PM359

**PM359** is an autologous ex vivo hematopoietic stem cell therapy developed by Prime Medicine using prime editing technology to correct the delGT mutation (2-base pair GT deletion) in the *NCF1* gene, the most common cause of p47phox-deficient chronic granulomatous disease (CGD), affecting approximately 25% of CGD cases. It involves harvesting patient CD34+ HSCs, electroporating them with prime editing machinery to restore the sequence to GTGT (including in pseudogenes), and reinfusing after myeloablative conditioning with busulfan. In first-in-human Phase 1/2 data, a single IV dose achieved rapid engraftment, restored NADPH oxidase activity to 58-66% of neutrophils by Day 30 (exceeding the 20% clinical benefit threshold), with 68-91% corrected alleles in products and no serious PM359-related AEs; two adult patients remained free of new CGD complications short-term. PM359 has FDA Orphan Drug and Rare Pediatric Disease designations, with IND cleared in May 2024, but Prime Medicine announced it will not advance independently and is seeking external partners.[1][2][3][9]