We’ve seen a number of recent improvements to the CRISPR gene editing method, from enhanced precision to novel techniques to block the process. But despite all these innovations, the technique is generally only able to modify one single gene at a time. An incredible new breakthrough from scientists at ETH Zurich has, for the first time, demonstrated a new CRISPR method that can modify dozens of genes simultaneously, allowing for more large-scale cell reprogramming.

In a recently published paper in the journal Nature Methods, a team of ETH scientists demonstrated their new gene editing process can modify 25 different target sites simultaneously. The scientists say this new technique is not necessarily limited to 25 targets, but theoretically could be increased to hundreds of simultaneous gene modifications.

“Thanks to this new tool, we and other scientists can now achieve what we could only dream of doing in the past,” says Randall Platt, from ETH Zurich in Basel. “Our method enables us, for the first time, to systematically modify entire gene networks in a single step.”

Instead of using the traditional Cas9 enzyme, utilized in most CRISPR work, this technique utilizes the lesser known Cas12a enzyme. Prior research has already revealed the Cas12a enzyme to be slightly more precise in its ability to identify targeted genes, however, the new research reveals Cas12a can also handle shorter RNA address molecules compared to Cas9.

The general CRISPR-Cas technique homes in on its target in a DNA sequence using a pre-designed RNA sequence, called guide RNA. This RNA molecule functions like an address label. The new technique involved the design of a novel plasmid, or circular DNA molecule, that can hold a number of different RNA address labels. One of the strengths of the Cas12a enzyme is its ability to effectively read shorter RNA address sequences.

“The shorter these addressing sequences are, the more of them we can fit onto a plasmid,” explains Platt.

Genes interact with each other in extraordinarily complex ways. So, while single gene editing can be useful when we know a certain condition is caused by just one gene, the reality underlying many disorders is much more complicated. This innovative new technique now allows scientists to explore broad genetic interactions by influencing a number of genes in one single step.

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Dr. Hans C. Mumm