Publications
2021
Dahlet Thomas, Truss Matthias, Frede Ute, Adhami Hala Al, Bardet Anaïs F., Dumas Michael, Vallet Judith, Chicher Johana, Hammann Philippe, Kottnik Sarah, Hansen Peter, Luz Uschi, Alvarez Gonzalo, Auclair Ghislain, Hecht Jochen, Robinson Peter N., Hagemeier Christian, Weber Michael
E2F6 initiates stable epigenetic silencing of germline genes during embryonic development Article de journal
Dans: Nature Communications, vol. 12, no. 1, p. 3582, 2021, ISSN: 2041-1723.
Résumé | Liens | BibTeX | Étiquettes: Animals, Binding Sites, Cell Differentiation, CpG Islands, CRISPR-Cas Systems, DNA Methylation, E2F6 Transcription Factor, Embryonic Development, Epigenesis, Gene Silencing, Genetic, Germ Cells, Knockout, Mice, Mouse Embryonic Stem Cells, Polycomb Repressive Complex 1, PPSE, RNA, Small Interfering
@article{dahlet_e2f6_2021,
title = {E2F6 initiates stable epigenetic silencing of germline genes during embryonic development},
author = {Thomas Dahlet and Matthias Truss and Ute Frede and Hala Al Adhami and Anaïs F. Bardet and Michael Dumas and Judith Vallet and Johana Chicher and Philippe Hammann and Sarah Kottnik and Peter Hansen and Uschi Luz and Gonzalo Alvarez and Ghislain Auclair and Jochen Hecht and Peter N. Robinson and Christian Hagemeier and Michael Weber},
doi = {10.1038/s41467-021-23596-w},
issn = {2041-1723},
year = {2021},
date = {2021-06-01},
journal = {Nature Communications},
volume = {12},
number = {1},
pages = {3582},
abstract = {In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes; however, the molecular mechanisms of this specificity remain unclear. Here, we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in embryos, a function that critically depends on the E2F6 marked box domain. Inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Furthermore, E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long-term epigenetic silencing during mouse development.},
keywords = {Animals, Binding Sites, Cell Differentiation, CpG Islands, CRISPR-Cas Systems, DNA Methylation, E2F6 Transcription Factor, Embryonic Development, Epigenesis, Gene Silencing, Genetic, Germ Cells, Knockout, Mice, Mouse Embryonic Stem Cells, Polycomb Repressive Complex 1, PPSE, RNA, Small Interfering},
pubstate = {published},
tppubtype = {article}
}
2010
Al-Jamal Khuloud T, Toma Francesca M, Yilmazer Açelya, Ali-Boucetta Hanene, Nunes Antonio, Herrero Maria-Antonia, Tian Bowen, Eddaoudi Ayad, Eddaoui Ayad, Al-Jamal Wafa' T, Bianco Alberto, Prato Maurizio, Kostarelo Kostas
Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes Article de journal
Dans: FASEB journal: official publication of the Federation of American Societies for Experimental Biology, vol. 24, no. 11, p. 4354–4365, 2010, ISSN: 1530-6860.
Résumé | Liens | BibTeX | Étiquettes: Biological Transport, carbon, Cations, Cell Line, Cell Survival, Gene Silencing, HeLa Cells, Humans, I2CT, Models, Molecular, Nanotubes, RNA, Small Interfering, Team-Bianco, Transfection, tumor
@article{al-jamal_enhanced_2010,
title = {Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes},
author = {Khuloud T Al-Jamal and Francesca M Toma and Açelya Yilmazer and Hanene Ali-Boucetta and Antonio Nunes and Maria-Antonia Herrero and Bowen Tian and Ayad Eddaoudi and Ayad Eddaoui and Wafa' T Al-Jamal and Alberto Bianco and Maurizio Prato and Kostas Kostarelo},
doi = {10.1096/fj.09-141036},
issn = {1530-6860},
year = {2010},
date = {2010-11-01},
journal = {FASEB journal: official publication of the Federation of American Societies for Experimental Biology},
volume = {24},
number = {11},
pages = {4354--4365},
abstract = {One of the major obstacles to the clinical development of gene silencing by small interfering RNA (siRNA) is its effective cytoplasmic delivery. Carbon nanotubes have been proposed as novel nanomaterials that can offer significant advantages for the intracellular delivery of nucleic acids, such as siRNA. We recently demonstrated in a proof-of-principle study that amino-functionalized multiwalled carbon nanotubes (f-MWNT) can effectively deliver in vivo an siRNA sequence, triggering cell apoptosis that results in human lung xenograft eradication and prolonged survival. In the present study, we demonstrate how a newly synthesized series of polycationic dendron-MWNT constructs with a precisely tailored number of amino functions (dendron generations) can complex and effectively deliver double-stranded siRNA to achieve gene silencing in vitro. A systematic comparison between the f-MWNT series in terms of cellular uptake, cytotoxicity, and siRNA complexation is offered. Significant improvement in siRNA delivery with the dendron-MWNT conjugates is shown, and gene silencing was obtained in 2 human cell lines using 2 different siRNA sequences. The study reveals that through f-MWNT structure-biological function analysis novel nanotube-based siRNA transfer vectors can be designed with minimal cytotoxicity and effective delivery and gene-silencing capabilities.},
keywords = {Biological Transport, carbon, Cations, Cell Line, Cell Survival, Gene Silencing, HeLa Cells, Humans, I2CT, Models, Molecular, Nanotubes, RNA, Small Interfering, Team-Bianco, Transfection, tumor},
pubstate = {published},
tppubtype = {article}
}
2009
Herrero Antonia M, Toma Francesca M, Al-Jamal Khuloud T, Kostarelos Kostas, Bianco Alberto, Ros Tatiana Da, Bano Fouzia, Casalis Loredana, Scoles Giacinto, Prato Maurizio
Synthesis and characterization of a carbon nanotube-dendron series for efficient siRNA delivery Article de journal
Dans: Journal of the American Chemical Society, vol. 131, no. 28, p. 9843–9848, 2009, ISSN: 1520-5126.
