Viral vectors for gene therapy and gene modification approaches

Merten, Otto‐Wilhelm; Gaillet, Bruno

doi:10.1016/j.bej.2015.09.005

Cited by 38 publications

(25 citation statements)

References 169 publications

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“…Self-aggregating 1.8 kDa polyethylenimines with dissolution switch at endosomal acidic pH are delivery carriers for plasmid DNA, mRNA, siRNA and exon-skipping oligonucleotides Manuela Chiper, 1,2 Nassera Tounsi, 2,3 Ryszard Kole, 4 Antoine Kichler, 2,5,6 and Guy…”

Section: Appendix a Supplementary Datamentioning

confidence: 99%

“…Nucleic acids are attractive compounds for modulating the cell function with high precision but their poor efficacy in crossing the cell-protective plasma membrane limit their ability to reach the intracellular site of action [1][2][3][4][5]. Modified viruses are on the frontline of DNA delivery for gene therapy [6,7] but they cannot directly deliver synthetic versions of mRNA, siRNA or oligonucleotides which may exhibit superior activity and minimal immune or toxic response. Some synthetic nucleic acids, administrated alone, were shown to alleviate muscle [8] or liver pathologies [9] but only a small portion of the injected nucleic acids still reaches the cell cytoplasm and/or nucleus.…”

Section: Introductionmentioning

confidence: 99%

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Self-aggregating 1.8 kDa polyethylenimines with dissolution switch at endosomal acidic pH are delivery carriers for plasmid DNA, mRNA, siRNA and exon-skipping oligonucleotides

Chiper

Tounsi

Kole

et al. 2017

Journal of Controlled Release

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Efficiency of polyethylenimine (PEI) for nucleic acid delivery is affected by the size of the carrier and length of the nucleic acids. For instance, PEIs with molecular weights between 10-30kDa provide optimal DNA delivery activity whereas PEIs with molecular weights below 1.8kDa are ineffective. The activity of PEI is also severely diminished by substitution of DNA for shorter nucleic acids such as mRNA or siRNA. Here, through chemical modification of the primary amines to aromatic domains we achieved nucleic acid delivery by the 1.8kDa polyethylenimine (PEI) particles. This modification did not affect the PEI buffering abilities but enhanced its pH-sensitive aggregation, enabling stabilization of the polyplex outside the cell while still allowing nucleic acid release following cellular entry. The aromatic PEIs were then evaluated for their gene, mRNA, siRNA and 2'O-methyl phosphorothioate oligonucleotide in vitro transfection abilities. The salicylamide-grafted PEI showed to be a reliable carrier for delivering nucleic acids with cytoplasmic activity such as the mRNA and siRNA or nuclear diffusible oligonucleotide. It was then further equipped with polyethyleneglycol (PEG) and the delivery efficiency of the copolymer was tested in vivo for regeneration of dystrophin in the muscle of mdx mouse through a 2'O-methyl phosphorothioate-mediated splicing modulation. Intramuscular administration of polyplexes resulted in dystrophin-positive fibers in a mouse model of Duchenne muscular dystrophy without apparent toxicity. These findings indicate that precise modifications of low molecular weight PEI improve its bio-responsiveness and yield delivery vehicles for nucleic acids of various types in vitro and in vivo.

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Section: Appendix a Supplementary Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Self-aggregating 1.8 kDa polyethylenimines with dissolution switch at endosomal acidic pH are delivery carriers for plasmid DNA, mRNA, siRNA and exon-skipping oligonucleotides

Chiper

Tounsi

Kole

et al. 2017

Journal of Controlled Release

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“…Specific productivity for AAV is in the range of 10 3 to 10 6 particles/cell with cell densities three‐ to hundred‐fold lower. For further details about BEVS, please refer to the following recent reviews .…”

Section: Introductionmentioning

confidence: 99%

Manufacturing of recombinant adeno‐associated viruses using mammalian expression platforms

