In order to optimize gene delivery and regulation, a single viral vector ensuring. Here, qualification of the relevant manufacturers, good supply chain control, and additional testing contribute to another level of complexity. Clinical trials using recombinant adenoassociated virus raav vectors have demonstrated efficacy and a good safety profile. The goal of the vvc is to provide investigators at umms with the most suitable and efficient gene transfer vectors for their research applications. Recombinant viral vector biosafety levels stanford. Ideally, these vectors should be produced at high titer and purity with. While baculoviruses normally infect insect cells, recombinant baculoviruses can serve as genetransfer vehicles for transient expression of recombinant proteins in a wide range of mammalian cell types. Review of sv40 contamination of polio vaccine pdf,569kb. The simian virus 40 polyadenylation signal sv40 polya has been routinely inserted downstream of the polyhedrin promoter in many baculovirus expression vector systems bevs.
Simian virus 40 sv40 dna is generally used as a mammalian vector. Hansen, new mexico state university, united states of. It is a shuttle vector, containing cole1 ori and sv40 origin 2. After the discovery of sv40s tumorigenic and cell transformation properties, a wave of studies in the 1960s and 1970s pursued the identification of viral oncogenic agents in humans. Establishment of five immortalized human ovarian surface. Simian virus 40 infection of humans pubmed central pmc. Viral vector core facility 500 newton road 221 eckstein medical research building iowa city, ia 52242 phone. This page is informational only this vector is not available from addgene please contact the manufacturer for further details. Viral vector vaccines carry an expression cassette encoding the vaccine antigen within their genome. Sv40 infects a wide range of cell types from humans and other mammals, and expresses its genes in them. The sv40derived vector, svaw, which encodes a variable fragment antibody recognizing.
Viral expression cassette elements to enhance transgene. Thus, sv40 origin of replication allows autonomous as an episome replication in mammalian cells expressing the sv40 large tantigen, such as cos7. Nevertheless, it may be virtually impossible to rule out such connection. A viral plasmids have been engineered such that they can be delivered to a host and generate virus right, similar to how natural viruses can be delivered to a host and generate virus left. Injection of piggybac vector into hemophilia a mice resulted in stable and sustained expression of fulllength fviii and. The ifn production after the virus infection was very high in monkey kidney cells, but less so in human epithelial cells, and low in mouse, pig, hamster cells and in human lymphocytes. Sv40based in vitro packaging vectors show great promise for use in gene therapy applications.
Vectors have been engineered based on aav, adenoviruses, alphaviruses, herpes simplex. Soon after the virus enters the cell, the cells own synthetic machinery recognizes a tata sequence at the center of the sv40 regulatory regions, shown in. Click on the links to view the plasmid collections. Three ptracer mammalian expression vectors are available that express gfp fused to the selectable marker zeocin.
Lentiviral vectors lvs are gene delivery vehicles for the genetic modification of mammalian cells. Gene therapy using a simian virus 40derived vector inhibits the. Sv40transfected bsc1 cells were freeze thawed three times 5 days posttransfection. They integrate into the host cell genome, providing a stable, long term expression of the gene of interest goi sequence with very low genotoxic potential. Lentiviral vectors to probe and manipulate the wnt signaling. However, stable transformants with sv40 based plasmids are difficult to obtain, since. The nucleotide sequence files available below are those used to produce the plasmid vector, viral and bacteriophage maps contained in new england biolabs catalog as well as the tables containing the locations of sites. Vector database is a digital collection of vector backbones assembled from publications and commercially available sources. Table i provides an overview of the testing required for cell banks, viral vector, and celltherapy product. Duke viral vector core duke university bryan research building, rm.
Pdf the influence of sv40 polya on gene expression of. Pdf factors influencing the production of recombinant sv40. Dec 14, 2015 the influence of sv40 polya on gene expression of baculovirus expression vector systems article pdf available in plos one 1012. Investigators should consult their institutions biosafety committee, or similar advisory body, before engaging in the production or manipulation of any form of viral gene delivery vector. It is strongly recommended you download this document to your own computer and open from there. The new vector system we developed is based on recombinant simian virus sv 40 rsv40, large t.
