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Schwannoma gene therapy by adeno-associated virus delivery of the pore-forming protein Gasdermin-D

Cancer Gene Therapy (2019) | Download Citation


Schwannomas are peripheral nerve sheath tumors associated with three genetically distinct disease entities, namely sporadic schwannoma, neurofibromatosis type-2, and schwannomatosis. Schwannomas are associated with severe disability and in cases lead to death. The primary treatment is operative resection that itself can cause neurologic damage and is at times contra-indicated due to tumor location. Given their homogenous Schwann-lineage cellular composition, schwannomas are appealing targets for gene therapy. In the present study, we have generated an adeno-associated serotype 1 virus (AAV1)-based vector delivering N-terminal of the pyroptotic gene Gasdermin-D; (GSDMDNterm) under the control of the Schwann-cell specific promoter, P0. we have demonstrated that AAV1-P0-GSDMDNterm injection into intra-sciatic schwannomas reduces the growth of these tumors and resolves tumor-associated pain without causing neurologic damage. This AAV1-P0-GSDMDNterm vector holds promise for clinical treatment of schwannomas via direct intra-tumoral injection.

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We thank Dr. Marco Giovannini, M.D., Ph.D. (UCLA Health) for the HEI-193 and 08031-9 cell lines, and Timothy Houle, Ph.D. (Department of Anesthesia, Critical Care and Pain Medicine, MGH) for his assistance with statistical analysis.


This work was supported by NIH/NINDS R01 NS081146, NIH/NINDS tR21 NS088013, and a charitable donation from Neurofibromatosis Northeast to the Rebecca Grasso Fund.

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  1. Department of Anesthesiology, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA

    • Sherif G. Ahmed
    • , Abdelanabi Ahmed
    • , Mohamed Doha
    •  & Gary J. Brenner


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The authors declare that they have no conflict of interest.

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Correspondence to Gary J. Brenner.

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