Résumé | Liens | BibTeX | Étiquettes: Acrylates, Animals, Azo Compounds, Biological Transport, carbon, Cytoplasm, Dendrimers, Drug Carriers, Ethylenediamines, Gene Silencing, HeLa Cells, Humans, I2CT, Nanotubes, Polyamines, RNA, Small Interfering, Solubility, Team-Bianco, Thiosemicarbazones, Transfection, water
@article{herrero_synthesis_2009,
title = {Synthesis and characterization of a carbon nanotube-dendron series for efficient siRNA delivery},
author = {Antonia M Herrero and Francesca M Toma and Khuloud T Al-Jamal and Kostas Kostarelos and Alberto Bianco and Tatiana Da Ros and Fouzia Bano and Loredana Casalis and Giacinto Scoles and Maurizio Prato},
doi = {10.1021/ja903316z},
issn = {1520-5126},
year = {2009},
date = {2009-07-01},
journal = {Journal of the American Chemical Society},
volume = {131},
number = {28},
pages = {9843--9848},
abstract = {A new series of dendron-functionalized multiwalled carbon nanotube (MWNT) derivatives, characterized by the presence of numerous positively charged tetraalkyl ammonium salts at the periphery of the dendron, has been synthesized. The positive charges on the MWNT surface, coupled with the unique ability of carbon nanotubes (CNTs) to penetrate cell membranes, make the new derivatives potentially ideal vectors for siRNA delivery. Using a fluorescently labeled, noncoding siRNA sequence, we demonstrate that cytoplasmic delivery of the nucleic acid is remarkably increased throughout the different dendron generations. The work reported here highlights the fact that dendron-functionalized CNTs can be rationally designed as efficient carriers of siRNA that can eventually lead to gene silencing.},
keywords = {Acrylates, Animals, Azo Compounds, Biological Transport, carbon, Cytoplasm, Dendrimers, Drug Carriers, Ethylenediamines, Gene Silencing, HeLa Cells, Humans, I2CT, Nanotubes, Polyamines, RNA, Small Interfering, Solubility, Team-Bianco, Thiosemicarbazones, Transfection, water},
pubstate = {published},
tppubtype = {article}
}
Podesta Jennifer E, Al-Jamal Khuloud T, Herrero Antonia M, Tian Bowen, Ali-Boucetta Hanene, Hegde Vikas, Bianco Alberto, Prato Maurizio, Kostarelos Kostas
Antitumor activity and prolonged survival by carbon-nanotube-mediated therapeutic siRNA silencing in a human lung xenograft model Article de journal
Dans: Small (Weinheim an Der Bergstrasse, Germany), vol. 5, no. 10, p. 1176–1185, 2009, ISSN: 1613-6829.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antineoplastic Agents, Apoptosis, carbon, Cell Line, Cell Proliferation, Electrophoresis, Gene Silencing, Humans, I2CT, Liposomes, Lung Neoplasms, Mice, Nanomedicine, Nanotubes, RNA, Small Interfering, Survival Analysis, Team-Bianco, tumor, Xenograft Model Antitumor Assays
@article{podesta_antitumor_2009,
title = {Antitumor activity and prolonged survival by carbon-nanotube-mediated therapeutic siRNA silencing in a human lung xenograft model},
author = {Jennifer E Podesta and Khuloud T Al-Jamal and Antonia M Herrero and Bowen Tian and Hanene Ali-Boucetta and Vikas Hegde and Alberto Bianco and Maurizio Prato and Kostas Kostarelos},
doi = {10.1002/smll.200801572},
issn = {1613-6829},
year = {2009},
date = {2009-05-01},
journal = {Small (Weinheim an Der Bergstrasse, Germany)},
volume = {5},
number = {10},
pages = {1176--1185},
abstract = {Carbon nanotubes are novel nanomaterials that are thought to offer potential benefits to a variety of biomedical and clinical applications. In this study, the treatment of a human lung carcinoma model in vivo using siRNA sequences leading to cytotoxicity and cell death is carried out using either cationic liposomes (DOTAP:cholesterol) or amino-functionalized multi-walled carbon nanotubes (MWNT - NH(+)(3)). Validation for the most cytotoxic siRNA sequence using a panel of human carcinoma and murine cells reveals that the proprietary siTOX sequence is human specific