Virion-Associated Cofactor High-Mobility Group DNA-Binding Protein-1 Facilitates Transposition from the Herpes Simplex Virus/<i>Sleeping Beauty</i>Amplicon Vector Platform

Silva, Suresh de; Lotta, Louis T.; Burris, Clark A.; Bowers, William J.

doi:10.1089/hum.2010.022

Cited by 11 publications

(5 citation statements)

References 25 publications

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“…Thus, overexpression of HMGB1 by gene transfection has the ability to enhance SB-mediated transposition efficiency, which provides a novel DNA transposition system for gene transfer (Zayed et al, 2004). Besides the SB system, HMGB1 has the ability to enhance other DNA transposition systems such as herpes simplex virus/Sleeping Beauty (HSV/SB) amplicon vector platform (de Silva et al, 2010; Peterson et al, 2007). These findings make HMGB1 an excellent candidate for improving gene transfer in gene therapy.…”

Section: Hmgb1 Functionmentioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

822

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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Section: Hmgb1 Functionmentioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

822

828

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“…Electroporation (Johnen et al, 2012), transfection reagents (Belur et al, 2007), and hydrodynamic injection (Bell et al, 2007) do not appear to be effective methods of delivering transposon elements in the anterior segment. To address this problem, a hybrid vector combining a chimeric virus and transposons has been developed (de Silva et al, 2010). EGFP expression was seen in RPE, corneal endothelial, and iris cells after subretinal injection of such hybrid vector in mice (Turunen et al, 2014).…”

Section: Non-viral Gene Deliverymentioning

confidence: 99%

Gene transfer to the outflow tract

Dang

Loewen

Parikh

et al. 2017

Experimental Eye Research

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Elevated intraocular pressure is the primary cause of open angle glaucoma. Outflow resistance exists within the trabecular meshwork but also at the level of Schlemm's canal and further downstream within the outflow system. Viral vectors allow to take advantage of naturally evolved, highly efficient mechanisms of gene transfer, a process that is termed transduction. They can be produced at biosafety level 2 in the lab using protocols that have evolved considerably over the last 15 to 20 years. Applied by an intracameral bolus, vectors follow conventional as well as uveoscleral outflow pathways. They may affect other structures in the anterior chamber depending on their transduction kinetics which can vary among species when using the same vector. Not all vectors can express long-term, a desirable feature to address the chronicity of glaucoma. Vectors that integrate into the genome of the target cell can achieve transgene function for the life of the transduced cell but are mutagenic by definition. The most prominent long-term expressing vector systems are based on lentiviruses that are derived from HIV, FIV, or EIAV. Safety considerations make non-primate lentiviral vector systems easier to work with as they are not derived from human pathogens. Non-integrating vectors are subject to degradation and attritional dilution during cell division. Lentiviral vectors have to integrate in order to express while adeno-associated viral vectors (AAV) often persist as intracellular concatemers but may also integrate. Adeno- and herpes viral vectors do not integrate and earlier generation systems might be relatively immunogenic. Nonviral methods of gene transfer are termed transfection with few restrictions of transgene size and type but often a much less efficient gene transfer that is also short-lived. Traditional gene transfer delivers exons while some vectors (lentiviral, herpes and adenoviral) allow transfer of entire genes that include introns. Recent insights have highlighted the role of non-coding RNA, most prominently, siRNA, miRNA and lncRNA. SiRNA is highly specific, miRNA is less specific, while lncRNA uses highly complex mechanisms that involve secondary structures and intergenic, intronic, overlapping, antisense, and bidirectional location. Several promising preclinical studies have targeted the RhoA or the prostaglandin pathway or modified the extracellular matrix. TGF-β and glaucoma myocilin mutants have been transduced to elevate the intraocular pressure in glaucoma models. Cell based therapies have started to show first promise. Past approaches have focused on the trabecular meshwork and the inner wall of Schlemm's canal while new strategies are concerned with modification of outflow tract elements that are downstream of the trabecular meshwork.

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“…In contrast, K562 cells that have been one of the most successful cell lines for SB -mediated transposition achieving rates as high as 60% of cells expressing the DsRed reporter gene following Tn integration. Interestingly, we characterized the expression of transcript encoding the host co-factor HMGB1, which has been shown to be rate limiting for SB -mediated transposition [Zayed et al, 2003; de Silva et al, 2010]. The levels of HMGB1 mRNA were substantially lower in the BOECs than K562 cells, suggesting that HMGB1 might be a rate limiting factor for transposition.…”

Section: Discussionmentioning

confidence: 99%

β‐globin matrix attachment region improves stable genomic expression of the Sleeping beauty transposon

Sjeklocha

Chen

Daly

et al. 2011

J of Cellular Biochemistry

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The liver is an attractive target for gene therapy due to its extensive capability for protein production and the numerous diseases resulting from a loss of gene function it normally provides. The Sleeping Beauty Transposon (SB-Tn)1 system is a non-viral vector capable of delivering and mediating therapeutic transgene(s) insertion into the host genome for long-term expression. A current challenge for this system is the low efficiency of integration of the transgene. In this study we use a human hepatoma cell line (HuH-7) and primary human blood outgrowth endothelial cells (BOECs) to test vectors containing DNA elements to enhance transposition without integrating themselves. We employed the human β-globin matrix attachment region (MAR) and the Simian virus 40 (SV40) nuclear translocation signal to increase the percent of HuH-7 cells persistently expressing a GFP::Zeo reporter construct by ~50% for each element; while combining both did not show an additive effect. Interestingly, both elements together displayed an additive effect on the number of insertion sites, and in BOECs the SV40 alone appeared to have an inhibitory effect on transposition. In long-term cultures the loss of plasmid DNA, transposase expression and mapping of insertion sites demonstrated bona fide transposition without episomal expression. These results show that addition of the β-globin MAR and potentially other elements to the backbone of SB-Tn system can enhance transposition and expression of therapeutic transgenes. These findings may have a significant influence on the use of SB transgene delivery to liver for the treatment of a wide variety of disorders.

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

Cited by 11 publications

References 25 publications

HMGB1 in health and disease

HMGB1 in health and disease

Gene transfer to the outflow tract

β‐globin matrix attachment region improves stable genomic expression of the Sleeping beauty transposon

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