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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity
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Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity

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

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摘要

The design of highly defective herpes simplex virus (HSV) vectors for transgene expression in nonneuronal cells in the absence of toxic viral-gene activity has been elusive. Here, we report that elements of the latency locus protect a nonviral promoter against silencing in primary human cells in the absence of any viral-gene expression. We identified a CTCF motif cluster 5' to the latency promoter and a known long-term regulatory region as important elements for vigorous transgene expression from a vector that is functionally deleted for all five immediate-early genes and the 15-kb internal repeat region. We inserted a 16.5-kb expression cassette for full-length mouse dystrophin and report robust and durable expression in dystrophin-deficient muscle cells in vitro. Given the broad cell tropism of HSV, our design provides a nontoxic vector that can accommodate large transgene constructs for transduction of a wide variety of cells without vector integration, thereby filling an important void in the current arsenal of gene-therapy vectors.

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