Robert

Chahal

Audy

et al. 2017

Biotechnology Journal

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Manufacturing practices for recombinant adeno-associated viruses (AAV) have improved in the last decade through the development of new platforms in conjunction with better production and purification methods. In this review, we discuss the advantages and limitations of the most popular systems and methods employed with mammalian cell platforms. Methods and systems such as transient transfection, packaging and producer cells and adenovirus and herpes simplex virus are described. In terms of best production yields, they are comparable with about 10 -10 vector genomes produced per cell but transient transfection of HEK293 cells is by far the most commonly used. For small-scale productions, AAV can be directly purified from the producing cell lysate by ultracentrifugation on a CsCl or iodixanol-step gradient whereas large-scale purification requires a combination of multiple steps. Micro/macrofiltration (i.e. including tangential flow filtration and/or dead-end filtration) and chromatography based-methods are used for large-scale purification. Purified AAV products must then be quantified and characterized to ensure quality. Recent purification methods and current analytical techniques are reviewed here. Finally, AAV technology is very promising, but manufacturing improvements are still required to meet the needs of affordable, safe and effective AAV vectors essential for licensing of gene therapy clinical protocols.

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“…However, the main disadvantage of nonviral gene vectors remains their low transfection efficiency (Ibraheem, Elaissari, & Fessi, 2014;Wang, Upponi, & Torchilin, 2012). In contrast, adenovirus vectors have high transfection efficiency for different quiescent and dividing cell types (He et al, 1998;Merten & Gaillet, 2016) and have been shown to be useful in tissue engineering (Benest et al, 2006; S. L. Li, Liu, & Hui, 2015). The adenovirus-mediated gene transfer of VEGF and Ang-1 stimulated different angiogenic phenotypes to enhance functional neovascularization in adult tissue (Benest et al, 2006).…”

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confidence: 99%

Silk fibroin scaffolds loaded with angiogenic genes in adenovirus vectors for tissue regeneration

Wang

Jiang

et al. 2019

J Tissue Eng Regen Med

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Vascularization remains a critical challenge in dermal tissue regeneration. In this study, a vascular endothelial growth factor (VEGF165) and angiopoietin‐1 (Ang‐1) dual gene coexpression vector that encoded green fluorescent protein (GFP) was constructed from an arginine–glycine–aspartic acid‐modified adenovirus. Silk fibroin (SF) scaffolds loaded with adenovirus vectors were fabricated by freeze‐drying method. In vitro, the human endothelial‐derived cell line EA.hy926 was infected with adenovirus vectors and then expressed GFP, secreted VEGF165 and Ang‐1, and promoted cell proliferation effectively. The VEGF165 and Ang‐1 genes loaded in the SF scaffolds significantly promoted the formation of abundant microvascular networks in the chick embryo chorioallantoic membrane. In vivo, angiogenic genes loaded in the scaffolds promoted vascularization and collagen deposition in scaffolds, thus effectively accelerating dermal tissue regeneration in a dorsal full‐thickness skin defect wound model in Sprague–Dawley rats. In conclusion, SF scaffolds loaded with arginine–glycine–aspartic acid‐modified adenovirus vectors encoding VEGF165 and Ang‐1 could stimulate the formation of vascular networks through the effective expression of target genes in vascular endothelial cells, thereby accelerating the regeneration of dermal tissue.

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Viral vectors for gene therapy and gene modification approaches

Cited by 38 publications

References 169 publications

Self-aggregating 1.8 kDa polyethylenimines with dissolution switch at endosomal acidic pH are delivery carriers for plasmid DNA, mRNA, siRNA and exon-skipping oligonucleotides

Self-aggregating 1.8 kDa polyethylenimines with dissolution switch at endosomal acidic pH are delivery carriers for plasmid DNA, mRNA, siRNA and exon-skipping oligonucleotides

Manufacturing of recombinant adeno‐associated viruses using mammalian expression platforms

Silk fibroin scaffolds loaded with angiogenic genes in adenovirus vectors for tissue regeneration

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