Metagenomi, a precision genetic medicines company committed to developing curative therapeutics for patients using its proprietary gene editing toolbox, today announced a publication in the journal Nature Communications describing its novel, compact CAST system for large, targeted gene integration into the human genome.
Metagenomi’s CAST systems are a potential solution for development of curative genetic medicines, as these natural systems perform a task critical to the field of gene editing: precise, programmable integration of large gene cargoes.
This technology has the potential to address a large collection of complex genetic diseases caused by any loss of function mutations, such as Wilson’s disease, cystic fibrosis, and Duchenne Muscular Dystrophy. The newly published data demonstrates a first-in-class approach to precisely integrating therapeutic genes into the human genome, building on prior findings that established the potential of these systems.
Metagenomi’s novel, compact Cas12k CAST system was discovered using the company’s AI-driven metagenomics platform and translated to achieve programmable and targeted genomic integration in human cells. Metagenomi scientists demonstrated integration of multiple cargoes to a known safe-harbor site in the human genome, illustrating the site-specific, programmable, and versatile attributes of the system.
The study highlights key advancements for the translation of CAST for therapeutic applications, including the ability to re-target to a safe-harbor site in the human genome, complete integration of a therapeutically-relevant gene, and streamline delivery using an ‘all-in-one’ mRNA. These findings provide new insights into large, targeted genomic integration approaches for the development of in vivo gene editing therapeutics. Future work will focus on expanding these capabilities and optimizing the system for clinical applications, with additional advancements expected in 2025.
