Replication-competent herpes simplex vectors: design and applications

Argnani, Rafaela; Lufino, Michele M. P.; Manservigi, Marco; Manservigi, Roberto

doi:10.1038/sj.gt.3302622

Cited by 21 publications

(10 citation statements)

References 67 publications

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“…A number of different HSV-1 recombinant viruses have been constructed and evaluated for their ability to treat a variety of different cancers in animal models, as well as in human phase I/II clinical trials (Todo, 2002;Hu and Coffin, 2003;Argnani et al, 2005;Shen and Nemunaitis, 2006). Tumor volumes were measured before (negative values on the x axis) and after the injections.…”

Section: Discussionmentioning

confidence: 99%

Effective Treatment of Human Breast Tumor in a Mouse Xenograft Model with Herpes Simplex Virus Type 1 Specifying the NV1020 Genomic Deletion and the gBsyn3 Syncytial Mutation Enabling High Viral Replication and Spread in Breast Cancer Cells

Israyelyan

Melancon²,

Lomax³

et al. 2007

Human Gene Therapy

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A new oncolytic and fusogenic herpes simplex virus type 1 (HSV-1) was constructed on the basis of the wildtype HSV-1(F) strain. To provide for safety and tumor selectivity, the virus carried a large deletion including one of the two alpha4, gamma(1)34.5, alpha0 genes and the latency-associated transcript region. The gamma(1)34.5 gene, a major neurovirulence factor, was replaced by a gene cassette constitutively expressing the red fluorescent protein gene. Homologous recombination was used to transfer the fusogenic gBsyn3 mutation to the viral genome to produce the OncSyn virus. OncSyn causes extensive virus-induced cell fusion (syncytia) and replicates to higher titers than the parental Onc and HSV-1(F) strains in breast cancer cells. Biochemical analysis revealed that the OncSyn virus retains a stable genome and expresses all major viral glycoproteins. A xenograft mouse model system using MDA-MB-435S-luc (MM4L) human breast cancer cells constitutively expressing the luciferase gene implanted within the interscapular region of animals was used to test the ability of the virus to inactivate breast tumor cells in vivo. Seventy-two mice bearing MM4L breast cancer xenografts were randomly divided into three groups and given two rounds of three consecutive intratumoral injections of OncSyn, inactivated OncSyn, or phosphate-buffered saline 3 days apart. A single round of virus injections resulted in a drastic reduction of tumor sizes (p

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Section: Discussionmentioning

confidence: 99%

Effective Treatment of Human Breast Tumor in a Mouse Xenograft Model with Herpes Simplex Virus Type 1 Specifying the NV1020 Genomic Deletion and the gBsyn3 Syncytial Mutation Enabling High Viral Replication and Spread in Breast Cancer Cells

Israyelyan

Melancon²,

Lomax³

et al. 2007

Human Gene Therapy

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“…At the present time, there are viral and non-viral vectors. Adenovirus, Herpes simplex virus, Lentiviruses, Retroviruses and Adeno-associated virus is among the most popular viral vectors[ 76 77 78 79 80 81 ] and Naked DNA, Cationic liposomes, Minimalistic immunologically defined gene expression vectors as well as Polyethylenimines and Polyamidoamine dendrimers are among the non-viral biologic methods. [ 81 82 83 ]…”

Section: Techniquementioning

confidence: 99%

Gene therapy in keratoconus

2015

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Keratoconus (KC) is the most common ectasia of the cornea and is a common reason for corneal transplant. Therapeutic strategies that can arrest the progression of this disease and modify the underlying pathogenesis are getting more and more popularity among scientists. Cumulating data represent strong evidence of a genetic role in the pathogenesis of KC. Different loci have been identified, and certain mutations have also been mapped for this disease. Moreover, Biophysical properties of the cornea create an appropriate candidate of this tissue for gene therapy. Immune privilege, transparency and ex vivo stability are among these properties. Recent advantage in vectors, besides the ability to modulate the corneal milieu for accepting the target gene for a longer period and fruitful translation, make a big hope for stupendous results reasonable.

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“…Additionally, HSV-1 activates TLR2 for induction of pro-inflammatory cytokines and TLR9 for induction of type I interferons [ 38 • ]. Both replication-competent and incompetent vectors have been developed [ 39 , 40 ]. While replication-competent herpesvirus vectors are advantageous in many applications for their persistence, replication-deficient hervesvirus vaccine vectors also induce durable immune responses [ 38 • ].…”

Section: Herpesvirusmentioning

confidence: 99%

Replicating and non-replicating viral vectors for vaccine development

Robert-Guroff

2007

Current Opinion in Biotechnology

238

208

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IntroductionHistorically, live attenuated, replicating vaccines, rather than inactivated preparations, have provided the most effective protection against viral infection and disease. A partial list of such vaccines includes measles, mumps, rubella, polio, vaccinia, and yellow fever [1]. Notably, these vaccines elicit essentially life-long protective immunity. In contrast, immunity induced by inactivated or subunit vaccines is generally of more limited duration. A key factor in pursuit of the latter approaches is safety. Concerns arise not only over the possibility of disease induction in vaccinated individuals, particularly those who are immune compromised, but also over spread of the vaccine virus in the population. These issues are perhaps most evident in the efforts to develop a vaccine against HIV, where the target populations are likely to include some individuals already infected with HIV and perhaps immune suppressed as a result of their infection. Yet, nowhere is the urgency of vaccine development greater than in the AIDS field. In this chapter replicating and non-replicating viral vectors will be discussed with the focus largely on AIDS vaccine research, where a spectrum of both types of vector, each with its own unique advantages and disadvantages, is under development. Review of several in each category will illustrate issues faced in vector selection.Viral vectors for which both replicating and non-replicating forms are available include adenoviruses and poxviruses. Vectors designed primarily as replication-defective include adeno-associated virus, alphavirus, and herpesvirus, while replicating vectors include measles virus and vesicular stomatitis virus. Other vectors based on very successful vaccines have been less heavily exploited and will not be covered here. For example, poliovirus and yellow fever virus vaccines, both replication-competent, elicit life-long, persistent immunity. Yet as vectors, both exhibit not only genetic instability but also small insert capacity [2], limiting interest for vaccine development. Features of various viral vectors and recent results following their use will first be reviewed followed by a consideration of issues faced in vector selection. Table 1 lists some of the properties of each of the vectors covered here. Replicating and Non-replicating Adenovirus VectorsAdenoviruses (Ad) are among the most heavily exploited vectors for vaccine development. The virology and molecular biology of the double-stranded DNA virus were heavily investigated for years as part of gene therapy applications, providing an invaluable knowledge base for further development in the vaccine arena. Several Ad features are particularly attractive for vaccine use, including infection of both dividing and non-dividing cells, high levels of Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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Replication-competent herpes simplex vectors: design and applications

Cited by 21 publications

References 67 publications

Effective Treatment of Human Breast Tumor in a Mouse Xenograft Model with Herpes Simplex Virus Type 1 Specifying the NV1020 Genomic Deletion and the gBsyn3 Syncytial Mutation Enabling High Viral Replication and Spread in Breast Cancer Cells

Effective Treatment of Human Breast Tumor in a Mouse Xenograft Model with Herpes Simplex Virus Type 1 Specifying the NV1020 Genomic Deletion and the gBsyn3 Syncytial Mutation Enabling High Viral Replication and Spread in Breast Cancer Cells

Gene therapy in keratoconus

Replicating and non-replicating viral vectors for vaccine development

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