Metagenomi Reports Study Showing CRISPR Editing Efficiency; Findings Support Development of Deliverable Gene Editing Systems

Metagenomi Therapeutics, Inc. (NASDAQ:MGX) (the "Company"), an in vivo genome editing company capitalizing on its proprietary technologies to create curative genetic medicines for patients, today announced a publication in Nature Structural & Molecular Biology highlighting the discovery and detailed characterization of MG119-28, a compact CRISPR nuclease with superior editing efficiency relative to previously identified compact nucleases.

The publication, titled "Comparative characterization of Cas12f orthologs reveals mechanistic features underlying enhanced genome editing efficiency" highlights the potential of MG119-28 (formally named Al3Cas12f) to overcome low editing efficiency in mammalian systems of previously identified compact nucleases from the Cas12f class.

The publication demonstrates that the enhanced editing performance is due to superior structural stability of the protein and inherently more stable guide RNA which enables faster DNA cleavage activity. The structural and mechanistic insights enabled engineering of MG119-28 to further improve activity across multiple target genes.

"The ability to pair compact size with high editing efficiency has been a longstanding challenge in the field," said Jian Irish, Ph.D., M.B.A., President and Chief Executive Officer of the Company. "These findings support a path toward building clinically relevant genome editing systems that are both deliverable to tissues outside of the liver via AAV and capable of achieving the levels of activity needed for therapeutic impact. We believe that MG119-28 represents an important step forward for future applications of our platform and the broader field of in vivo gene editing."

This most recent study was conducted in collaboration with researchers from the University of Texas at Austin. It builds on the elegant in vivo proof of concept for MG119-28 presented at the ASGCT meeting in 2025 in which the Company demonstrated 64% knockdown of Atxn2 protein in mice after direct injection of a single AAV delivering MG119-28 and a targeting guide. The Company views this data as encouraging as it explores opportunities to advance its gene editing beyond hepatic indications to treat unmet medical needs in neuromuscular disease targets.f