Intracellular trafficking of nonviral vectors

Medina-Kauwe, Lali K.; Xie, Jun

doi:10.1038/sj.gt.3302592

Cited by 312 publications

(262 citation statements)

References 226 publications

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“…They include cellular binding and subsequent internalization, transfer from endosome into cytosol (endosomal escape), nuclear entry, and gene transcription [11,12]. Therefore, to achieve efficient transfection of DCs, vectors must be rationally designed specifically for DC to pass through these cellular processes efficiently.…”

Section: Introductionmentioning

confidence: 99%

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Gene delivery to dendritic cells mediated by complexes of lipoplexes and pH-sensitive fusogenic polymer-modified liposomes

Yuba

Kojima

Sakaguchi

et al. 2008

Journal of Controlled Release

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Section: Introductionmentioning

confidence: 99%

“…Therefore, to achieve efficient transfection of DCs, vectors must be rationally designed specifically for DC to pass through these cellular processes efficiently. Among these cellular processes, efficient cellular binding and endosomal escape greatly affect the efficiency of non-viral vector-mediated transfection [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Gene delivery to dendritic cells mediated by complexes of lipoplexes and pH-sensitive fusogenic polymer-modified liposomes

Yuba

Kojima

Sakaguchi

et al. 2008

Journal of Controlled Release

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“…The uptake of complexes by HEK293 cells is expected to occur through the clathrin-dependent endocytosis, which is a prevalent way of macromolecule transport into mammalian cells [27]. Based on existing reports on Pluronic-mediated transfection, one can suggest similar mechanisms for promoting cellular uptake in the presence of TFCs, in particular, the stabilization of pDNA complexes in serum-containing culture medium [9] and the stimulation of endocytic activity [10].…”

Section: Cellular Uptake Of Plasmid Dna Complexes In the Presence Of mentioning

confidence: 99%

Intracellular delivery of VEGF165 encoding gene therapeutic using trifunctional copolymers of ethylene oxide and propylene oxide

Bondar

Shevchenko

Мартынова

et al. 2015

European Polymer Journal

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New type of copolymers of propylene oxide and ethylene oxide was assessed for promoting delivery of plasmid DNA based gene therapeutics. Lipid-like trifunctional copolymers (TFCs), with both random or diblock structures and relatively low hydrophilic-lipophilic balance, were studied and compared with linear Pluronic™ L61. Structure-dependent relationships for micelleforming, cytotoxic and hemolytic properties of these copolymers were revealed. The TFC with the mean number of propylene oxide and ethylene oxide units of 83.5 and 24.2, respectively, exhibited relatively low adverse effects in vitro. The latter TFC interacted with plasmid DNApolyethyleneimine complexes and improved their intracellular delivery. Furthermore, this TFC efficiently promoted the transfection of dermal fibroblasts with VEGF165-encoding Neovasculgen® plasmid DNA, which has been clinically used for the therapeutic angiogenesis.Our findings demonstrated for the first time that TFCs are promising for the polymer-mediated delivery of gene therapeutics.

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“…18,19 Most non-viral vectors, including lipoplexes, are now accepted to be internalized through endocytosis, where binding to or association with surface receptors through specific or nonspecific interactions activates intracellular signaling pathways that promote endocytosis. 17 Evidence for endocytosis rests largely on the dependence of internalization on temperature, time, concentration, and energy. 20,21 Confocal and electron microscopy studies confirm internalization via endocytosis, showing complexes in intracellular vesicles suggestive of endosomes.…”

Section: Mechanisms Of Complex Internalizationmentioning

confidence: 99%

“…Recent reviews have consolidated these findings, detailing transfection capabilities for numerous non-viral vectors. 16,17 This review takes a stepwise approach to comparing the abilities of non-viral vectors to overcome specific transfection obstacles relative to viruses, correlating individual processes with demonstrated transfection efficiencies. In particular, this review focuses on factors affecting specific stages in the transfection process: (1) internalization (usually endocytosis), (2) intracellular trafficking, (3) escape to the cytosol, (4) nuclear translocation, and (5) gene transcription/expression.…”

Section: Introductionmentioning

confidence: 99%

Toward Development of Artificial Viruses for Gene Therapy: A Comparative Evaluation of Viral and Non‐viral Transfection

Douglas¹

2008

Biotechnology Progress

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Problems related to the safety and efficacy of gene therapies have checked the enthusiasm once surrounding this field, though it remains a promising approach for the treatment of numerous diseases. Despite the high transfection efficiencies attainable using viral vectors, manufacturing difficulties, safety concerns, and limitations related to targeting and plasmid size have prompted considerable research into the development of non‐viral vectors. Non‐viral vectors demonstrate low toxicity, low immunogenicity, and ease of manufacture. However, they have not yet achieved the transfection efficiencies displayed by viruses. The inability to explain or predict transfection efficiencies results, in part, from insufficient understanding of the intracellular processes involved in gene delivery. Increasingly, research has been undertaken to probe the processes involved in overcoming the major obstacles to vector‐mediated transfection: (1) internalization, (2) intracellular trafficking, (3) escape to the cytosol, (4) nuclear translocation, and (5) gene transcription/expression. This paper reviews and compares the pathways and techniques involved in successful viral and non‐viral transfection. In addition, this review provides evidence that non‐viral vector development has been pursued successfully thus far, producing systems capable of evading almost all major obstacles to transfection. Evaluating the abilities of non‐viral and viral vectors to overcome specific cellular barriers reveals that the greatest advantage of viral vectors may be related to viral DNA, which is transcribed considerably more efficiently than plasmid DNA. Further study in this area should enable the development of non‐viral vectors that transfect as efficiently as viral vectors.

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Intracellular trafficking of nonviral vectors

Cited by 312 publications

References 226 publications

Gene delivery to dendritic cells mediated by complexes of lipoplexes and pH-sensitive fusogenic polymer-modified liposomes

Gene delivery to dendritic cells mediated by complexes of lipoplexes and pH-sensitive fusogenic polymer-modified liposomes

Intracellular delivery of VEGF165 encoding gene therapeutic using trifunctional copolymers of ethylene oxide and propylene oxide

Toward Development of Artificial Viruses for Gene Therapy: A Comparative Evaluation of Viral and Non‐viral Transfection

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