adenine base editor with guide RNA for MMAB R186W

An investigational, variant-specific **in vivo adenine base-editing therapy** for methylmalonic acidemia caused by the pathogenic **MMAB c.556C>T (p.Arg186Trp; R186W)** variant. The reported approach delivers adenine base editor mRNA together with an optimized hybrid guide RNA in lipid nanoparticles to hepatocytes, aiming to convert the disease-associated allele back to wild type without generating a DNA double-strand break. In cellular studies, the lead editor and guide RNA pair produced efficient corrective editing with low bystander and off-target editing; early liver editing was also reported in a humanized mouse model. The program is an academic preclinical research approach and has no reported product name, sponsor code, commercial developer, clinical trial, or marketed formulation. ([biorxiv.org](https://www.biorxiv.org/content/10.64898/2026.03.12.711365v1))