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ARN
Architecture et réactivité de l'ARN
Publications
2011
Al-Jamal Khuloud T, Gherardini Lisa, Bardi Giuseppe, Nunes Antonio, Guo Chang, Bussy Cyrill, Herrero Antonia M, Bianco Alberto, Prato Maurizio, Kostarelos Kostas, Pizzorusso Tommaso
Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing Article de journal
Dans: Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 27, p. 10952–10957, 2011, ISSN: 1091-6490.
Résumé | Liens | BibTeX | Étiquettes: Animals, Apoptosis, Base Sequence, Brain Ischemia, carbon, Caspase 3, Caspase Inhibitors, Cell Line, Cells, Cultured, Electron, Endothelin-1, Female, Genetic Therapy, I2CT, Inbred C57BL, Mice, Microscopy, Nanomedicine, Nanotubes, Neurons, Psychomotor Performance, Rats, RNA, RNA Interference, Small Interfering, Sprague-Dawley, Team-Bianco, Transmission
@article{al-jamal_functional_2011,
title = {Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing},
author = {Khuloud T Al-Jamal and Lisa Gherardini and Giuseppe Bardi and Antonio Nunes and Chang Guo and Cyrill Bussy and Antonia M Herrero and Alberto Bianco and Maurizio Prato and Kostas Kostarelos and Tommaso Pizzorusso},
doi = {10.1073/pnas.1100930108},
issn = {1091-6490},
year = {2011},
date = {2011-07-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {108},
number = {27},
pages = {10952--10957},
abstract = {Stroke is the second cause of death worldwide with ischemic stroke accounting for 80% of all stroke insults. Caspase-3 activation contributes to brain tissue loss and downstream biochemical events that lead to programmed cell death after traumatic brain injury. Alleviation of symptoms following ischemic neuronal injury can be potentially achieved by either genetic disruption or pharmacological inhibition of caspases. Here, we studied whether silencing of Caspase-3 using carbon nanotube-mediated in vivo RNA interference (RNAi) could offer a therapeutic opportunity against stroke. Effective delivery of siRNA directly to the CNS has been shown to normalize phenotypes in animal models of several neurological diseases. It is shown here that peri-lesional stereotactic administration of a Caspase-3 siRNA (siCas 3) delivered by functionalized carbon nanotubes (f-CNT) reduced neurodegeneration and promoted functional preservation before and after focal ischemic damage of the rodent motor cortex using an endothelin-1 induced stroke model. These observations illustrate the opportunity offered by carbon nanotube-mediated siRNA delivery and gene silencing of neuronal tissue applicable to a variety of different neuropathological conditions where intervention at well localized brain foci may offer therapeutic and functional benefits.},
keywords = {Animals, Apoptosis, Base Sequence, Brain Ischemia, carbon, Caspase 3, Caspase Inhibitors, Cell Line, Cells, Cultured, Electron, Endothelin-1, Female, Genetic Therapy, I2CT, Inbred C57BL, Mice, Microscopy, Nanomedicine, Nanotubes, Neurons, Psychomotor Performance, Rats, RNA, RNA Interference, Small Interfering, Sprague-Dawley, Team-Bianco, Transmission},
pubstate = {published},
tppubtype = {article}
}
Stroke is the second cause of death worldwide with ischemic stroke accounting for 80% of all stroke insults. Caspase-3 activation contributes to brain tissue loss and downstream biochemical events that lead to programmed cell death after traumatic brain injury. Alleviation of symptoms following ischemic neuronal injury can be potentially achieved by either genetic disruption or pharmacological inhibition of caspases. Here, we studied whether silencing of Caspase-3 using carbon nanotube-mediated in vivo RNA interference (RNAi) could offer a therapeutic opportunity against stroke. Effective delivery of siRNA directly to the CNS has been shown to normalize phenotypes in animal models of several neurological diseases. It is shown here that peri-lesional stereotactic administration of a Caspase-3 siRNA (siCas 3) delivered by functionalized carbon nanotubes (f-CNT) reduced neurodegeneration and promoted functional preservation before and after focal ischemic damage of the rodent motor cortex using an endothelin-1 induced stroke model. These observations illustrate the opportunity offered by carbon nanotube-mediated siRNA delivery and gene silencing of neuronal tissue applicable to a variety of different neuropathological conditions where intervention at well localized brain foci may offer therapeutic and functional benefits.
