TS-005619 — 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.

TS-005616 — This new invention is a Schwann cell-specific promoter that allows detailed, selective gene expression in Schwann cells while maintaining compatibility with AAV vectors, a limitation found in the current promoter systems for Schwann cells. Not only will this address a major field-wide barrier, but is also applicable to gene therapies for demyelinating neuropathies, including CMT1A, CMT4, CMTX, NF1, NF2, and inflammatory or injury-associated Schwann-cell disorders. Additionally, this invention will allow an optimized AAV9-KDAR expression cassette for CMT1B, incorporating the lead SSP. This finalized therapeutic construct will be ready for in vivo evaluation in our CMT1B mouse models, enabling selection of the lead candidate for subsequent IND-enabling studies and progression toward clinical translation.

TS-002174 — Currently, no cure exists for Charcot-Marie tooth type 1B (CMT1B). Inventors and specialists in Gene Therapy at Nationwide Children’s Hospital invented a methodology along with sequences for using microRNAs (miRNA) to inhibit and replace abnormal expressions of the myelin protein zero (MPZ) gene. Affecting 1 in 30,000 people, CMT1B is caused by more than 200 mutations of the MPZ, the essential protein needed for a healthy and efficient peripheral nervous system. The accumulation of mutant MPZ genes will result in, but not limited to, muscle weakness, atrophy, lost of sensation in the lower legs and feet and sensory loss.