ROSAH syndrome is a rare genetic disease caused by a mutation in the human alpha kinase 1 (ALPK1) gene (p.Thr237Met), leading to vision loss, swollen optic nerves, dry mouth, enlarged spleen, and frequent headaches. Researchers in the Laboratory of Clinical Immunology and Microbiology (LCIM) at the National Institute of Allergy and Infectious Diseases (NIAID) have developed a new approach that can precisely fix the ALPK1 mutation without causing unwanted changes in the patient’s DNA. This method uses a base editor combined with a guide RNA to safely and efficiently convert the pathogenic thymine of the mutation back to cytosine. In laboratory tests, this gene editing technology successfully repaired the mutation in patient-derived affected cells with high accuracy and no side effects.
This therapy could be delivered directly to the eye or salivary glands, or patient cells could be corrected outside the body and then returned to the patient, offering hope for personalized treatment to restore vision and improve quality of life for people with ROSAH syndrome.