Recent advances in gene-editing technologies and regulatory approaches are enabling the development of therapies for ultrarare diseases affecting fewer than one in 50,000 people. A landmark case involved a custom CRISPR therapy administered to a nine-month-old infant with CPS1 deficiency. Collaborations among biotech firms developed delivery platforms such as lipid nanoparticles and base editors. Despite complexities in genetic variation limiting broad product use, platform technologies allowing modular approvals bring promise for personalized treatments in ultrarare genetic disorders.