and can lead to significant cytotoxic activities delivered both by liposome or MWNT - NH(+)(3) in vitro. A comparative study using both types of vector indicates that only MWNT - NH(+)(3):siRNA complexes administered intratumorally can elicit delayed tumor growth and increased survival of xenograft-bearing animals. siTOX delivery via the cationic MWNT - NH(+)(3) is biologically active in vivo by triggering an apoptotic cascade, leading to extensive necrosis of the human tumor mass. This suggests that carbon-nanotube-mediated delivery of siRNA by intratumoral administration leads to successful and statistically significant suppression of tumor volume, followed by a concomitant prolongation of survival of human lung tumor-bearing animals. The direct comparison between carbon nanotubes and liposomes demonstrates the potential advantages offered by carbon nanotubes for the intracellular delivery of therapeutic agents in vivo. The present work may act as the impetus for further studies to explore the therapeutic capacity of chemically functionalized carbon nanotubes to deliver siRNA directly into the cytoplasm of target cells and achieve effective therapeutic silencing in various disease indications where local delivery is feasible or desirable.},
keywords = {Animals, Antineoplastic Agents, Apoptosis, carbon, Cell Line, Cell Proliferation, Electrophoresis, Gene Silencing, Humans, I2CT, Liposomes, Lung Neoplasms, Mice, Nanomedicine, Nanotubes, RNA, Small Interfering, Survival Analysis, Team-Bianco, tumor, Xenograft Model Antitumor Assays},
pubstate = {published},
tppubtype = {article}
}
Berry Bassam, Deddouche Safia, Kirschner Doris, Imler Jean-Luc, Antoniewski Christophe
Viral suppressors of RNA silencing hinder exogenous and endogenous small RNA pathways in Drosophila Article de journal
Dans: PloS One, vol. 4, no. 6, p. e5866, 2009, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antiviral Agents, Crosses, Double-Stranded, Gene Silencing, Genetic, Genetically Modified, Heterozygote, imler, Invertebrate, M3i, Photoreceptor Cells, Reverse Transcriptase Polymerase Chain Reaction, RNA, RNA Interference, Transgenes
@article{berry_viral_2009,
title = {Viral suppressors of RNA silencing hinder exogenous and endogenous small RNA pathways in Drosophila},
author = {Bassam Berry and Safia Deddouche and Doris Kirschner and Jean-Luc Imler and Christophe Antoniewski},
doi = {10.1371/journal.pone.0005866},
issn = {1932-6203},
year = {2009},
date = {2009-01-01},
journal = {PloS One},
volume = {4},
number = {6},
pages = {e5866},
abstract = {BACKGROUND: In plants and insects, RNA interference (RNAi) is the main responder against viruses and shapes the basis of antiviral immunity. Viruses counter this defense by expressing viral suppressors of RNAi (VSRs). While VSRs in Drosophila melanogaster were shown to inhibit RNAi through different modes of action, whether they act on other silencing pathways remained unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that expression of various plant and insect VSRs in transgenic flies does not perturb the Drosophila microRNA (miRNA) pathway; but in contrast, inhibits antiviral RNAi and the RNA silencing response triggered by inverted repeat transcripts, and injection of dsRNA or siRNA. Strikingly, these VSRs also suppressed transposon silencing by endogenous siRNAs (endo-siRNAs). CONCLUSIONS/SIGNIFICANCE: Our findings identify VSRs as tools to unravel small RNA pathways in insects and suggest a cosuppression of antiviral RNAi and endo-siRNA silencing by viruses during fly infections.},
keywords = {Animals, Antiviral Agents, Crosses, Double-Stranded, Gene Silencing, Genetic, Genetically Modified, Heterozygote, imler, Invertebrate, M3i, Photoreceptor Cells, Reverse Transcriptase Polymerase Chain Reaction, RNA, RNA Interference, Transgenes},
pubstate = {published},
tppubtype = {article}
}