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Making smart materials with CRISPR

The genome-editing tool helps create gels that react to DNA.
October 24, 2019
A gel created at MIT can be degraded by DNA-editing enzymes. Top: gel (1a) exposed to DNA that doesn’t contain the trigger sequence remains intact (1b). Bottom: gel (2a) breaks down (2b) after two hours of exposure to a DNA “trigger sequence.”
A gel created at MIT can be degraded by DNA-editing enzymes. Top: gel (1a) exposed to DNA that doesn’t contain the trigger sequence remains intact (1b). Bottom: gel (2a) breaks down (2b) after two hours of exposure to a DNA “trigger sequence.”Courtesy of the researchers

The CRISPR genome-editing system is best known for its potential to correct disease--causing mutations and add new genes to living cells. Now, a team from MIT and Harvard University has deployed CRISPR for a completely different purpose: creating novel materials, such as gels, that can change their properties when they encounter specific DNA sequences.

The researchers showed they could use CRISPR to control electronic circuits and microfluidic devices, and to release small molecules, proteins, or living cells from gels. Such materials could be used to create diagnostic devices for diseases such as Ebola or cancer, or to deliver treatments for diseases such as Crohn’s and ulcerative colitis.

“This study serves as a nice starting point for showing how CRISPR can be utilized in materials science for a really wide range of applications,” says James Collins, a professor of medical engineering and science and senior author of the study, which appeared in Science.

CRISPR is based on DNA-cutting proteins called Cas enzymes, which bind to short RNA guides that direct them to specific areas of the genome. Cas cuts DNA in those locations, deleting a gene or allowing new genetic sequences to be introduced. Collins and his colleagues set out to adapt it to create materials that incorporate single--stranded DNA in key functional or structural roles, allowing the new materials to respond to external cues such as the presence of a certain sequence of DNA.

In one demonstration, the researchers designed a gel made of polyethylene glycol (PEG) and used DNA to anchor enzymes or other large biomolecules to the gel. When activated by a trigger sequence, CRISPR enzymes cut the DNA anchors, releasing the payload. The researchers also created an acrylamide gel in which single-stranded DNA forms an integral part of the gel structure. In that case, when CRISPR is activated by the trigger, the entire gel breaks down, enabling the release of larger cargoes such as cells or nanoparticles.

This approach could also lead to CRISPR-controlled diagnostic devices that incorporate a DNA-containing gel, which acts as a valve. If a blood sample flowing through a microfluidic device contained a target DNA sequence, such as that of Ebola, the gel would not form, leaving the valve open and indicating a positive result. The microfluidic sensor can be connected to an RFID chip, allowing it to wirelessly transmit the results of the test.

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