Herpes Simplex Virus Type 1/Adeno-Associated Virus Hybrid Vectors

Oliveira, Anna Paula de; Fraefel, Cornel

doi:10.2174/1874357901004010109

Cited by 5 publications

(4 citation statements)

References 242 publications

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“…This study also raises possibilities of designing both viral and non-viral vectors with LEDGF/p75 fusion proteins targeting safer genomic sites. Hybrid HSV/AAV vectors have been constructed in an attempt to combine the large insert cloning capacity of non-integrating HSV vectors (up to 150 kb) with the site-specific integration property of AAV vectors into a genomic hotspot, the AAVS1 locus, and to a certain extent, randomly (De Oliveira & Fraefel, 2010). Other HSV-based hybrid vectors include the episomally maintained HSV/EBV and randomly integrating HSV/RV vectors.…”

Section: Novel and Hybrid Viral Vectorsmentioning

confidence: 99%

Recent Advances and Improvements in the Biosafety of Gene Therapy

Sivalingam¹,

Kon²

2011

Gene Therapy - Developments and Future Perspectives

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Introduction 1.1 Overview of gene therapy Progress in understanding the cellular and molecular bases of human health and disease in recent decades has spawned research in the fields of regenerative medicine and gene therapy. These novel approaches to medical treatments offer new possibilities of mitigating, and even curing, a plethora of medical conditions ranging from rare inherited monogenic disorders, metabolic diseases, infections and even complex disorders such as cancer. In a simplified form, gene therapy can be defined as any procedure aimed at genetically altering or modifying cells or tissues with exogenous genetic materials that encompasses RNA, DNA and even oligonucleotides. These molecules may be directly delivered, in vivo into patients, often with the goal of targeting particular tissues (or organs). Alternatively, patients' cells may be isolated, expanded and modified ex vivo before reimplantation into the same subject (figure 1). Whilst gene therapy appears to be a relatively new concept in the field of biomedicine, the original conceptualization of treating diseases by genetic engineering dates back as early as the 1940s. Avery, MacLeod and McCarthy pioneered the notion and demonstrated that genes could be transferred within nucleic acids (Avery et al., 1944). Early visionary investigators such as Tatum (Tatum, 1966) envisioned " that viruses will be effectively used for man's benefit, in theoretical studies in somatic-cell genetics and possibly in genetic therapy..." And at the end of that same decade, the earliest experimentation of gene delivery in humans was carried out controversially by Rogers and colleagues, who explored the idea of using Shope papilloma virus to treat three patients with arginase deficiency (Wolff & Lederberg, 1994). The decades that followed witnessed tremendous advances in recombinant DNA technology and enabled the first approved human gene therapy clinical trial in 1990 for treating infants with adenosine deaminase deficiency (Blaese et al., 1995). By the turn of the millennium, almost 4000 patients had received gene therapy from more than 500 clinical trials worldwide (Scollay, 2001), albeit with varying and limited successes. Nonetheless, these trials were helpful in highlighting several aspects of gene therapy that demanded improvements and refinements to achieve meaningful therapeutic efficacy and patient safety. www.intechopen.com Recent Advances and Improvements in the Biosafety of Gene Therapy Recent Advances and Improvements in the Biosafety of Gene Therapy Recent Advances and Improvements in the Biosafety of Gene Therapy Recent Advances and Improvements in the Biosafety of Gene Therapy 157 Recent Advances and Improvements in the Biosafety of Gene Therapy

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Section: Novel and Hybrid Viral Vectorsmentioning

confidence: 99%

Recent Advances and Improvements in the Biosafety of Gene Therapy

Sivalingam¹,

Kon²

2011

Gene Therapy - Developments and Future Perspectives

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Section: Novel and Hybrid Viral Vectorsmentioning

confidence: 99%

Gene Therapy - Developments and Future Perspectives

Kang¹

2011

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Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published articles. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book.

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“…For example, plasmid-based HSV pseudoviral amplicon vectors show great promise in gene therapy and have been studied for several decades [25,26]. Studies have shown that long-term transgene expression can be achieved when the AAV rep gene is added along with the transgene of interest into the HSV-1 amplicon plasmid, with the transgene flanked with AAV inverted terminal repeat elements (ITRs) [27][28][29].…”

Section: Introductionmentioning

confidence: 99%

High-brightness anterograde transneuronal HSV1 H129 tracer modified using a Trojan horse-like strategy

Ying

Han

et al. 2020

Mol Brain

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Neurotropic viral transsynaptic tracing is an increasingly powerful technique for dissecting the structure and function of neural circuits. Herpes simplex virus type 1 strain H129 has been widely used as an anterograde tracer. However, HSV tracers still have several shortcomings, including high toxicity, low sensitivity and non-specific retrograde labeling. Here, we aimed to construct high-brightness HSV anterograde tracers by increasing the expression of exogenous genes carried by H129 viruses. Using a Trojan horse-like strategy, a HSV/AAV (adenoassociated virus) chimaera termed H8 was generated to enhance the expression of a fluorescent marker. In vitro and in vivo assays showed that the exogenous gene was efficiently replicated and amplified by the synergism of the HSV vector and introduced AAV replication system. H8 reporting fluorescence was brighter than that of currently available H129 tracers, and H8 could be used for fast and effective anterograde tracing without additional immunostaining. These results indicated that foreign gene expression in HSV tracers could be enhanced by integrating HSV with AAV replication system. This approach may be useful as a general enhanced expression strategy for HSV-based tracing tools or gene delivery vectors.

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Herpes Simplex Virus Type 1/Adeno-Associated Virus Hybrid Vectors

Cited by 5 publications

References 242 publications

Recent Advances and Improvements in the Biosafety of Gene Therapy

Recent Advances and Improvements in the Biosafety of Gene Therapy

Gene Therapy - Developments and Future Perspectives

High-brightness anterograde transneuronal HSV1 H129 tracer modified using a Trojan horse-like strategy

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