The Generative Brain

Whitehead Institute and MIT (Weissman lab)

Whitehead Institute (Cambridge, Massachusetts), where Jonathan Weissman's lab built CHARM, the compact epigenetic editor that silences the prion protein gene in mouse brain.

Key facts

  • Whitehead scientist Jonathan Weissman co-led the CHARM work with Sonia Vallabh of the Broad.
  • Co-first authors Edwin Neumann (graduate student) and Tessa Bertozzi (postdoc) are from the Weissman lab.
  • A single intravenous AAV dose eliminated more than 80 percent of brain PrP in mice and the paper appeared in Science on 28 June 2024.
  • The CHARM design replaces Cas9 with a zinc finger protein and recruits the cell's own DNMT3A, with a self-silencing feature.
  • Delivery across the mouse brain depends on an engineered AAV capsid from the Broad lab of Ben Deverman.

Timeline

  1. 2024Deverman lab delivery vector published.
  2. 2024CHARM published in Science.
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