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Cited by 3Virus-based gene therapy researchHerpesvirus Infections and TreatmentsRNA Interference and Gene Delivery

Herpes Simplex Virus Type 1/Adeno-Associated Virus Hybrid Vectors~!2009-12-12~!2010-01-13~!2010-06-17~!

de Oliveira, Anna Paula, Fraefel, Cornel·2010·The Open Virology Journal
DOI 10.2174/1874357901004030109
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Abstract

Herpes simplex virus type 1 (HSV-1) amplicons can accommodate foreign DNA of any size up to 150 kbp and, therefore, allow extensive combinations of genetic elements.Genomic sequences as well as cDNA, large transcriptional regulatory sequences for cell type-specific expression, multiple transgenes, and genetic elements from other viruses to create hybrid vectors may be inserted in a modular fashion.Hybrid amplicons use genetic elements from HSV-1 that allow replication and packaging of the vector DNA into HSV-1 virions, and genetic elements from other viruses that either direct integration of transgene sequences into the host genome or allow episomal maintenance of the vector.Thus, the advantages of the HSV-1 amplicon system, including large transgene capacity, broad host range, strong nuclear localization, and availability of helper virus-free packaging systems are retained and combined with those of heterologous viral elements that confer genetic stability to the vector DNA.Adeno-associated virus (AAV) has the unique capability of integrating its genome into a specific site, designated AAVS1, on human chromosome 19.The AAV rep gene and the inverted terminal repeats (ITRs) that flank the AAV genome are sufficient for this process.HSV-1 amplicons have thus been designed that contain the rep gene and a transgene cassette flanked by AAV ITRs.These HSV/AAV hybrid vectors direct site-specific integration of transgene sequences into AAVS1 and support long-term transgene expression.

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  • The 'targeted integration' approach can deliver very large transgenes (up to 150 kb).

    “Nonetheless, this 'targeted integration' approach, which can deliver very large transgenes (up to 150 kb) [114], remains an interesting tool worth further exploration.”

    From Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders (2022) · cites this paper as [114]

    The Abstract says HSV-1 amplicons accommodate up to 150 kbp of foreign DNA and that HSV/AAV hybrids retain their large transgene capacity. However, the section on site-specific integration reports integration of inserts of approximately 100 kb, with reduced efficiency; it does not establish targeted integration of a 150-kb transgene. No page number is available in our copy. (LLM, conf=0.83)

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Sorted by citations

Authors
de Oliveira, A. P., & Fraefel, C.
Affiliations
University of Zurich (CH)
ORCID
Fraefel, Cornel
Venue
The Open Virology Journal
Publisher
Bentham Science Publishers Ltd.
Published
2010-08-20
Volume
4
Issue
3
Pages
109-122
ISSN
1874-3579 (ISSN-L)
DOI
10.2174/1874357901004030109
OpenAlex
W2057715276
Cited by
3
References
5
Citations by year
2021: 1 · 2020: 1
FWCI
0.18
Type
journal article
Language
en
Open access
closed
Locations
The Open Virology Journal (publishedVersion)
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 type 1, adeno-associated virus, hybrid vectors, site-specific integration, inverted terminal repeats, episomal maintenance, transgene expression, viral vectors

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