2009
Monneaux Fanny, Muller Sylviane
Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects Article de journal
Dans: Arthritis Research & Therapy, vol. 11, no. 3, p. 234, 2009, ISSN: 1478-6362.
Résumé | Liens | BibTeX | Étiquettes: Animals, Clinical Trials as Topic, Forecasting, Genetic Therapy, Humans, I2CT, Lupus Erythematosus, Monneaux, Systemic, Team-Dumortier
@article{monneaux_molecular_2009,
title = {Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects},
author = {Fanny Monneaux and Sylviane Muller},
doi = {10.1186/ar2711},
issn = {1478-6362},
year = {2009},
date = {2009-01-01},
journal = {Arthritis Research & Therapy},
volume = {11},
number = {3},
pages = {234},
abstract = {The prognosis of patients with systemic lupus erythematosus has greatly improved since treatment regimens combining corticosteroids and immunosuppressive medications have been widely adopted in therapeutic strategies given to these patients. Immune suppression is evidently efficient but also leads to higher susceptibility to infectious and malignant diseases. Toxic effects and sometimes unexpectedly dramatic complications of current therapies have been progressively reported. Identifying novel molecular targets therefore remains an important issue in the treatment of lupus. The aim of this review article is to highlight emerging pharmacological options and new therapeutic avenues for lupus with a particular focus on non-antibody molecular strategies.},
keywords = {Animals, Clinical Trials as Topic, Forecasting, Genetic Therapy, Humans, I2CT, Lupus Erythematosus, Monneaux, Systemic, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
The prognosis of patients with systemic lupus erythematosus has greatly improved since treatment regimens combining corticosteroids and immunosuppressive medications have been widely adopted in therapeutic strategies given to these patients. Immune suppression is evidently efficient but also leads to higher susceptibility to infectious and malignant diseases. Toxic effects and sometimes unexpectedly dramatic complications of current therapies have been progressively reported. Identifying novel molecular targets therefore remains an important issue in the treatment of lupus. The aim of this review article is to highlight emerging pharmacological options and new therapeutic avenues for lupus with a particular focus on non-antibody molecular strategies.
2008
Prato Maurizio, Kostarelos Kostas, Bianco Alberto
Functionalized carbon nanotubes in drug design and discovery Article de journal
Dans: Accounts of Chemical Research, vol. 41, no. 1, p. 60–68, 2008, ISSN: 1520-4898.
