Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity

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Abstract
Significance: Gene therapy has made significant strides in the treatment and even cure of single-gene defects. However, the maturation of this field will require more sophisticated vehicles capable of cell-selective delivery of large genetic payloads whose regulated expression will restore or enhance cellular functionality. High-capacity herpes simplex virus vectors have the potential to meet these challenges but have been limited by the need to preserve one particularly cytotoxic viral product, infected cell polypeptide 0, to maintain transgene transcriptional activity. Our study describes a vector design that solves this conundrum, thereby promising the near-term availability of viral vectors that can efficiently deliver large or multiple regulated transgenes to a diversity of cells without attendant cytotoxicity.
Funding Information
  • HHS | NIH | National Institute of Neurological Disorders and Stroke (NS064988)
  • HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK044935)
  • CHDI Foundation (A3777)

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