CRISPR cups turn gels into biological watchdogs

Is there anything that CRISPR can not do? Scientists have used the gene editing tool to create dozens of genetically modified organisms, as well as to track the development of animals, detect diseases and fight pests. Now they have found another application: use CRISPR to create smart materials that change shape on demand.

Researchers have reported that changing-shape materials could be used to deliver drugs and create sentinels for almost all biological signals. Science August 22¹. The study was led by James Collins, a bioengineering engineer at the Massachusetts Institute of Technology in Cambridge.

The Collins team worked with polymers filled with water that are held together by DNA strands, called DNA hydrogels. To modify the properties of these materials, Collins and his team turned to a form of CRISPR using an enzyme called Cas12a that cuts DNA. (The CRISPR – Cas9 gene editor uses the Cas9 enzyme to cut a DNA sequence at the desired point.) The Cas12a enzyme can be programmed to recognize a DNA sequence specific. The enzyme cuts its strand of target DNA, and then separates single strands of DNA nearby.

This property allowed the researchers to construct a series of CRISPR-controlled hydrogels containing a target DNA sequence and single strands of DNA, which separate after Cas12a recognized the target sequence in a stimulus. Breakage of the single strands of DNA causes the hydrogels to change shape or, in some cases, to dissolve completely, thus freeing up a payload (see "CRISPR-Controlled Gels").

The team has created hydrogels programmed to release enzymes, drugs and even human cells – for example, as part of a therapy – in response to stimuli. Collins hopes that the gels could be used to make smart therapies releasing, for example, anticancer drugs in the presence of a tumor or antibiotics around an infection.

Smart goals

Researchers also integrated CRISPR-controlled hydrogels into electronic circuits. In one approach, they placed hydrogels in a small device called a microfluidic chip, connected to an electronic circuit. The circuit was shut down following detection of genetic material from pathogens, including Ebola and methicillin-resistant bacteria. Staphylococcus aureus (MRSA). The team even used the hydrogels to develop a prototype diagnostic tool that sends a wireless signal when it recognizes genetic material from Ebola in laboratory samples. When a member of the team was wearing a wireless detector in a backpack, he was able to identify positive samples simply bypassing them.

Dan Luo, a biological engineering engineer at Cornell University in Ithaca, NY, says CRISPR hydrogels are an improvement over other reactive hydrogels because scientists can easily determine what triggers a change of material. Past efforts to create smart hydrogels used enzymes that did not cut specific DNA sequences or cut only a small number of specific sequences, limiting their adaptability.

"We are in the CRISPR age," says Collins. "It's biology and biotechnology. We have shown that it can make a breakthrough in materials and biomaterials. "