A research team at Stanford University School of Medicine has developed a new miniature gene-editing system designed to edit the genome of living organisms, CEP magazine wrote.

The system, derived from the defences of single-celled organisms called archaea, is similar to the CRISPR-Cas9 gene-editing tool, according to the October report.

CRISPR-Cas9 is derived from bacteria and is made up of two parts: a guide RNA that can bind to DNA, and Cas9, an enzyme that can slice the DNA at the spot the guide RNA targets, according to the CEP report.

Bacteria and archaea used these systems to destroy invading viruses, but with the right bioengineering techniques, these tools could be used to turn genes on and off in humans and also alter genes by changing their sequences, the report said.

The ultimate goal was to cure genetic diseases by snipping out dysfunctional genes and replacing them with sequences that worked properly, CEP wrote.

That idea was already being tested in humans with clinical trials using CRISPR-Cas9 to cure a condition called Leber’s congenital amaurosis 10 (LCA10), which causes blindness, starting last March, according to the report.

However, CRISPR-Cas9 had its limits, the report said, as the Cas9 enzyme was large, with up to 1,500 amino acids. That made it too large to deliver into living organisms with proven delivery vessels such as lipid nanoparticles or adeno-associated viruses, Stanford University School of Medicine bioengineer Stanley Qi said.

Bacteria and archaea had a suite of CRISPR-Cas systems beyond Cas9, Qi said. However, with more than 99% of those discovered to date inactive in mammalian cells, Qi said his team wanted to investigate if that could be changed.

The team selected an enzyme, Cas12f, which was only 400-700 long, and set about tweaking the enzyme and its guide RNA to better interact with human DNA, the report said.

Following tests showing that Cas12f was not active in mammalian cells, the team used computational tools to simulate the enzyme’s three-dimensional folding structure, using other enzymes in the same family for reference, CEP wrote.

This helped the team determine promising mutation targets that would likely improve the system’s ability to bind with human DNA, according to the report.

The researchers then tweaked Cas12f through mutation, the report said, and tested the system in vitro in cells derived from human kidneys, focusing on switching on a panel of diverse genes, including ones associated with sickle-cell anaemia, HIV infection and the immune system.

“It was a great moment for us to see that even after the first round of mutation, we start to see some enhancement [in the enzyme’s activity],” Qi was quoted as saying.

Over time, the new system — dubbed CasMINI by the researchers for its small size — became effective at activating these genes, the report said.

The researchers did not compare it directly with Cas9, according to the report, with Cas9 and Cas12f having different binding targets on DNA.

However, they found CasMINI to be comparable to the larger Cas12a enzyme, which was known to be almost as effective as Cas9, the report said.

“For some sites, the CasMINI is better, for some sites the Cas12a is better, so overall the two enzymes actually showed similar activity,” Qi said.

The researchers found that the system worked not simply to activate and deactivate genes, but to slice and edit them as well, CEP wrote.

Initial results suggested that different versions of the CasMINI system were best-suited for each of these applications, the report said.

The research team is now collaborating with biomedical researchers to test if CasMINI can work in living organisms with delivery methods currently used in clinical applications, according to the report.