Update on herpesvirus amplicon vectors

Oehmig, Angelika; Fraefel, Cornel; Breakefield, Xandra O.

doi:10.1016/j.ymthe.2004.06.641

Cited by 59 publications

(45 citation statements)

References 145 publications

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“…We therefore set out to further characterize the effect of Rep on the replication of HSV-1. As a global measure of HSV-1 replication efficiency, we employed a previously described HSV-1 amplicon packaging assay (1,59,64). Briefly, Vero 2-2 cells, which express HSV-1 ICP27 from its native promoter (72), were transfected with an HSV-1 amplicon plasmid encoding EGFP, pHSVGFP, together with an HSV-1 helper bacterial artificial chromosome (BAC), fHSV⌬pac⌬27⌬kn, and an ICP27 expressing plasmid, pEBHICP27.…”

Section: Resultsmentioning

confidence: 99%

“…The HSV-1 helper BAC fHSV⌬pac⌬27⌬kn consists of an HSV-1 genome with the ICP27 gene and pac deleted (the nonessential ␥ 1 34.5 gene is also deleted due to deletion of pac). In the presence of trans-expressed ICP27, the HSV-1 helper BAC represents a replication-competent, packagingdefective HSV-1 genome providing helper functions for replication and packaging of HSV-1 amplicon plasmids (59,64). Although Vero 2-2 cells express ICP27, the cotransfection of an ICP27-expressing plasmid is required for high titers of HSV-1 amplicon vector stocks (64).…”

Section: Resultsmentioning

confidence: 99%

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Inhibition of Herpes Simplex Virus Type 1 Replication by Adeno-Associated Virus Rep Proteins Depends on Their Combined DNA-Binding and ATPase/Helicase Activities

Glauser

Seyffert

Strasser

et al. 2010

J Virol

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Adeno-associated virus (AAV) has previously been shown to inhibit the replication of its helper virus herpes simplex virus type 1 (HSV-1), and the inhibitory activity has been attributed to the expression of the AAV Rep proteins. In the present study, we assessed the Rep activities required for inhibition of HSV-1 replication using a panel of wild-type and mutant Rep proteins lacking defined domains and activities. We found that the inhibition of HSV-1 replication required Rep DNA-binding and ATPase/helicase activities but not endonuclease activity. The Rep activities required for inhibition of HSV-1 replication precisely coincided with the activities that were responsible for induction of cellular DNA damage and apoptosis, suggesting that these three processes are closely linked. Notably, the presence of Rep induced the hyperphosphorylation of a DNA damage marker, replication protein A (RPA), which has been reported not to be normally hyperphosphorylated during HSV-1 infection and to be sequestered away from HSV-1 replication compartments during infection. Finally, we demonstrate that the execution of apoptosis is not required for inhibition of HSV-1 replication and that the hyperphosphorylation of RPA per se is not inhibitory for HSV-1 replication, suggesting that these two processes are not directly responsible for the inhibition of HSV-1 replication by Rep.Adeno-associated virus (AAV) is a widespread, nonpathogenic human parvovirus with a unique biphasic life cycle. In the absence of a helper virus, AAV establishes a latent infection in the host cell mediated either by site-specific integration of the viral genome into human chromosome 19 or by episomal persistence of circularized virus genomes (reviewed in reference 53). In the presence of helper viruses such as a herpesvirus, adenovirus (Ad), or papillomavirus, AAV is rescued from latency and undergoes lytic replication. The AAV genome is a single-stranded DNA (ssDNA) of 4,680 nucleotides, which is packaged into an icosahedral capsid with a diameter of 20 nm. The AAV genome harbors two open reading frames (ORFs), rep and cap, which are flanked by two inverted terminal repeats (ITRs) containing viral origins of DNA replication. The cap ORF is transcribed from the p40 promoter and encodes the capsid proteins VP1, VP2, and VP3, which differ in their N termini due to alternative start codons. The rep ORF encodes the Rep proteins, which are expressed in four different forms due to transcription from two different promoters, p5 and p19, and alternative splicing at an intron at the C-terminal end. The different Rep proteins are termed Rep40, Rep52, Rep68, and Rep78 according to their apparent molecular weight. The Rep proteins are involved in diverse processes in the viral life cycle, such as DNA replication, regulation of gene expression, genome packaging, and site-specific integration (reviewed in reference 56). The biochemical activities of Rep required for AAV DNA metabolism include site-specific DNA-binding and endonuclease activities, as well as non-site-sp...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Inhibition of Herpes Simplex Virus Type 1 Replication by Adeno-Associated Virus Rep Proteins Depends on Their Combined DNA-Binding and ATPase/Helicase Activities