Résumé | Liens | BibTeX | Étiquettes: Animals, carbon, Communicable Diseases, Drug Carriers, Drug Design, Genetic Therapy, Humans, I2CT, Immunization, Nanotubes, Neoplasms, Team-Bianco
@article{prato_functionalized_2008,
title = {Functionalized carbon nanotubes in drug design and discovery},
author = {Maurizio Prato and Kostas Kostarelos and Alberto Bianco},
doi = {10.1021/ar700089b},
issn = {1520-4898},
year = {2008},
date = {2008-01-01},
journal = {Accounts of Chemical Research},
volume = {41},
number = {1},
pages = {60--68},
abstract = {Carbon nanotubes (CNTs) have been proposed and actively explored as multipurpose innovative carriers for drug delivery and diagnostic applications. Their versatile physicochemical features enable the covalent and noncovalent introduction of several pharmaceutically relevant entities and allow for rational design of novel candidate nanoscale constructs for drug development. CNTs can be functionalized with different functional groups to carry simultaneously several moieties for targeting, imaging, and therapy. Among the most interesting examples of such multimodal CNT constructs described in this Account is one carrying a fluorescein probe together with the antifungal drug amphotericin B or fluorescein and the antitumor agent methotrexate. The biological action of the drug in these cases is retained or, as in the case of amphotericin B constructs, enhanced, while CNTs are able to reduce the unwanted toxicity of the drug administered alone. Ammonium-functionalized CNTs can also be considered very promising vectors for gene-encoding nucleic acids. Indeed, we have formed stable complexes between cationic CNTs and plasmid DNA and demonstrated the enhancement of the gene therapeutic capacity in comparison to DNA alone. On the other hand, CNTs conjugated with antigenic peptides can be developed as a new and effective system for synthetic vaccine applications. What makes CNTs quite unique is their ability, first shown by our groups in 2004, to passively cross membranes of many different types of cells following a translocation mechanism that has been termed the nanoneedle mechanism. In that way, CNTs open innumerable possibilities for future drug discovery based on intracellular targets that have been hard to reach until today. Moreover, adequately functionalized CNTs as those shown in this Account can be rapidly eliminated from the body following systemic administration offering further encouragment for their development. CNT excretion rates and accumulation in organs and any reactivity with the immune system will determine the CNT safety profile and, consequently, any further pharmaceutical development. Caution is advised about the need for systematic data on the long-term fate of these very interesting and versatile nano-objects in correlation with the type of CNT material used. CNTs are gradually plyaing a bigger and more important role in the emerging field of nanomedicine; however, we need to guarantee that the great opportunities they offer will be translated into feasible and safe constructs to be included in drug discovery and development pipelines.},
keywords = {Animals, carbon, Communicable Diseases, Drug Carriers, Drug Design, Genetic Therapy, Humans, I2CT, Immunization, Nanotubes, Neoplasms, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
Carbon nanotubes (CNTs) have been proposed and actively explored as multipurpose innovative carriers for drug delivery and diagnostic applications. Their versatile physicochemical features enable the covalent and noncovalent introduction of several pharmaceutically relevant entities and allow for rational design of novel candidate nanoscale constructs for drug development. CNTs can be functionalized with different functional groups to carry simultaneously several moieties for targeting, imaging, and therapy. Among the most interesting examples of such multimodal CNT constructs described in this Account is one carrying a fluorescein probe together with the antifungal drug amphotericin B or fluorescein and the antitumor agent methotrexate. The biological action of the drug in these cases is retained or, as in the case of amphotericin B constructs, enhanced, while CNTs are able to reduce the unwanted toxicity of the drug administered alone. Ammonium-functionalized CNTs can also be considered very promising vectors for gene-encoding nucleic acids. Indeed, we have formed stable complexes between cationic CNTs and plasmid DNA and demonstrated the enhancement of the gene therapeutic capacity in comparison to DNA alone. On the other hand, CNTs conjugated with antigenic peptides can be developed as a new and effective system for synthetic vaccine applications. What makes CNTs quite unique is their ability, first shown by our groups in 2004, to passively cross membranes of many different types of cells following a translocation mechanism that has been termed the nanoneedle mechanism. In that way, CNTs open innumerable possibilities for future drug discovery based on intracellular targets that have been hard to reach until today. Moreover, adequately functionalized CNTs as those shown in this Account can be rapidly eliminated from the body following systemic administration offering further encouragment for their development. CNT excretion rates and accumulation in organs and any reactivity with the immune system will determine the CNT safety profile and, consequently, any further pharmaceutical development. Caution is advised about the need for systematic data on the long-term fate of these very interesting and versatile nano-objects in correlation with the type of CNT material used. CNTs are gradually plyaing a bigger and more important role in the emerging field of nanomedicine; however, we need to guarantee that the great opportunities they offer will be translated into feasible and safe constructs to be included in drug discovery and development pipelines.