biostudies-literatureHarmatz PNCATS NIH HHSSangamo Therapeutics3587-3600https://www.ebi.ac.uk/biostudies/studies/S-EPMC9734078biostudies-literatureUnknown30(12)Zinc-finger nuclease (ZFN)-based in vivo genome editing is a novel treatment that can potentially provide lifelong protein replacement with single intravenous administration. Three first-in-human open-label ascending single-dose phase 1/2 studies were performed in parallel (starting November 2017) primarily to assess safety and tolerability of ZFN in vivo editing therapy in mucopolysaccharidosis I (MPS I) (n = 3), MPS II (n = 9), and hemophilia B (n = 1). Treatment was well tolerated with no serious treatment-related adverse events. At the 1e13 vg/kg dose, evidence of genome editing was detected through albumin-transgene fusion transcripts in liver for MPS II (n = 2) and MPS I (n = 1) subjects. The MPS I subject also had a transient increase in leukocyte iduronidase activity to the lower nMolecular therapy : the journal of the American Society of Gene TherapyFirst-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B.PMC9734078UL1 TR002489Burton BKCao LRouy DHarmatz PVaidya SMeyer KVillegas AGZeitler JKessler CMShiue LHMuenzer JSwenson WLau HMiller WFalaleeva MPrada CEWong Po Foo CfalseFirst-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B.Zinc-finger nuclease (ZFN)-based in vivo genome editing is a novel treatment that can potentially provide lifelong protein replacement with single intravenous administration. Three first-in-human open-label ascending single-dose phase 1/2 studies were performed in parallel (starting November 2017) primarily to assess safety and tolerability of ZFN in vivo editing therapy in mucopolysaccharidosis I (MPS I) (n = 3), MPS II (n = 9), and hemophilia B (n = 1). Treatment was well tolerated with no serious treatment-related adverse events. At the 1e13 vg/kg dose, evidence of genome editing was detected through albumin-transgene fusion transcripts in liver for MPS II (n = 2) and MPS I (n = 1) subjects. The MPS I subject also had a transient increase in leukocyte iduronidase activity to the lower n2022-01-01T00:00:00Z2022 Dec2026-05-28T01:25:03.536Z2025-06-01T02:33:49.229ZS-EPMC97340783629924010.1016/j.ymthe.2022.10.010