Bioengineers have repurposed a “non-working” CRISPR system to make a smaller version of the genome engineering tool. Its diminutive size should make it easier to deliver into human cells, tissues and the body for gene therapy.• 3 September 2021

BY TAYLOR KUBOTA

The common analogy for CRISPR gene editing is that it works like molecular scissors, cutting out select sections of DNA. Stanley Qi, assistant professor of bioengineering at Stanford University, likes that analogy, but he thinks it’s time to reimagine CRISPR as a Swiss Army knife.

“CRISPR can be as simple as a cutter, or more advanced as a regulator, an editor, a labeler or imager. Many applications are emerging from this exciting field,” said Qi, who is also an assistant professor of chemical and systems biology in the Stanford School of Medicine and a Stanford ChEM-H institute scholar.

The many different CRISPR systems in use or being clinically tested for gene therapy of diseases in the eye, liver and brain, however, remain limited in their scope because they all suffer from the same flaw: they’re too large and, therefore, too hard to deliver into cells, tissues or living organisms.

In a paper published Sept. 3 in Molecular Cell, Qi and his collaborators announce what they believe is a major step forward for CRISPR: An efficient, multi-purpose, mini CRISPR system. Whereas the commonly used CRISPR systems – with names like Cas9 and Cas12a denoting various versions of CRISPR-associated (Cas) proteins – are made of about 1000 to 1500 amino acids, their “CasMINI” has 529.

The researchers confirmed in experiments that CasMINI could delete, activate and edit genetic code just like its beefier counterparts. Its smaller size means it should be easier to deliver into human cells and the human body, making it a potential tool for treating diverse ailments, including eye disease, organ degeneration and genetic diseases generally.