Compact CRISPR systems found in some of world’s smallest microbes

UC Berkeley scientists have discovered simple CRISPR systems similar to CRISPR-Cas9 — a gene-editing tool that has revolutionized biology — in previously unexplored bacteria that have eluded efforts to grow them in the laboratory. 

The new systems are highly compact, befitting their presence in some of the smallest life forms on the planet. If these systems can be re-engineered like CRISPR-Cas9, their small size could make them easier to insert into cells to edit DNA, expanding the gene-editing toolbox available to researchers and physicians.

In CRISPR-Cas systems, the Cas protein is the scissors. When targeted to a specific sequence of DNA, the Cas protein binds and severs double-stranded DNA. The new discovery nearly doubles the number of simple and compact CRISPR-Cas systems potentially useful as laboratory and biomedical tools.

To date, only three compact Cas proteins — called Class II systems — have been experimentally shown to cut DNA: Cas9, Cpf1 and C2c1. A fourth, C2c2, cuts RNA. “These simple systems are as rare as hen’s teeth. We searched a massive amount of data that included 155 million proteins and only found two: CasX and CasY.” The team also found the first CRISPR-Cas9 system in some of the world’s smallest microbes: a nano-scale member of the archaea, which is a sister group to the bacteria.

Some 40 percent of cultivable bacteria and most archaea are thought to use CRISPR-acquired immunity, but the majority of CRISPR-Cas systems use a complex array of Cas proteins to cut viral DNA.