This application note demonstrates how CNS-3D Brain Organoids can be applied for the accurate prediction of both ASO neurotoxicity and efficacy, enabling integrated assessment of functional tolerability and target knockdown in the same human model.

Key Takeaways:

ASO neurotoxicity prediction outperforms sequence-based and 2D methods

CNS-3D achieved 92% sensitivity and 92% specificity across a panel of 24 ASOs, outperforming sequence-based and 2D calcium methods while minimizing false positives.

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Clinical ASO assessment

CNS-3D Brain Organoids enable evaluation of ASO-mediated target knockdown alongside neurotoxicity in the same human organoid model.

Integrated safety and target activity assessment

Clinically approved ASOs nusinersen and tofersen showed low predicted acute neurotoxicity alongside measurable target knockdown in CNS-3D Brain Organoids.