New Gene Editing Tool Allows Editing Without Cutting Double Helix Strands

A study led by Yutaro Shuto, Ryoya Nakagawa, and Osamu Nureki of the University of Tokyo has demonstrated the spatial structure and mechanisms of the gene editing tool called prime editor, revealing its ability to perform reverse transcription without cutting both strands of double helix. Their findings, published in Nature, contribute to the design of precise gene editing tools for gene therapy.

The prime editing system, consisting of a prime editor and a prime editing guide RNA (pegRNA), works as a “word processor” by accurately replacing genomic information. This system has been successfully implemented in various organisms, but the detailed execution of its editing process remains unclear due to insufficient information on its spatial structure.

The research team used cryogenic electron microscopy to observe the prime editor complex at a near-atomic scale and successfully determined its three-dimensional structure. The analysis revealed that the reverse transcriptase maintained its position relative to the Cas9 protein and could result in additional, undesired insertions.

“Our structure determination strategy in this study can also be applied to prime editors composed of a different Cas9 protein and reverse transcriptase. We want to utilize the newly obtained structural information to lead to the development of improved prime editors,” says Shuto, the first author of the paper.

For more information, read the press release from The University of Tokyo School of Science.