Scientists have developed CHyMErA, a new CRISPR-based tool for more versatile genome editing applications to help shed light on how multiple genes cooperate in health and disease.

CRISPR-based DNA editing has revolutionized the study of the human genome by allowing precise deletion of any human gene to glean insights into its function. But one feature remained challenging — the ability to simultaneously remove multiple genes or gene fragments in the same cell. Yet this type of genome surgery is key for scientists to understand how different parts of the genome work together in the contexts of both normal physiology and disease.

Now such a tool exists thanks to the teams of Benjamin Blencowe and Jason Moffat, both professors of molecular genetics at the Donnelly Centre for Cellular and Biomolecular Research. Dubbed ‘CHyMErA’, for Cas Hybrid for Multiplexed Editing and Screening Applications, the method can be applied to any type of mammalian cell to systematically target the DNA at multiple positions at the same time, as described in a study published in the journal Nature Biotechnology.

Often described as genome scissors, CRISPR works by sending a DNA-cutting enzyme to desired sites in the genome via guide RNA molecules, engineered to adhere to the target site. The most widely used DNA-cutting enzyme is Cas9.

Since Cas9 first came to light, other Cas enzymes with distinct properties have been identified by scientists seeking to improve and expand the applications of the technology. Unlike the CRISPR-Cas9 technology, CHyMErA combines two different DNA-cutting enzymes, Cas9 and Cas12a, to allow more versatile applications. Cas12a is an enzyme that can be used to generate multiple guide RNA molecules in the same cell, which is key for simultaneous DNA editing.

Thomas Gonatopoulos-Pournatzis, a research associate in Blencowe’s group, had spent several years trying to develop combinatorial gene editing by testing Cas9 and Cas12a enzymes on their own. He then had the idea to combine these enzymes to generate the CHyMErA system.

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Materials provided by University of Toronto. Original written by Jovana Drinjakovic. Note: Content may be edited for style and length.