Cell cycle dependence of gene transfer by lipoplex, polyplex and recombinant adenovirus

Brunner, Sylvia; Sauer, Thomas; Carotta, Sebastian; Cotten, Matthew; Saltik, Mediyha; Wagner, Ernst

doi:10.1038/sj.gt.3301102

Cited by 481 publications

(355 citation statements)

References 30 publications

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“…24,25 However, in spite of significant increase, they were not able to transfect the entire population of cells compared to the results obtained for photochemically enhanced adenovirus-mediated gene delivery. 26 By relying on the idea that the effectiveness of nonviral transfection systems depends on the cell cycle status, 27 they investigated the role of the cell cycle status in photochemical transfection mediated by two types of synthetic transfection agents: a cationic polypeptide polylysine (polyfection) and a cationic lipid formulation N-(2-amino ethyl)-N,N-dimethyl-2,3-bis(tetradecyloxy)-1-propanaminium bromide/dioleoylphosphatidyl ethanol amine. 28 The effect of photochemical treatment on EGFP expression in cells illuminated in different cell cycle phases was compared.…”

Section: Intelligent Polymeric Vectors In Gene Therapymentioning

confidence: 99%

Intelligent polymers as nonviral vectors

2005

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The successful gene therapy largely depends on the vector type that allows a selective and efficient gene delivery to target cells with minimal toxicity. Nonviral vectors are much safer and cheaper, can be produced easily in large quantities, and have higher genetic material carrying capacity. However, they are generally less efficient in delivering DNA and initiating gene expression as compared to viral vectors, particularly when used in vivo. As nonviral vectors, polycations may work well for efficient cell uptake and endosomal escape, because they do form compact and smaller complexes with plasmid DNA and carry amine groups, which give positive charge and buffering ability that allows safe escape from endosome/lysosome. However, this is a disadvantage in the following step, which is releasing the plasmid DNA within the cytosol. In order to initiate transcription and enhance gene expression, the polymer/plasmid complex should dissociate after releasing from endosome safely and effectively. There are also other limitations with some of the polycationic carriers, for example, aggregation, toxicity, etc. Intelligent polymers, also called as 'stimuli responsive polymers', have a great potential as nonviral vectors to obtain site-, timing-, and duration period-specific gene expression, which is already exhibited in recent studies that are briefly summarized here. Gene Therapy (2005) 12, S139-S145.

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Section: Intelligent Polymeric Vectors In Gene Therapymentioning

confidence: 99%

Intelligent polymers as nonviral vectors

2005

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“…During cell division, the nuclear membrane is temporarily disassembled, leading to the 'mitotic window of opportunity' in which the probability of pDNA to reach the nuclear interior of the newly formed daughter cells apparently increases significantly [7,8]. In a recent review, we proposed several strategies to enhance pDNA delivery during mitosis [9].…”

Section: Introductionmentioning

confidence: 99%

Cell division responsive peptides for optimized plasmid DNA delivery: The mitotic window of opportunity?

Remaut

Symens

Lucas

et al. 2014

Journal of Controlled Release

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The delivery of plasmid DNA remains hard to achieve, especially due to the presence of the nuclear membrane barrier. During cell division, however, the nuclear membrane is temporarily disassembled. We evaluated two different strategies to optimize plasmid DNA delivery in dividing cells: 1) phosphorylation responsive peptides that release plasmid DNA preferentially during mitosis and 2) chromatin targeting peptides to anchor plasmid DNA in newly formed nuclei upon cell division. Peptide/DNA particles alone were not efficient in penetrating cells. Upon co-delivery with lipid-based carriers, however, transfection efficiency drastically improved when compared to controls. For the phosphorylation responsive peptides, the presence of the phosphorylation sequence slightly increased transfection efficiency. For the chromatin targeting peptides, however, the chromatin targeting sequence did not seem to be the main reason for the improvement of transfection efficiency when applied in living cells. In conclusion, the pre-condensation of plasmid DNA with peptides improves lipid based delivery, but the nature of the peptides (cell responsive or not) does not seem to be the main reason for the improvement. It seems that the nuclear entry of foreign plasmid DNA is still under tight control, even during the mitotic window of opportunity.

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“…As most target tissues are nondividing in vivo, the nuclear membrane is a major obstacle to gene transfer and must be circumvented to improve expression from nonviral vectors. [3][4][5][6][7][8] Our laboratory has begun to design plasmid vectors that achieve efficient gene expression by targeting constructs to the nuclear compartment of specific cell types. [9][10][11][12][13] Initially, we demonstrated that inclusion of as little as 72 bp of the simian virus 40 (SV40) promoter/ enhancer in plasmid vectors facilitates nuclear import in all cell types tested.…”

Section: Introductionmentioning

confidence: 99%

Cell-specific nuclear import of plasmid DNA in smooth muscle requires tissue-specific transcription factors and DNA sequences

Miller

Dean

2008

Gene Ther

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Two shortcomings of nonviral gene therapy are a lack of tissue-specific targeting of vectors and low levels of gene transfer. Our laboratory has begun to address these limitations by designing plasmids that enter the nucleus of specific cell types in the absence of cell division, thereby enhancing expression in a controlled manner. We have shown that a 176 bp portion of the smooth muscle g-actin (SMGA) promoter can mediate plasmid nuclear import specifically in smooth muscle cells (SMCs). Here, we demonstrate that the binding sites for serum response factor (SRF) and NKX3-1/3-2 within this DNA nuclear targeting sequence (DTS) are required for plasmid nuclear import. Knockdown of these factors with siRNA abrogates plasmid nuclear import, indicating that they are necessary cofactors. In addition, coinjection of recombinant SRF and Nkx3.2 with the vector in TC7 epithelial cells rescues import. Finally, we show that the SRF nuclear localization sequence (NLS) is required for vector nuclear import. We propose that SRF and NKX3-1/3-2 bind the SMGA DTS in the cytoplasm, thus coating the plasmid with NLSs that mediate translocation across the nuclear pore complex. This discovery could aid in the development of more efficient nonviral vectors for gene transfer to SMCs.

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Cell cycle dependence of gene transfer by lipoplex, polyplex and recombinant adenovirus

Cited by 481 publications

References 30 publications

Intelligent polymers as nonviral vectors

Intelligent polymers as nonviral vectors

Cell division responsive peptides for optimized plasmid DNA delivery: The mitotic window of opportunity?

Cell-specific nuclear import of plasmid DNA in smooth muscle requires tissue-specific transcription factors and DNA sequences

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