Infectious Recombinant Senecavirus A Expressing p16INK4A Protein

Abstract

Senecavirus A (SVA) is an oncolytic RNA virus, and it is the ideal oncolytic virus that can be genetically engineered for editing. However, there has not been much exploration into creating SVA viruses that carry antitumor genes to increase their oncolytic potential. The construction of SVA viruses carrying antitumor genes that enhance oncolytic potential has not been fully explored. In this study, a recombinant SVA-CH-01-2015 virus (p15A-SVA-clone) expressing the human p16INK4A protein, also known as cell cycle-dependent protein kinase inhibitor 2A (CDKN2A), was successfully rescued and characterized. The recombinant virus, called SVA-p16, exhibited similar viral replication kinetics to the parent virus, was genetically stable, and demonstrated enhanced antitumor effects in Ishikawa cells. Additionally, another recombinant SVA virus carrying a reporter gene (iLOV), SVA-iLOV, was constructed and identified using the same construction method as an auxiliary validation. Collectively, this study successfully created a new recombinant virus, SVA-p16, that showed increased antitumor effects and could serve as a model for further exploring the antitumor potential of SVA as an oncolytic virus.

Engineering Non-Human RNA Viruses for Cancer Therapy

“…Importantly, SVV has demonstrated anti-tumor capacity when administered systemically, leading to an extent of survival in an orthotopic medulloblastoma cancer model [63]. eSVV's reverse genetics have allowed the insertion of exogenous therapeutic payloads that can enhance the oncolytic activity of SVV-001 [66]. In the study conducted by Wencheng et al, an oncolytic SVV-A codifying p16 INK4A protein, also known as cell cycle-dependent protein kinase inhibitor 2A (CDKN2A), was rescued and characterized [66].…”

“…eSVV's reverse genetics have allowed the insertion of exogenous therapeutic payloads that can enhance the oncolytic activity of SVV-001 [66]. In the study conducted by Wencheng et al, an oncolytic SVV-A codifying p16 INK4A protein, also known as cell cycle-dependent protein kinase inhibitor 2A (CDKN2A), was rescued and characterized [66]. The results showed that SVA-p16 had significantly stronger antitumor effects than the unmodified SVA virus in the human oligodendroglioma Ishikawa cell line.…”