Author Correction: Strategies to package recombinant Adeno-Associated Virus expressing the N-terminal gasdermin domain for tumor treatment

NATURE COMMUNICATIONS(2022)

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摘要
Pyroptosis induced by the N-terminal gasdermin domain (GSDM NT ) holds great potential for anti-tumor therapy. However, due to the extreme cytoxicity of GSDM NT , it is challenging to efficiently produce and deliver GSDM NT into tumor cells. Here, we report the development of two strategies to package recombinant adeno-associated virus (rAAV) expressing GSDM NT : 1) drive the expression of GSDM NT by a mammal specific promoter and package the virus in Sf9 insect cells to avoid its expression; 2) co-infect rAAV-Cre to revert and express the double-floxed inverted GSDM NT . We demonstrate that these rAAVs can induce pyroptosis and prolong survival in preclinical cancer models. The oncolytic-viruses induce pyroptosis and evoke a robust immune-response. In a glioblastoma model, rAAVs temporarily open the blood-brain barrier and recruit tumor infiltrating lymphocytes into the brain. The oncolytic effect is further improved in combination with anti-PD-L1. Together, our strategies efficiently produce and deliver GSDM NT into tumor cells and successfully induce pyroptosis, which can be exploited for anti-tumor therapy.
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关键词
Cancer immunotherapy,Cell death,Science,Humanities and Social Sciences,multidisciplinary
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