Systemic Delivery of siRNA Down Regulates Brain Prion Protein and Ameliorates Neuropathology in Prion Disorder
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{"title"=>"Systemic delivery of siRNA down regulates brain prion protein and ameliorates neuropathology in prion disorder", "type"=>"journal", "authors"=>[{"first_name"=>"Sylvain", "last_name"=>"Lehmann", "scopus_author_id"=>"7102616467"}, {"first_name"=>"Aroa", "last_name"=>"Relano-Gines", "scopus_author_id"=>"12793976600"}, {"first_name"=>"Sarah", "last_name"=>"Resina", "scopus_author_id"=>"14064166200"}, {"first_name"=>"Elsa", "last_name"=>"Brillaud", "scopus_author_id"=>"57199557258"}, {"first_name"=>"Danielle", "last_name"=>"Casanova", "scopus_author_id"=>"57197000169"}, {"first_name"=>"Charles", "last_name"=>"Vincent", "scopus_author_id"=>"56061448700"}, {"first_name"=>"Claire", "last_name"=>"Hamela", "scopus_author_id"=>"55842037900"}, {"first_name"=>"Sophie", "last_name"=>"Poupeau", "scopus_author_id"=>"56061449400"}, {"first_name"=>"Mathieu", "last_name"=>"Laffont", "scopus_author_id"=>"56061556400"}, {"first_name"=>"Audrey", "last_name"=>"Gabelle", "scopus_author_id"=>"23984716300"}, {"first_name"=>"Constance", "last_name"=>"Delaby", "scopus_author_id"=>"9736389100"}, {"first_name"=>"Maxime", "last_name"=>"Belondrade", "scopus_author_id"=>"24504276000"}, {"first_name"=>"Jacques Damien", "last_name"=>"Arnaud", "scopus_author_id"=>"57197511780"}, {"first_name"=>"Maria Teresa", "last_name"=>"Alvarez", "scopus_author_id"=>"56061750300"}, {"first_name"=>"Jean Claude", "last_name"=>"Maurel", "scopus_author_id"=>"56368875800"}, {"first_name"=>"Patrick", "last_name"=>"Maurel", "scopus_author_id"=>"56657257600"}, {"first_name"=>"Carole", "last_name"=>"Crozet", "scopus_author_id"=>"6603503149"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"24551164", "doi"=>"10.1371/journal.pone.0088797", "sgr"=>"84895802528", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84895802528", "issn"=>"19326203", "pui"=>"372557800"}, "id"=>"799f89c0-396b-34ef-8ac9-00d1c328dc33", "abstract"=>"One of the main challenges for neurodegenerative disorders that are principally incurable is the development of new therapeutic strategies, which raises important medical, scientific and societal issues. Creutzfeldt-Jakob diseases are rare neurodegenerative fatal disorders which today remain incurable. The objective of this study was to evaluate the efficacy of the down-regulation of the prion protein (PrP) expression using siRNA delivered by, a water-in-oil microemulsion, as a therapeutic candidate in a preclinical study. After 12 days rectal mucosa administration of Aonys/PrP-siRNA in mice, we observed a decrease of about 28% of the brain PrP(C) level. The effect of Aonys/PrP-siRNA was then evaluated on prion infected mice. Several mice presented a delay in the incubation and survival time compared to the control groups and a significant impact was observed on astrocyte reaction and neuronal survival in the PrP-siRNA treated groups. These results suggest that a new therapeutic scheme based an innovative delivery system of PrP-siRNA can be envisioned in prion disorders.", "link"=>"http://www.mendeley.com/research/systemic-delivery-sirna-down-regulates-brain-prion-protein-ameliorates-neuropathology-prion-disorder", "reader_count"=>23, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>2, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>2, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>3, "Physics and Astronomy"=>1, "Chemical Engineering"=>1, "Chemistry"=>1, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>1}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"France"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1388129"], "description"=>"<p>Cytokine results.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "RNA interference", "drug discovery", "biotechnology", "genetics", "gene expression", "Molecular cell biology", "Drugs and devices", "Drug research and development", "Pharmacodynamics", "Infectious diseases", "Prion diseases", "Veterinary diseases", "Zoonotic diseases"], "article_id"=>936396, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sylvain Lehmann", "Aroa Relaño-Ginès", "Sarah Resina", "Elsa Brillaud", "Danielle Casanova", "Charles Vincent", "Claire Hamela", "Sophie Poupeau", "Mathieu Laffont", "Audrey Gabelle", "Constance Delaby", "Maxime Belondrade", "Jacques-Damien Arnaud", "Maria-Teresa Alvarez", "Jean-Claude Maurel", "Patrick Maurel", "Carole Crozet"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088797.t002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytokine_results_/936396", "title"=>"Cytokine results.