*3.2. rQNestin34.5*

rQNestin34.5 is a an engineered oHSV based on F-strain HSV1 that expresses the neurovirulence factor ICP34.5 under a synthetic nestin promoter to drive robust tumor-selective viral replication [49]. In vivo experiments showed that the survival after symptom-onset of glioma-bearing animals was significantly prolonged after treatment with rQNestin34.5 compared to controls including the previous generation of oHSV [49]. rQNestin34.5v2 is a derivative that lacks a fusion ICP6-GFP transcript [50] and is currently under investigation in a phase I clinical trial for recurrent glioblastoma in combination with cyclophosphamide (NCT03152318). Chiocca et al. [50] showed that rQNestin34.5v2 is selectively cytotoxic for glioma cells and conducted toxicologic analyses to determine a starting dose of <sup>1</sup> <sup>×</sup> <sup>10</sup><sup>6</sup> pfu for use in humans.