Glauser

Seyffert

Strasser

et al. 2010

J Virol

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“…In addition, the factors controlling longterm in vivo expression are also being elucidated (Burton et al, 2005;Tyler et al, 2006). For example, hybrid HSV amplicon vectors that combine features of other viral vectors that allow long-term transgene expression but retain the large cDNA packaging capacity of HSV are being investigated (Oehmig et al, 2004a;Oehmig et al, 2004b). HSV's inherent neural tropism, retrograde transport, and large transgene capacity are attractive features to be exploited in the future.…”

Section: Herpes Simplex Virus (Hsv)mentioning

confidence: 99%

Viral vectors for in vivo gene transfer in Parkinson's disease: Properties and clinical grade production

Mandel

Bürger

Snyder

2008

Experimental Neurology

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Because Parkinson's disease is a progressive degenerative disorder that is mainly confined to the basal ganglia, gene transfer to deliver therapeutic molecules is an attractive treatment avenue. The present review focuses on direct in vivo gene transfer vectors that have been developed to a degree that they have been successfully used in animal model of Parkinson's disease. Accordingly, the properties of recombinant adenovirus, recombinant adeno-associated virus, herpes simplex virus, and lentivirus are described and contrasted. In order for viral vectors to be developed into clinical grade reagents, they must be manufactured and tested to precise regulatory standards. Indeed, clinical lots of viral vectors can be produced in compliance with current Good Manufacturing Practices (cGMPs) regulations using industry accepted manufacturing methodologies, manufacturing controls, and quality systems. The viral vector properties themselves combined with physiological product formulations facilitate long-term storage and direct in vivo administration.

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“…W ith a packaging capacity of approximately 130 kb and an ability to efficiently transduce numerous cell types, the herpes simplex virus type 1 (HSV-1) amplicon provides an attractive modality for gene therapeutic applications (Spaete and Frenkel, 1982;Oehmig et al, 2004). The HSV amplicon contains two noncoding elements from the wild-type HSV-1 genome, which are the packaging/cleavage site ( pac) and the HSV-1 origin of replication (oriS), and is devoid of all viral genes.…”

Section: Introductionmentioning

confidence: 99%

Virion-Associated Cofactor High-Mobility Group DNA-Binding Protein-1 Facilitates Transposition from the Herpes Simplex Virus/Sleeping BeautyAmplicon Vector Platform

et al. 2010

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The development of the integration-competent, herpes simplex virus/Sleeping Beauty (HSV/SB) amplicon vector platform has created a means to efficiently and stably deliver therapeutic transcription units (termed ''transgenons'') to neurons within the mammalian brain. Furthermore, an investigation into the transposition capacity of the HSV/SB vector system revealed that the amplicon genome provides an optimal substrate for the transposition of transgenons at least 12 kb in length [de Silva, S., Mastrangelo, M.A., Lotta, L.T., Jr., Burris, C.A., Federoff, H.J., and Bowers, W.J. (2010). Gene Ther. 17, 424-431]. These results prompted an investigation into the factors that may contribute toward efficient transposition from the HSV/SB amplicon. One of the cellular cofactors known to play a key role during SB-mediated transposition is the high-mobility group DNA-binding protein-1 (HMGB1). Our present investigation into the role of HMGB1 during amplicon-based transposition revealed that transposition is not strictly dependent on the presence of cellular HMGB1, contrary to what had been previously demonstrated with plasmid-based SB transposition. We have shown for the first time that during amplicon preparation, biologically active HMGB1 derived from the packaging cell line is copackaged into amplicon vector particles. As a result, HSV/SB amplicon virions arrive prearmed with HMGB1 protein at levels sufficient for facilitating SB-mediated transposition in the transduced mammalian cell.

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Update on herpesvirus amplicon vectors

Cited by 59 publications

References 145 publications

Inhibition of Herpes Simplex Virus Type 1 Replication by Adeno-Associated Virus Rep Proteins Depends on Their Combined DNA-Binding and ATPase/Helicase Activities

Inhibition of Herpes Simplex Virus Type 1 Replication by Adeno-Associated Virus Rep Proteins Depends on Their Combined DNA-Binding and ATPase/Helicase Activities

Viral vectors for in vivo gene transfer in Parkinson's disease: Properties and clinical grade production

Virion-Associated Cofactor High-Mobility Group DNA-Binding Protein-1 Facilitates Transposition from the Herpes Simplex Virus/Sleeping BeautyAmplicon Vector Platform

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