The viral vector core vvc of the gene therapy center uses cuttingedge technologies to create and produce a variety of high quality viral vectors. Viral vector vaccines are by definition infectious vaccines, as production of the vaccine antigen is achieved in situ upon infection of cells. Pdf simian virus 40 sv40 is a monkey virus that was administered to human. Duke viral vector core duke university bryan research building, 311 research drive, dumc box 3209. Pdf most gene therapy approaches employ viral vectors for gene delivery. Dec 14, 2015 schematic diagram of viral constructs with and without sv40 polya signals for egfp gene expression under the acmnpv polh promoter control at the polh, egt and gp37 loci of acmnpv genome to test the functions of sv40 polya in the baculovirus expression vector system. The viral stock contained no detectable wildtype sv40.
Although gene therapy seems to be feasible using recombinant viruses. Control optogenetic and other constructs no mta required, unless specified otherwise. Novel viral vector improves gene therapy for sickle cell disease. The influence of sv40 polya on gene expression of baculovirus expression vector systems article pdf available in plos one 1012. Sv40 dna was detected on rare occasions, usually in brain tumors, using relatively lowsensitivity southern hybridization techniques, immunostaining for lt, and.
In animal studies, adenoviral vectors require abl2 containment. Sv40 t antigencontaining cells should not be considered more hazardous than the intact virus. Get a printable copy pdf file of the complete article 964k, or click on a page image below to. Viral vectors are tailored to their specific applications but generally share a few key properties. During the past 4 years, polymerase chain reaction pcr assays have detected dna sequences related to sv40 an oncogenic simian polyomavirus in a variety of human tissues, especially choroid plexus tumors, ependymomas, mesotheliomas, and osteosarcomas 17. As part of that effort, we supply carefully annotated files for common plasmids. Regulated gene delivery systems are usually made of two elements. Sv40 based in vitro packaging vectors show great promise for use in gene therapy applications.
Rd simian virus 40 sv40 vectors could be an attractive alternative. Sv40 vector with early gene replacement efficient in. The present invention provides sv40based viral vectors for use in the delivery of genes to target cells. The crude viral supernatant was collected 48 h and 72 h after transfection collected viral medium, 10 ml. Today virus products are being used at higher titres than in the past and there is a greater potential for virus to be shed into the environment. Each vector uses a different set of promoters to express the gene of interest and the cycle 3 gfpzeocin fusion. Introduction the cis acting elements that regulate transgene expression can have as great of an impact on the success of gene therapy as the design of the vector capsid or envelope. These combined dna sequence and map files can be opened with snapgene or the free snapgene viewer. The rationale for this approach was based on several important aspects of sv40 virus and its activity. How simian virus 40 hijacks the intracellular protein. Sv40 early promoter, rous sarcoma virus promoter, adenovirus major late promoter, or human cytomegalovirus promoter 3. At the university of iowa, all varieties of viral vectors produced at the viral vector core are required to be handled at biosafety level 2 bsl2.
Sv40 persists as a latent infection in kidney, cns and circulating lymphocytes and transmission is thought to occur through direct contact with virus shed in urine simon et al. Some viral vectors are based on attenuated viruses, such as vaccinia virus. Vaccine contamination with sv40 occurred in the united states between 1955 and 1961 simian vacuolating virus 40, known as sv40, is a virus found in monkeys and humans, which has the potential to cause cancer, mainly in animals, although research indicates that it doesnt cause cancer in humans. To obtain the bjmu12tzeo vector, the sh ble gene, which was used to confer resistance to zeocin, and an sv40 polya signal were cloned pylin after the sv40 promoter of the bjmu vector, then 12 copies of trna. Simian virus 40 sv40, a possible human polyomavirus. Supervero cells produce similar numbers of sv40 vector parti cles compared to. These findings were supported by the isolation of infectious sv40 from a choroid plexus tumor. Oct 21, 2018 like other types of viral vectors, hpv and pyv based pseudoviruses represent a potential biohazard. The maps, notes, and annotations in the zip file on this page are ed material. Publications should acknowledge the donor of the reagent and the viral vector core at duke university.
Practical utilization of recombinant aav vector reference. Simian virus 40 sv40 is a nonenveloped, double stranded dna virus in the polyomavirus genus of the family papovaviridae, which also includes the bk and jc polyomaviruses of humans. Vector manufacturing and testing for gene and cell therapy. Among the viruses used as gene delivery vectors, the macaque. Consequently, we devised a gene transfer system based on simian virus40 sv40 1 as a vector. B viral plasmids can be modified for research purposes such that, when delivered to a host, they give rise to viruses with modified viral genomes. Cells infected with an sv40 mirna mutant are more sensitive to tagspeci. Although the field is advancing quickly, vector analytics and harmonization of dosage units are still a limitation for commercialization. The race is on for a coronavirus vaccine, 70 candidates, 3 at human trial stage.
