Schwann-Tropic AAV

This new gene-delivery platform optimization for safe and efficient transduction of Schwann cells in the peripheral nervous system addresses the barriers in treating demyelinating neuropathies such as Charcot‑Marie‑Tooth disease (CMT1A, CMT1B, CMT4, CMT‑X), neurofibromatosis, and Multiple Sclerosis (MS). Through the combination of several capsid engineering strategies to enhance the tropism of adeno-associated virus (AAV) vectors for Schwann cells. Using barcodes ancestral AAV libraries that enable systematic identification of structural capsid motifs associated with Schwann‑cell targeting, in combination with peptide, DARPin, or nanobody insertions at key capsid regions, VRVIII, VRIV, and the VP2 N‑terminus, to enhance Schwann‑cell receptor binding and blood‑nerve‑barrier penetration. This platform produces novel capsid variants that achieve dramatically improved Schwann‑cell tropism at lower vector doses, reducing systemic and liver exposure.

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