Novel Branching Membrane Translocational Peptide as Gene Delivery Vector

Tung, Ching–Hsuan; Mueller, Stephanie; Weissleder, Ralph

doi:10.1016/s0968-0896(02)00248-1

Cited by 81 publications

(61 citation statements)

References 47 publications

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“…Previous reports have also shown that small complexes of polyarginine-DNA (1-2 lm) exhibit reduced transfection efficiency in a rat fibroblast cell line than complexes of larger size (10 lm) [42]. Ogris et al [43] reported that larger particles (0.03-0.06 lm) of DNA ⁄ transferrin-PEI complexes showed 100-to 500-fold higher luciferase gene expression in Neuro2A neuroblastoma cells and erythromyeloid K562 cells than smaller complex particles (30-60 nm). These studies indicate that complex size may play an important role in determining the transfection efficiency of a polycationic peptide.…”

Section: Discussionmentioning

confidence: 93%

Study of uptake of cell penetrating peptides and their cargoes in permeabilized wheat immature embryos

Chugh¹,

Eudes²

2008

The FEBS Journal

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Cell-penetrating peptides (CPPs) comprise a fast growing class of short length peptides that differ in sequence, size and charge but share a common characteristic ability to translocate across the plasma membrane. It has been demonstrated that CPPs can act efficiently as nonviral delivery vehicles for macromolecules that are much larger in size than their own and lack the self-potential to enter living cells due to the The uptake of five fluorescein labeled cell-penetrating peptides (Tat, Tat 2 , mutated-Tat, peptide vascular endothelial-cadherin and transportan) was studied in wheat immature embryos. Interestingly, permeabilization treatment of the embryos with toluene ⁄ ethanol (1 : 20, v ⁄ v with permeabilization buffer) resulted in a remarkably higher uptake of cell-penetrating peptides, whereas nonpermeabilized embryos failed to show significant cellpenetrating peptide uptake, as observed under fluorescence microscope and by fluorimetric analysis. Among the cell-penetrating peptides investigated, Tat monomer (Tat) showed highest fluorescence uptake (4.2-fold greater) in permeabilized embryos than the nonpermeabilized embryos. On the other hand, mutated-Tat serving as negative control did not show comparable fluorescence levels even in permeabilized embryos. A glucuronidase histochemical assay revealed that Tat peptides can efficiently deliver functionally active b-glucuronidase (GUS) enzyme in permeabilized immature embryos. Tat 2 -mediated GUS enzyme delivery showed the highest number of embryos with GUS uptake (92.2%) upon permeabilization treatment with toluene ⁄ ethanol (1 : 40, v ⁄ v with permeabilization buffer) whereas only 51.8% of nonpermeabilized embryos showed Tat 2 -mediated GUS uptake. Low temperature, endocytosis and macropinocytosis inhibitors reduced delivery of the Tat 2 -GUS enzyme cargo complex. The results suggest that more than one mechanism of cell entry is involved simultaneously in cell-penetrating peptide-cargo uptake in wheat immature embryos. We also studied Tat 2 -plasmid DNA (carrying Act-1GUS) complex formation by gel retardation assay, DNaseI protection assay and confocal laser microscopy. Permeabilized embryos transfected with Tat 2 -plasmid DNA complex showed 3.3-fold higher transient GUS gene expression than the nonpermeabilized embryos. Furthermore, addition of cationic transfecting agent LipofectamineÔ 2000 to the Tat 2 -plasmid DNA complex resulted in 1.5-fold higher transient GUS gene expression in the embryos. This is the first report demonstrating translocation of various cell-penetrating peptides and their potential to deliver macromolecules in wheat immature embryos in the presence of a cell membrane permeabilizing agent.Abbreviations AID, arginine-rich intracellular delivery; CPP, cell-penetrating peptide; EIPA, 5-(N-ethyl N-isopropyl) amirolide; b-GUS, b-glucuronidase; M-Tat, mutated-Tat; pVEC, peptide vascular endothelial-cadherin.

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Section: Discussionmentioning

confidence: 93%

Study of uptake of cell penetrating peptides and their cargoes in permeabilized wheat immature embryos

Chugh¹,

Eudes²

2008

The FEBS Journal

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“…in order to overcome the problems with cell internalization (membrane interaction and cell penetration). For instance, the modification of a polylysine dendritic scaffold with HIV tat protein sequences, which are described to be able to facilitate cellular and nuclear transport [148]; the modified polylysine dendrimers containing lipidated units developed by Bayele et al [149], which were able to efficiently deliver oligonucleotides into the nucleus; and the cell penetrating peptide bearing polylysine dendrimers developed by Toth and Minchin's group [150,151]. On the other hand, Mixson et al studied the effect of the histidine loading of different His/Lys-based dendrimers [152][153][154].…”

Section: Dendrimersmentioning

confidence: 99%

Peptide-Based Polymer Therapeutics

2014

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Abstract:Polypeptides are envisaged to achieve a major impact on a number of different relevant areas such as biomedicine and biotechnology. Acquired knowledge and the increasing interest on amino acids, peptides and proteins is establishing a large panel of these biopolymers whose physical, chemical and biological properties are ruled by their controlled sequences and composition. Polymer therapeutics has helped to establish these polypeptide-based constructs as polymeric nanomedicines for different applications, such as disease treatment and diagnostics. Herein, we provide an overview of the advantages of these systems and the main methodologies for their synthesis, highlighting the different polypeptide architectures and the current research towards clinical applications.

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“…Moreover, arborizing Tat PTD was reported to further improve DNA transfection. 17 Furthermore, dual conjugation of Tat-p53 therapeutic protein with the ligand of CXCR4, which is a highly expressed chemokine receptor on tumor cells, resulted in strong specificity for PTD-mediated internalization. 11 This result implies therapeutic potential for PTD-mediated target cell-specific delivery.…”

Section: Introductionmentioning

confidence: 99%

Enhanced delivery efficiency of recombinant adenovirus into tumor and mesenchymal stem cells by a novel PTD

Youn

Park

et al. 2008

Cancer Gene Ther

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Protein transduction domains (PTDs) are small peptides that facilitate the transduction of large molecules such as polyproteins, DNA and viruses into a eukaryotic cell. Here, we demonstrated that a novel PTD (HP4) derived from herring protamine appeared to enter C6Bu1 rat glioma cell lines more rapidly than other known PTDs such as Tat, Antp and Hph-1. Moreover, HP4 significantly enhanced in vitro transduction of recombinant adenoviruses (rAds) into various cancer cell lines, mesenchymal stem cells (MSCs) and dendritic cells, which are relatively resistant to rAd infection. Enhancement of rAd delivery into C6Bu1 and MSCs by HP4 is 20 and 7 times higher than that by Tat, respectively. The increase in the expression of rAd encoding IL-12N220L by HP4 is proportional to its antitumor effect in the ex vivo transduced mouse colon cancer model. Thus, these results suggest that HP4 could be utilized to improve the transduction efficiency of rAd, resulting in enhanced efficacy of rAd-mediated gene therapy, especially for ex vivotransduced cell therapy.

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Novel Branching Membrane Translocational Peptide as Gene Delivery Vector

Cited by 81 publications

References 47 publications

Study of uptake of cell penetrating peptides and their cargoes in permeabilized wheat immature embryos

Study of uptake of cell penetrating peptides and their cargoes in permeabilized wheat immature embryos

Peptide-Based Polymer Therapeutics

Enhanced delivery efficiency of recombinant adenovirus into tumor and mesenchymal stem cells by a novel PTD

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