The Generative Brain

AAV zinc finger repressor of PRNP (Sangamo with the Broad)

A one-time intravenous AAV zinc finger repressor of PRNP (ST-506) developed by Sangamo with the Broad. Sangamo went through Chapter 11 in 2026 and sold the program and its capsid and zinc finger platforms to Eli Lilly (USD 50 million; closed by 13 October 2026). Stage: preclinical; a 3-month GLP toxicology study found no ST-506-related adverse findings and the nonclinical program was described as supporting a clinical trial application.

Key facts

  • Ownership: Lilly acquired ST-506 and the platforms; Sangamo had expected a clinical trial application as early as mid-2026 before its Chapter 11.
  • Safety package (July 2026 slides): 3-month GLP toxicology, no ST-506-related adverse findings across 38 FDA-recommended tissues; survival prolonged in mice dosed after symptom onset.
  • Modality: AAV gene therapy delivering a zinc finger transcriptional repressor, intravenous with a blood-brain-barrier capsid.
  • Human data: None.
  • Limits: AAV delivery is irreversible and carries immune and off-target questions; preprint data not peer reviewed.

Timeline

  1. 2024Dose-dependent PRNP repression in non-human primates after IV delivery; CTA expected Q4 2025.
  2. 2025Preprint: more than 95 percent PRNP mRNA reduction in vitro; stable neuronal PrP lowering for at least 17 months in mice; greatly extended lifespan in infected mice even when given late; PRNP repression in monkeys with a blood-brain-barrier capsid.
  3. 2026Sangamo files Chapter 11 and signs the asset sale to Lilly.
  4. 2026Sangamo presents ST-506 data at a CJD Foundation event (slides hosted by the Foundation).
  5. 2026Lilly selected as successful bidder.
  6. 2026Sale reported closed.
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