Further improvements in the technology of HSV-1-based amplicon vectors

Abstract

Background: Herpes simplex virus type 1 (HSV-1) amplicon vectors can be used to deliver transgenes to the nuclear environment of mammalian cells without cytotoxicity or pathogenic consequences for the inoculated organisms. Previous efforts describe a method of making helper virus-free amplicons (hf-HSV particles) or cells that contain those particles (e.g., packaging cell lines or patient's cells infected in vivo or ex vivo). Objective/methods: Described herein are several advances in hf-HSV particle technology that were designed to improve both production, by expressing viral proteins in trans (e.g., virion host shutoff protein and/or viral protein 16) during production, and also amplicon genome expression stability in the infected cells, by including a transposon-encoding system (e.g., the Tcl-like Sleeping Beauty transposon system). Results/conclusions: Improved titers and chromosomal integration of the transgene enhanced hf-HSV amplicon applications. Nevertheless, further studies will be needed to improve the safety of treatments using an integrating amplicon vector.

Keywords::

• cancer therapy
• gene therapy
• hearing loss
• hf-HSV particle
• HSV-1 accessory proteins
• HSV-1 amplicons
• neurological applications
• Sleeping Beauty transposons
• vaccination

Acknowledgments

The authors thank Kyle Grant for critical reading of the manuscript.