Transformed and immortalized cellular uptake of oligodeoxynucleoside phosphorothioates, 3′-Alkylamino oligodeoxynucleotides, 2′-o-methyl oligoribonucleotides, oligodeoxynucleoside methylphosphonates, and peptide nucleic acids

Gray, Gary D.; Basu, Soumitra; Wickstrom, Eric

doi:10.1016/s0006-2952(97)82440-9

Cited by 101 publications

(75 citation statements)

References 37 publications

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“…For example, extracellularly delivered fluorescent-labelled PNA remained within cytoplasmic endosomes, and did not localise within the nucleus. 7 By contrast, nuclear uptake was clearly demonstrated with the radiolabelled PNA molecules 24 and with both biotinylated PNA and biotinylated peptide-PNA in our study.…”

Section: Discussioncontrasting

confidence: 72%

“…Unlike the fluorochrome tagged PNAs used by Bonham and colleagues, 7 these investigators radiolabelled the PNA with 14 Cformaldehyde. 24 It is therefore possible that these different labelling techniques influence the rate and pattern of PNA uptake in these studies. For example, extracellularly delivered fluorescent-labelled PNA remained within cytoplasmic endosomes, and did not localise within the nucleus.…”

Section: Discussionmentioning

confidence: 99%

“…7 Despite a sensitive semi-quantitative detection method, relatively high concentrations of PNA (Ͼ1 m) were needed to demonstrate uptake in our study. PNA uptake has been shown to occur in transformed and immortalised cell lines, 24 probably by fluid-phase endocytosis. Unlike the fluorochrome tagged PNAs used by Bonham and colleagues, 7 these investigators radiolabelled the PNA with 14 Cformaldehyde.…”

Section: Discussionmentioning

confidence: 99%

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Peptide nucleic acid delivery to human mitochondria

et al. 1999

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Peptide nucleic acids (PNAs) are synthetic polynucleobase as therapeutic agents for mtDNA disease, we attempted to molecules, which bind to DNA and RNA with high affinity localise PNAs to the mitochondrial matrix. When attached and specificity. Although PNAs have enormous potential to the presequence peptide of the nuclear-encoded human as anti-sense agents, the success of PNA-mediated gene cytochrome c oxidase (COX) subunit VIII, the biotinylated therapy will require efficient cellular uptake and sub-cellular PNA was successfully imported into isolated organelles in trafficking. At present these mechanisms are poorly undervitro. Furthermore, delivery of the biotinylated peptide-PNA stood. To address this, we have studied the uptake of biotito mitochondria in intact cells was confirmed by confocal nylated PNAs into cultured cell lines using fluorescence microscopy. These studies demonstrate that biotinylated confocal microscopy. In human myoblasts, initial punctate PNAs can be directed across cell membranes and to a staining was followed by the release of PNAs into the cytospecific sub-cellular compartment within human cellssol and subsequent localisation and concentration in the highlighting the importance of these novel molecules for nucleus. To determine whether PNAs could also be used human gene therapy.

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Section: Discussioncontrasting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Peptide nucleic acid delivery to human mitochondria

et al. 1999

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“…PNAs are resistant to nucleases and proteases (40) and consequently are more stable in cells than oligonucleotides. Though potentially capable of blocking gene expression in a selective and specific manner (41), PNAs have never been shown to be effective antigene agents in intact live cells in culture because of their limited ability to reach cell nuclei (42). Our results from flow cytometry, Northern blots, and Western blots are demonstrating that PNA CXCR3 significantly and specifically inhibit CXCR3 mRNA and protein expression in the spleen T cells and skin grafts.…”

Section: Discussionmentioning

confidence: 87%

Peptide Nucleic Acid Antisense Prolongs Skin Allograft Survival by Means of Blockade of CXCR3 Expression Directing T Cells into Graft

Ming

Wang

Huang

et al. 2003

The Journal of Immunology

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CXCR3, predominantly expressed on memory/activated T cells, is a receptor for both IFN-γ-inducible protein 10/CXC chemokine ligand (CXCL)10 and monokine induced by IFN-γ/CXCL9. It was reported that CXC chemokines IFN-γ-inducible protein 10/CXCL10 and monokine induced by IFN-γ/CXCL9 play a critical role in the allograft rejection. We report that CXCR3 is a dominant factor directing T cells into mouse skin allograft, and that peptide nucleic acid (PNA) CXCR3 antisense significantly prolongs skin allograft survival by means of blockade of CXCR3 expression directing T cells into allografts in mice. We found that CXCR3 is highly up-regulated in spleen T cells and allografts from BALB/c recipients by day 7 of receiving transplantation, whereas CCR5 expression is moderately increased. We designed PNA CCR5 and PNA CXCR3 antisenses, and i.v. treated mice that received skin allograft transplantations. The PNA CXCR3 at a dosage of 10 mg/kg/day significantly prolonged mouse skin allograft survival (17.1 ± 2.4 days) compared with physiological saline treatment (7.5 ± 0.7 days), whereas PNA CCR5 (10 mg/kg/day) marginally prolonged skin allograft survival (10.7 ± 1.1 days). The mechanism of prolongation of skin allograft survival is that PNA CXCR3 directly blocks the CXCR3 expression in T cells, which is responsible for directing T cells into skin allograft to induce acute rejection, without interfering with other functions of the T cells. These results were obtained at mRNA and protein levels by flow cytometry and real-time quantitative RT-PCR technique, and confirmed by chemotaxis, Northern and Western blot assays, and histological evaluation of skin grafts. The present study indicates the therapeutic potential of PNA CXCR3 to prevent acute transplantation rejection.

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“…Although PNAs are internalized poorly by cells, 25 fluoresceinyl-PNA-Gly 4 -d(Cys-Ser-Lys-Cys) was internalized efficiently and specifically by cells overexpressing insulin-like growth factor 1 (IGF1) receptor, a characteristic marker of malignant cells. 26 d(Cys-Ser-Lys-Cys) is a d-peptide retro-inverso analog of IGF1; fluoresceinyl-PNA-Gly 4 -d(Cys-Ala-Als-Cys) was not taken up by those cells.…”

Section: Introductionmentioning

confidence: 99%