ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Viral and cellular insulators promote sustained HSV vector-mediated transgene expression in brain.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Modular Scalable Synthetic Gene Circuits for Complex Functions Within Minimal Computational Layers in Human Cells.Nature communications · 2026Article
- Next-generation replication-defective HSV vectors for delivery of large DNA payloads.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
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Authors and funding
3 authors.
Funding
Abstract
We have developed a gene therapy platform based on non-toxic, high-capacity replication-defective (rd) herpes simplex virus type 1 (HSV-1) vectors. We previously determined that transgene expression from rdHSV-1 vectors requires strategic placement of insulators-small DNA elements that overcome the host's epigenetic silencing of foreign DNA-to maintain transgenes in euchromatin regions. Transgene expression was rescued by replacing either the latency associated transcript (LAT) or the the infected cell protein 4 (ICP4) gene with the transgene cassette close to naturally occurring viral insulators. The ICP4 locus was more permissive for transgene expression than the LAT locus in neurons in vitro. Following in vivo brain delivery, transgene expression from both loci lasted for at least 4 months. However, the level of expression tended to decline over time. To enhance transgene expression, we designed a novel insulator environment by combining cellular insulators with the resident viral insulators. In combination, these elements provided significantly higher levels of transgene expression in the brain than the viral insulators alone, lasting for at least 11.7 months. This new cassette design extends transgene activity in neurons compared with previous designs and holds promise for gene therapy applications in treating brain disorders.
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Registered trials
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