Targeting the Central Nervous System with Herpes Simplex Virus / Sleeping Beauty Hybrid Amplicon Vectors
Open accessAbstract
The pursuits of sustainable treatments for diseases and disorders that afflict the central nervous system (CNS) have proven challenging for the field of viral vector-based gene therapy. However, recent advances in viral vector technology coupled with efficient delivery methods have opened up new avenues that show promise at the preclinical testing stage. The development of the Herpes Simplex Virus/Sleeping Beauty (HSV/SB) hybrid vector represents such an advance for devising treatments targeting the CNS with its potential for stably integrating large transgenomic segments of DNA within the genomes of transduced cells. In utero administration of this hybrid vector into the embryonic mouse brain has revealed the capacity for widespread transgene dissemination due to the targeting of a neuronal precursor cell population. This unique feature has provided the means to stably express a transgene throughout the brain for prolonged periods, which is a prerequisite for the treatment of progressive CNS disorders. In this review we provide a comprehensive breakdown of the characteristics of the HSV/SB vector system and how it can be efficiently employed in the derivation of CNS-targeted gene therapeutic strategies.
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Because wild-type HSV causes encephalitis, developing nontoxic replication-defective vectors with deletions in the IE genes (ICP4, ICP22, ICP27) is essential.
“However, because wild-type HSV causes encephalitis, developing nontoxic replication-defective vectors with deletions in the IE genes (ICP4, ICP22, ICP27) 114 is essential.”
From Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges (2020) · cites this paper as [114]
HSV vectors containing latency-active promoters LAP1 and LAP2 have been engineered for long-term expression (up to 300 days) in the peripheral nervous system.
“HSV vectors containing latency-active promoters LAP1 and LAP2 have been engineered for long-term expression (up to 300 days) in the peripheral nervous system.”
From Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges (2020) · cites this paper as [114]
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Research works printed but not linked: 2
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Ghosh, S., Brown, A. M., Jenkins, C., & Campbell, K. (2020) · Applied Biosafety · doi:10.1177/1535676019899502 · Cited by 218 · see citing works
- Authors
- de Silva, S., & J. Bowers, W.
- Venue
- Current Gene Therapy
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2011-10-01
- Volume
- 11
- Issue
- 5
- Pages
- 332-340
- ISSN
- 1566-5232 (ISSN-L)
- PMC
- PMC4141986
- OpenAlex
- W2084188282
- Cited by
- 20
- References
- 63
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 5
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (NIH R01-AG023593, R01AG023593)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- herpes simplex virus, Sleeping Beauty transposon, CNS gene therapy, neuronal precursors, transgene integration, embryonic mouse brain, central nervous system disorders
- MeSH terms
- Animals, Blindness, Brain, Central Nervous System Diseases, Genetic Vectors, Humans, Genetic Therapy, Genome, Human, Simplexvirus, Gene Targeting, Transgenes, Transposases, Mice, Neural Stem Cells
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