![]() The researchers are now exploring the possibility of using this approach to deliver engineered bacterial cells to help treat gastrointestinal diseases. “The enzyme is able to catalyze the cleavage of the single-stranded DNA, which acts as a structural linker, and release all of those molecules.” “In that context, we consider the single-stranded DNA as a structural scaffold,” Gayet says. In that case, when Cas12a is activated by the trigger, the entire gel breaks down, enabling the release of larger cargoes such as cells or nanoparticles. In another example, they created an acrylamide gel in which single-stranded DNA forms an integral part of the gel structure. That type of gel could be useful for releasing therapeutic compounds such as drugs or growth factors, the researchers say. When activated by a trigger sequence, Cas12a cuts the DNA anchors, releasing the payload. In one example, they created a gel made of polyethylene glycol (PEG) and used DNA to anchor enzymes or other large biomolecules to the gel. The researchers took advantage of this to design gels that incorporate single-stranded DNA in key functional or structural roles. “By incorporating DNA into materials, you can use this enzyme to control the properties of the materials in response to a specific biological cue in the environment,” English says. Once Cas12a encounters a target DNA sequence, also called a trigger, it cleaves the double-stranded DNA and transforms into an enzyme that can slice any single-stranded DNA it encounters. The MIT and Harvard team set out to adapt it for creating materials that could respond to external cues such as the presence of a certain sequence of DNA.įor this work, they used an enzyme known as Cas12a, which can be programmed to bind to specific sequences of double-stranded DNA by simply changing the guide RNA sequence that is given along with the enzyme. Over the past several years, much research has been devoted to developing CRISPR as a gene-editing tool for treating disease by cutting out or repairing faulty genes. Cas cuts DNA in those locations, deleting a gene or allowing new genetic sequences to be introduced. 22 online edition of Science, are MIT graduate students Max Atti English, Luis Soenksen, and Raphael Gayet, and postdoc Helena de Puig.ĬRISPR is based on DNA-cutting proteins called Cas enzymes, which bind to short RNA guides that direct them to specific areas of the genome. The lead authors of the study, which appears in the Aug. “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, the Termeer Professor of Medical Engineering and Science in MIT’s Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering, and the senior author of the study. Such materials could be used to create diagnostic devices for diseases such as Ebola, or to deliver treatments for diseases such as irritable bowel disease. The researchers showed they could use CRISPR to control electronic circuits and microfluidic devices, and to release drugs, proteins, or living cells from gels. 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 CRISPR genome-editing system is best-known for its potential to correct disease-causing mutations and add new genes into living cells.
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