non-specifically cleave single-stranded DNA in its vicinity at a rate of about 1250 turnovers per second.
"We incorporated single-stranded target DNA sequences into polymeric materials, either as anchors for pendant cargos, or as structural elements that maintain the materials' basic integrity, and can control different material behaviors just by providing Cas12a together with a specific gRNA as a stimulus," said co-first author Max English, who is an MIT graduate student working with Collins.
MEDICA-tradefair.com; Source: Wyss Institute for Biologically Inspired Engineering at Harvard