The first patient dosed with an in vivo gene editing therapy was treated at UCSF Benioff Children's Hospital Oakland as part of Sangamo Therapeutics' clinical trial. The phase 1/2 CHAMPIONS study launched in November is an open-label trial that will evaluate single ascending IV doses of Sangamo's SB-913, a zinc finger nuclease (ZFN)-mediated gene editing therapy for treating mucopolisaccharidosis II (MPS II) or Hunter's syndrome. MPS II is a progressive inherited lysosomal storage disorder caused by mutations in the gene encoding iduronate-2-sulfatase enzyme, which degrades glycosaminoglycans. Depending on the severity of the mutation and the degree of residual enzyme activity, children with this may experience delays in cognitive development, enlarged organs, cardiovascular disorders, hearing loss, stunted growth and skeletal abnormalities, owing to a buildup of toxic carbohydrates in cells throughout their body. One in 100,000–170,000 people are estimated to be born with MPS II. The current standard of care is enzyme replacement therapy that requires regular infusions. The open-label trial will test for safety, vector clearance and the change from baseline in urinary glycosaminoglycans. Sangamo aims to use genome editing to insert a corrective gene into the precise location within the albumin gene using adeno-associated virus vectors that specifically target the liver. The ability to introduce the therapeutic gene permanently could enable a patient's liver to produce a stable supply of the missing enzyme. Sangamo's in vivo genome editing approach allows the therapeutic gene to integrate precisely into the genome, whereas conventional AAV cDNA gene therapy and lenti- or retroviral-based approaches insert randomly. SB-913 has Fast Track, Orphan Drug and rare pediatric disease designations in the US to treat MPS II. Two additional clinical trials are underway in the US to evaluate Sangamo's in vivo genome editing therapeutics for hemophilia B and MPS I, also known as Hurler or Hurler-Scheie syndrome.
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First in vivo human genome editing trial. Nat Biotechnol 36, 5 (2018). https://doi.org/10.1038/nbt0118-5b
Nature Biotechnology (2021)