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-14 03:45:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1388126"], "description"=>"<p>Panels A,B. Quantitation of vacuolar lesions after Hematoxylin & Eosin staining (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088797#pone-0088797-g004\" target=\"_blank\">figure 4</a>) revealed that siRNA have a slight impact. Panels D,E. Quantitation of astrocyte based on the GFAP immunostaining (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088797#pone-0088797-g004\" target=\"_blank\">figure 4</a>) showed significant differences between the Aonys/PrP-siRNA treated group and the two control groups (vehicle and scrambled-siRNA). Panels G,H. Quantitation of neurons based on the neuronal marker NeuN (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088797#pone-0088797-g004\" target=\"_blank\">figure 4</a>) revealed statistical differences between mice treated with PrP-siRNA and vehicle. Panels C,F,I. Data of individual levels of vacuolisation, NeuN or GFAP counts as a function of survival time did not show any correlation.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "RNA interference", "drug discovery", "biotechnology", "genetics", "gene expression", "Molecular cell biology", "Drugs and devices", "Drug research and development", "Pharmacodynamics", "Infectious diseases", "Prion diseases", "Veterinary diseases", "Zoonotic diseases", "immunohistolochemical"], "article_id"=>936393, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sylvain Lehmann", "Aroa Relaño-Ginès", "Sarah Resina", "Elsa Brillaud", "Danielle Casanova", "Charles Vincent", "Claire Hamela", "Sophie Poupeau", "Mathieu Laffont", "Audrey Gabelle", "Constance Delaby", "Maxime Belondrade", "Jacques-Damien Arnaud", "Maria-Teresa Alvarez", "Jean-Claude Maurel", "Patrick Maurel", "Carole Crozet"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088797.g005", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histological_and_Immunohistolochemical_data_analysis_/936393", "title"=>"Histological and Immunohistolochemical data analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-14 03:45:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1388125"], "description"=>"<p>Panel A. PrP<sup>Sc</sup> immunostaining was observed in all the mice (arrow). Panel B. Vacuolar lesions revealed after Hematoxylin & Eosin staining were apparent in all conditions. Immunohistochemical detections of the GFAP astrocyte marker (Panel C) and the neuronal marker NeuN were also performed (Panel D).</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "RNA interference", "drug discovery", "biotechnology", "genetics", "gene expression", "Molecular cell biology", "Drugs and devices", "Drug research and development", "Pharmacodynamics", "Infectious diseases", "Prion diseases", "Veterinary diseases", "Zoonotic diseases", "immunohistolochemical"], "article_id"=>936392, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sylvain Lehmann", "Aroa Relaño-Ginès", "Sarah Resina", "Elsa Brillaud", "Danielle Casanova", "Charles Vincent", "Claire Hamela", "Sophie Poupeau", "Mathieu Laffont", "Audrey Gabelle", "Constance Delaby", "Maxime Belondrade", "Jacques-Damien Arnaud", "Maria-Teresa Alvarez", "Jean-Claude Maurel", "Patrick Maurel", "Carole Crozet"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088797.g004", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histological_and_Immunohistolochemical_illustration_/936392", "title"=>"Histological and Immunohistolochemical illustration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-14 03:45:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1388120"], "description"=>"<p>Panel A. Brain homogenates of mice treated for 12(see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088797#pone-0088797-t001\" target=\"_blank\">Table 1</a>) with two doses of PrP<sup>C</sup> siRNA (Aonys/siPrP 300 (L) and 600 µg/kg), the vehicle only and scrambled-siRNA, were analysed for PrP<sup>C</sup> accumulation by Western blot. The C+ lane corresponds to a brain homogenate of untreated mice. A decrease of PrP<sup>C</sup> was apparent in siPrP treated mice. However there was a relative variability in detection in relation with the low linearity of the western blot. Panel B. Samples in A were analysed using ELISA for quantitation of PrP<sup>C</sup>. Graphic results of normalized PrP<sup>C</sup> were presented as medians and interquartile ranges. Statistical analysis (Kruskal-Wallis test) was used to evaluate the significance of the difference between the groups. The siPrP group (600 µg/kg) presents a significant reduction of PrP<sup>C</sup> levels. Panels C and D. Additional experiments were carried out (10 mice/groups) in which mice were treated or not with Aonys/PrP<sup>C</sup> siRNA at 600 µg/kg. Panel C. PrP<sup>C</sup> ELISA. Panel D. RT-Q-PCR quantitation (light Cycler) of PrP and GAPDH in Graphic results were presented as medians and interquartile ranges. Statistical analysis (Kruskal-Wallis test) was used to evaluate the significance of the difference between the groups. The siPrP group presents a significant reduction of both PrP<sup>C</sup> protein and RNA levels.