The viralcontaining supernatant was passed through 0. Simian virus 40 vectors for pulmonary gene therapy ncbi. Aav reference standard materials rsms can help ensure product safety by controlling the consistency of assays used to characterize. Thus, sv40 origin of replication allows autonomous as an episome replication in mammalian cells expressing the sv40 large tantigen, such as cos7 cells. Generation of a verobased packaging cell line to produce sv40. In this study, we investigated the ability of a piggybac vector to deliver fulllength fviii, both in cultured cells and in a mouse model. National institutes of health risk group escherichia coli all enteropathogenic, enterotoxigenic, enteroinvasive and strains bearing k1 antigen, including e. All three ptracer vectors have the following features. Simian virus 40 tt antigens and lamin ac small interfering.
Sv40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Although viral vectors are occasionally created from pathogenic viruses, they are modified in such a way as to minimize the risk of handling them. The university of iowa viral vector core facility is supported in part by the university of iowa holden comprehensive cancer center. Viral vector safety guidance bsds environmental health. A tssv40 based new mammalian plasmid vector and its copy. The tumors investigated included ependymoma, all brain cancers combined, osteosarcoma, and mesothelioma. Supervero cells produce similar numbers of sv40 vector particles compared to. Virus and vector shedding as part of clinical trial studies of virus gene therapy products or other live virus products there is a requirement to understand if and by how much the body sheds virus.
To detect vector dna peak fractions for sv40, jcv, bkv, and lpv capsid vector particles, 1. Other viral vector systems that can be used for overexpression of proteins include vectors based on baculovirus, vaccinia virus, and herpes simplex virus. It has mrna processing signals including polyadenylation signal and intervening sequences. Fuerer c, nusse r 2010 lentiviral vectors to probe and manipulate the wnt signaling pathway. Sv40, we recently conducted a large, longterm retrospective followup study of birth cohorts exposed or unexposed to sv40 contaminated poliovirus vaccine strickler et al. Sv40 simian virus40 has been demonstrated to provide a unique vector for gene. The unique combination of multiple viral systems provides for vectors with increased carrying capacity and extended host range when compared to normal sv40 vectors. After the discovery of sv40 s tumorigenic and cell transformation properties, a wave of studies in the 1960s and 1970s pursued the identification of viral oncogenic agents in humans. Attempting to open large pdf files over the internet within the browser window may cause problems. Replication incompetent sv40 vectors in which the viral tantigen is replaced by the gene of interest are produced in vivo in cells that supply. The authors, who work in the plant viral vectorology field, have bill dawson to thank in some way for their scientific pedigree, and they are honored that he contributed the opening chapter of this volume with the history of plant virus vector development. Delivery of fulllength factor viii using a piggybac.
Like other types of viral vectors, hpv and pyv based pseudoviruses represent a potential biohazard. Getting from here to there benchtobedside a term used to describe the process by which the results of research done in the laboratory are directly used to develop new ways to treat. Rd simian virus 40 sv40 vectors could be an attractive alternative to aav vectors for clinical gene therapy. Lentiviral vector technology lentiviral vector basics. Potential of recombinant sv40based vectors for gene therapy.
Yet the viral vector manufacturer does not directly control production of these materials. Dec 28, 2006 sv40transfected bsc1 cells were freeze thawed three times 5 days posttransfection. Schematic diagram of viral constructs with and without sv40 polya signals for egfp gene expression under the acmnpv polh promoter control at the polh, egt and gp37 loci of acmnpv genome to test the functions of sv40 polya in the baculovirus expression vector system. Jan, 2003 regulated gene delivery systems are usually made of two elements. Sv40 has been widely studied as a model eukaryotic virus, leading to many early discoveries in eukaryotic dna replication 1 and transcription. In the baculovirus prototype autographa californica multiple nucleopolyhedrovirus acmnpv, the polyhedrin promoter very late promoter transcribes its gene by a viral rna polymerase therefore there is no supporting. Sv40, we recently conducted a large, longterm retrospective followup study of birth cohorts exposed or unexposed to sv40contaminated poliovirus vaccine strickler et al. This material may be used without restriction by academic, nonprofit, and governmental entities, except that the source must be cited as. Please check with your institutions biosafety officer to confirm local requirements. Sv40 infects a wide range of cell types from humans and other mammals, and expresses its. Sv40 vectors carrying minimal sequence of viral origin with. More than 30 years of followup data were available.
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