Engineering HSV-1 Vectors for Gene Therapy

Goins, William F.; Huang, Shaohua; Hall, Bonnie L.; Marzulli, Marco; Cohen, Justus B.

doi:10.1007/978-1-4939-9814-2_4

Cited by 26 publications

(28 citation statements)

References 36 publications

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“…To avoid the non-specific tracing, the sampling time should be limited to 3 days or a shorter time postinfection. In addition to being developed as a tracing tool, HSV-based vectors carrying exogenous genes have long been explored for gene therapy applications [39][40][41]. The…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Herpes simplex virus is an enveloped virus with a dsDNA genome more than 150 kb in length, which is divided into long and short unique segments (U L and U S , respectively) and flanked by inverted repeated sequences (TR L /IR L and TR S / IR S ). 110 The HSV genome encodes approximately 90 genes, almost half of which are nonessential and can be eliminated in recombinant vectors. 111 Currently, gene delivery and gene therapy applications use 3 types of HSV vectors.…”

Section: Herpesviral Vectorsmentioning

confidence: 99%

Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges

Ghosh

Brown

Jenkins³

et al. 2020

Applied Biosafety

121

113

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Introduction: National Institutes of Health (NIH) defines gene therapy as an experimental technique that uses genes to treat or prevent disease. Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be effective and safe. Methods: Applications of viral vectors and nonviral gene delivery systems have found an encouraging new beginning in gene therapy in recent years. Although several viral vectors and nonviral gene delivery systems have been developed in the past 3 decades, no one delivery system can be applied in gene therapy to all cell types in vitro and in vivo. Furthermore, the use of viral vector systems (both in vitro and in vivo) present unique occupational health and safety challenges. In this review article, we discuss the biosafety challenges and the current framework of risk assessment for working with the viral vector systems. Discussion: The recent advances in the field of gene therapy is exciting, but it is important for scientists, institutional biosafety committees, and biosafety officers to safeguard public trust in the use of this technology in clinical trials and make conscious efforts to engage the public through ongoing forums and discussions.

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“…HSV vectors have been developed for human gene therapy of brain tumors, such as glioblastoma multiforme, and for conditions such as chronic pain (37–44). The greatest number of trials have been done for malignant brain tumors, where HSV vectors have been used to deliver prodrug‐activating enzymes, resulting in so‐called “suicide gene” therapy and in some cases resulting in the release of tumor‐specific antigens at a locus at which inflammation was triggered by the viral components of the vector (45–55).…”

Section: Established Gene Therapy Vector Approachesmentioning

confidence: 99%

The rapidly evolving state of gene therapy

Gruntman

Flotte

2018

FASEB j.

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Gene therapy is emerging as a viable option for clinical therapy of monogenic disorders and other genetically defined diseases, with approved gene therapies available in Europe and newly approved gene therapies in the United States. In the past 10 years, gene therapy has moved from a distant possibility, even in the minds of much of the scientific community, to being widely realized as a valuable therapeutic tool with wide‐ranging potential. The U.S. Food and Drug Administration has recently approved Luxturna (Spark Therapeutics Inc, Philadelphia, PA, USA), a recombinant adeno‐associated virus (rAAV) 2 gene therapy for one type of Leber congenital amaurosis 2 (1, 2). The European Medicines Agency (EMA) has approved 3 recombinant viral vector products: Glybera (UniQure, Amsterdam, The Netherlands), an rAAV vector for lipoprotein lipase deficiency; Strimvelis (Glaxo Smith‐Kline, Brentford, United Kingdom), an ex vivo gammaretrovirus‐based therapy for patients with adenosine deaminase‐deficient severe combined immune deficiency (ADA‐SCID); and Kymriah (Novartis, Basel, Switzerland), an ex vivo lentivirus‐based therapy to engineer autologous chimeric antigen‐receptor T (CAR‐T) cells targeting CD19–positive cells in acute lymphoblastic leukemia. These examples will be followed by the clinical approval of other gene therapy products as this field matures. In this review we provide an overview of the state of gene therapy by discussing where the field stands with respect to the different gene therapy vector platforms and the types of therapies that are available.— Gruntman, A. M., Flotte, T. R. The rapidly evolving state of gene therapy. FASEB J. 32, 1733–1740 (2018). http://www.fasebj.org

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Engineering HSV-1 Vectors for Gene Therapy

Cited by 26 publications

References 36 publications

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

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

Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges

The rapidly evolving state of gene therapy

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