文章：

腺相关病毒递送成孔蛋白Gasdermin-D的神经鞘瘤基因治疗

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

原文发布日期：2019-01-09 

英文摘要：

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.

摘要翻译： 

施万细胞瘤是一种周围神经鞘肿瘤，与三种遗传学上截然不同的疾病实体相关，即散发性神经鞘瘤、2型神经纤维瘤病和神经鞘瘤病。该疾病可导致严重功能障碍，甚至危及生命。手术切除是主要治疗手段，但其本身可能引起神经损伤，且因肿瘤位置特殊有时无法实施。鉴于该肿瘤由同质的施万细胞系组成，它成为基因治疗的理想靶点。本研究构建了一种基于腺相关血清型1病毒（AAV1）的载体，该载体在施万细胞特异性启动子P0调控下递送焦亡基因Gasdermin-D的N端片段（GSDMDNterm）。我们证实，将AAV1-P0-GSDMDNterm注射至坐骨神经内施万细胞瘤后，不仅能抑制肿瘤生长、消除肿瘤相关疼痛，还不会引起神经损伤。这种AAV1-P0-GSDMDNterm载体有望通过直接瘤内注射的方式为施万细胞瘤的临床治疗提供新方案。

原文链接：

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