Intracellular delivery of oncolytic viruses with engineered Salmonella causes viral replication and cell death

Shradha Khanduja; Shoshana M K Bloom; Vishnu Raman; Chinmay P Deshpande; Christopher L Hall; Neil S Forbes

doi:10.1016/j.isci.2024.109813

Intracellular delivery of oncolytic viruses with engineered Salmonella causes viral replication and cell death

iScience. 2024 Apr 25;27(6):109813. doi: 10.1016/j.isci.2024.109813. eCollection 2024 Jun 21.

Authors

Shradha Khanduja¹, Shoshana M K Bloom¹, Vishnu Raman¹, Chinmay P Deshpande¹, Christopher L Hall¹, Neil S Forbes^{1

2

3}

Affiliations

¹ Department of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA.
² Molecular and Cell Biology Program, University of Massachusetts, Amherst, Amherst, MA, USA.
³ Institute for Applied Life Science, University of Massachusetts, Amherst, Amherst, MA, USA.

Abstract

As therapies, oncolytic viruses regress tumors and have the potential to induce antitumor immune responses that clear hard-to-treat and late-stage cancers. Despite this promise, clearance from the blood prevents treatment of internal solid tumors. To address this issue, we developed virus-delivering Salmonella (VDS) to carry oncolytic viruses into cancer cells. The VDS strain contains the PsseJ-lysE delivery circuit and has deletions in four homologous recombination genes (ΔrecB, ΔsbcB, ΔsbcCD, and ΔrecF) to preserve essential hairpins in the viral genome required for replication and infectivity. VDS delivered the genome for minute virus of mice (MVMp) to multiple cancers, including breast, pancreatic, and osteosarcoma. Viral delivery produced functional viral particles that are cytotoxic and infective to neighboring cells. The release of mature virions initiated new rounds of infection and amplified the infection. Using Salmonella for delivery will circumvent the limitations of oncolytic viruses and will provide a new therapy for many cancers.

Keywords: Bacteriology; Cell biology; Microbiology; Virology.