Base editing may improve inherited nerve cell disease in mice and lab-grown patient cells

AAV-mediated base editing prolonged survival and preserved motor neurons in a transgenic mouse model of hereditary motor and sensory neuropathy.

• Base editing targets both gain- and loss-of-function mechanisms in hereditary motor neuron diseases.
• The P285L variant in the TRK-fused gene (TFG) is associated with hereditary motor and sensory neuropathy with proximal dominant involvement.
• The optimal adenine base editor was identified through comparison in patient-derived induced pluripotent stem cells.
• Subpial delivery of AAV vectors was used to evaluate the selected base editor in a mouse model.
• Treatment with base editing reduced TFG aggregation and suppressed neuronal death in neuromuscular organoids derived from HMSN-P iPSCs.

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