Sangamo Therapeutics has started dosing patients with gene-editing drugs that are administered directly into the blood.

Sangamo's zinc finger nucleases (ZFNs) are enzymes that selectively bind, cleave and enable the directed repair of DNA to knock genes both in and out of patient genomes. In 2011, their first clinical application of a ZFN-based drug relied on ex vivo gene editing; researchers harvested T cells from HIV-positive patients, edited the cells to disrupt the CCR5 gene, and then re-infused these back into the patients in the hopes that the engineered cells would evade infection.

The company's new ZFN products are now designed to edit genes in vivo. In a landmark first in vivo gene-editing trial, patients with the rare lysosomal storage disease mucopolysaccharidosis II (MPS II) received SB-913 intravenously. The drug traffics to the liver, where it inserts a functioning copy of the IDS gene, under the control of the strong albumin promoter, into the genomes of liver cells.

“We are at the start of a new frontier of genomic medicine,” says Sandy Macrae, CEO of Sangamo Therapeutics.

The company is also recruiting patients into trials of two other in vivo ZFNs. SB-318 inserts a copy of the IDUA gene into liver cells, for MPS I. SB-FIX inserts a copy of the gene that encodes factor IX, into liver cells, for haemophilia B.

Other biotechs are gearing up to launch clinical trials of CRISPR-based drugs, which promise more precise and efficient gene-editing activity. CRISPR Therapeutics and Vertex Pharmaceuticals are readying a trial of CTX001, an ex vivo treatment for β-thalassaemia. Editas Medicine is preparing a phase I trial of its lead product, an in vivo treatment for Leber congenital amaurosis. Editas CEO Katrine Bosley recently credited lessons learned with ZFNs as a key to CRISPR's rapid race to the clinic (Nat. Rev. Drug Discov. 16, 672–673; 2017).