Enhanced gene expression promoted by the quantized folding of pDNA within polyplex micelles

Osada, Kensuke; Shiotani, Tomonori; Tockary, Theofilus A.; Kobayashi, Daigo; Oshima, Hiroki; Ikeda, Sorato; Christie, R. James; Itaka, Keiji; Kataoka, Kazunori

doi:10.1016/j.biomaterials.2011.09.046

Cited by 53 publications

(86 citation statements)

References 25 publications

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“…Alternatively, in the rod structure, the transcriptional process could proceed along the rod axis but might be interfered at the rod end because of the impaired integrity of double stranded structure of DNA. 26,30 These feasible mechanisms involved in the transcriptional process is consistent with the observation that toroidal structure has higher transcriptional efficacy than rod structure. Note that the method permits transportation of pDNA directly into cytoplasm of skeletal muscle cells, 24 skipping the usual intracellular tracking route of particulate systems via endosomal uptake; therefore the effect of the packaging structure on transcription efficacy, as demonstrated in cell-free system, can directly be evaluated in animal model.…”

Section: Resultssupporting

confidence: 81%

“…We previously reported the significant anti-tumor effect 25 by this administration method to the subcutaneous xenograft of an intractable pancreatic tumor using our intensively studied rod-structured PMs. 18,23,[26][27][28][29][30] Therefore, the attained further increased efficacy of transgene expression using toroidal structures compared to rod-like structures would address the appreciable potential of this toroid structure and thus it should be explored in future studies as a distinct toroid-structured gene delivery system.…”

Section: Resultsmentioning

confidence: 99%

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Toroidal Packaging of pDNA into Block Ionomer Micelles Exerting Promoted in Vivo Gene Expression

Osada

Chen

et al. 2015

Biomacromolecules

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Selectively spooling single plasmid DNA (pDNA), as a giant polyelectrolyte, into a nanosized toroidal structure or folding it into a rod-like structure has been accomplished by polyion complexation with block catiomers to form polymeric micelles in varying NaCl concentrations. The interactive potency between the pDNA and block catiomers was determined to play a critical role in defining the ultimate structure of the pDNA; the formation of toroidal or rod-like structures was achieved by complexation in 600 or 0 mM NaCl solutions, respectively. Compared with the rod-like structure, the toroidal structure possessed superior biological functions capable not only of elevating in vitro transcription but also of elevating in vivo gene transduction efficiency. This demonstrated the great utility of the toroidal pDNA packaging as a distinct structured gene carrier. Furthermore, the fact that the NaCl concentration at which the toroidal structure was specifically formed corresponds to seawater stimulates interest in this ordered nanostructure as a possible inherent structure for DNA.

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Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Toroidal Packaging of pDNA into Block Ionomer Micelles Exerting Promoted in Vivo Gene Expression

Osada

Chen

et al. 2015

Biomacromolecules

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“…2) consistent with our previously reported scheme in which pDNA was regularly folded through the interaction with PEG-polycation block copolymers 34 . The pDNA in the DPc-TPMs then exhibited unique morphological changes depending on the DPc/Asp(DET) ratio.…”

Section: Discussionsupporting

confidence: 80%

Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer

et al. 2014

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Nanocarriers responding to light have great potential for pinpoint therapy, and recent studies have revealed promising in vivo activity. However, light-selective gene transfer still remains challenging in the systemic application. Here we report systemic light-responsive nanocarriers for gene delivery developed through the sequential self-assembly of ABC-type triblock copolymer/DNA/dendrimeric photosensitizer, forming polyplex micelles with three-layered functional nanocompartments. The DNA-packaged core is covered by the photosensitizer-incorporated intermediate layer, which is encompassed by an outer shielding shell. This three-layered structure permits multistep photosensitizer and DNA delivery into a solid tumour by a systemic route: the shielding layer minimizes unfavourable interactions with blood components, and the photosensitizer is delivered to endo-/lysosomal membranes to facilitate light-selective cytoplasmic translocation of the micelles, accomplishing DNA delivery into the nucleus to exert gene expression. The polyplex micelles display 4100-fold photoenhanced gene expression in cultured cells and exhibit light-induced in vivo gene transfer in solid tumours following systemic administration.

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“…It has been suggested that hydrodynamic force could induce the transient opening of cellular membrane to permit pDNA to be internalized into cells, the subsequent localization of pDNA into the nucleus may be achieved via some mechanisms such as active nuclear import, cell division or transient opening of nuclear membrane, etc. More recently, it has been reported that the HLV injection of condensed pDNA was even more effective than naked pDNA in achieving nuclear transgene expression in skeletal muscle [24,25] [26]. Based on these reports, we hypothesized that the HLV injection technique might be useful for delivering pDNA into, not only the nucleus, but also mitochondria.…”

Section: Introductionmentioning

confidence: 97%

Localization of exogenous DNA to mitochondria in skeletal muscle following hydrodynamic limb vein injection

Yasuzaki

Yamada

Kanefuji

et al. 2013

Journal of Controlled Release

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ABSTRACT.Mitochondrial genetic disorders are a major cause of mitochondrial diseases. It is therefore likely that mitochondrial gene therapy will be useful for the treatment of such diseases. Here, we report on the possibility of mitochondrial gene delivery in skeletal muscle using hydrodynamic limb vein (HLV) injection. The HLV injection procedure, a useful method for transgene expression in skeletal muscle, involves the rapid injection of a large volume of naked plasmid DNA (pDNA) into the distal vein of a limb. We hypothesized that the technique could be used to deliver pDNA not only to nuclei but also mitochondria, since cytosolic pDNA that is internalized by the method may be able to overcome mitochondrial membrane. We determined if pDNA could be delivered to myofibrillar mitochondria by HLV injection by PCR analysis. Mitochondrial toxicity assays showed that the HLV injection had no influence on mitochondrial function. These findings indicate that HLV injection promises to be a useful technique for in vivo mitochondrial gene delivery.

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Enhanced gene expression promoted by the quantized folding of pDNA within polyplex micelles

Cited by 53 publications

References 25 publications

Toroidal Packaging of pDNA into Block Ionomer Micelles Exerting Promoted in Vivo Gene Expression

Toroidal Packaging of pDNA into Block Ionomer Micelles Exerting Promoted in Vivo Gene Expression

Three-layered polyplex micelle as a multifunctional nanocarrier platform for light-induced systemic gene transfer

Localization of exogenous DNA to mitochondria in skeletal muscle following hydrodynamic limb vein injection

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