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "RNA interference", "drug discovery", "biotechnology", "genetics", "gene expression", "Molecular cell biology", "Drugs and devices", "Drug research and development", "Pharmacodynamics", "Infectious diseases", "Prion diseases", "Veterinary diseases", "Zoonotic diseases", "vivo"], "article_id"=>936387, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sylvain Lehmann", "Aroa Relaño-Ginès", "Sarah Resina", "Elsa Brillaud", "Danielle Casanova", "Charles Vincent", "Claire Hamela", "Sophie Poupeau", "Mathieu Laffont", "Audrey Gabelle", "Constance Delaby", "Maxime Belondrade", "Jacques-Damien Arnaud", "Maria-Teresa Alvarez", "Jean-Claude Maurel", "Patrick Maurel", "Carole Crozet"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088797.g001", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_PrP_C_expression_in_AONYS_siRNA_treated_mice_/936387", "title"=>"In vivo PrP<sup>C</sup> expression in AONYS/siRNA-treated mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-14 03:45:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1388128"], "description"=>"<p>Chronology of the in vivo phase.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "RNA interference", "drug discovery", "biotechnology", "genetics", "gene expression", "Molecular cell biology", "Drugs and devices", "Drug research and development", "Pharmacodynamics", "Infectious diseases", "Prion diseases", "Veterinary diseases", "Zoonotic diseases", "vivo"], "article_id"=>936395, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sylvain Lehmann", "Aroa Relaño-Ginès", "Sarah Resina", "Elsa Brillaud", "Danielle Casanova", "Charles Vincent", "Claire Hamela", "Sophie Poupeau", "Mathieu Laffont", "Audrey Gabelle", "Constance Delaby", "Maxime Belondrade", "Jacques-Damien Arnaud", "Maria-Teresa Alvarez", "Jean-Claude Maurel", "Patrick Maurel", "Carole Crozet"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088797.t001", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chronology_of_the_in_vivo_phase_/936395", "title"=>"Chronology of the in vivo phase.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-14 03:45:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1388127"], "description"=>"<p>Graphic representation plotted as medians and interquartile ranges of selected blood cytokine levels in the three mice groups (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088797#pone-0088797-t002\" target=\"_blank\">table 2</a> for full data). Note that outliners characterized by very high cytokine levels were present in the siRNA groups only.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "RNA interference", "drug discovery", "biotechnology", "genetics", "gene expression", "Molecular cell biology", "Drugs and devices", "Drug research and development", "Pharmacodynamics", "Infectious diseases", "Prion diseases", "Veterinary diseases", "Zoonotic diseases"], "article_id"=>936394, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sylvain Lehmann", "Aroa Relaño-Ginès", "Sarah Resina", "Elsa Brillaud", "Danielle Casanova", "Charles Vincent", "Claire Hamela", "Sophie Poupeau", "Mathieu Laffont", "Audrey Gabelle", "Constance Delaby", "Maxime Belondrade", "Jacques-Damien Arnaud", "Maria-Teresa Alvarez", "Jean-Claude Maurel", "Patrick Maurel", "Carole Crozet"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088797.g006", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytokines_analysis_/936394", "title"=>"Cytokines analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-14 03:45:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1388122"], "description"=>"<p>Western blot analysis of PrP<sup>Sc</sup> in mouse brain lysates (Panel A.). Only representative samples of the mouse population are presented here. The classical ME7 PrP<sup>Sc</sup> bands were present at various intensity levels. The Ctr+ lane corresponds to a brain homogenate of ME7 scrapie mice loaded as a standard in every blot. Quantitation of the signal (Panel B.) normalized in each blot with respect to the Ctr+ sample showed no significant difference between groups. (Panel C.) Individual PrP<sup>Sc</sup> levels and survival times.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "RNA interference", "drug discovery", "biotechnology", "genetics", "gene expression", "Molecular cell biology", "Drugs and devices", "Drug research and development", "Pharmacodynamics", "Infectious diseases", "Prion diseases", "Veterinary diseases", "Zoonotic diseases", "sirna"], "article_id"=>936389, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sylvain Lehmann", "Aroa Relaño-Ginès", "Sarah Resina", "Elsa Brillaud", "Danielle Casanova", "Charles Vincent", "Claire Hamela", "Sophie Poupeau", "Mathieu Laffont", "Audrey Gabelle", "Constance Delaby", "Maxime Belondrade", "Jacques-Damien Arnaud", "Maria-Teresa Alvarez", "Jean-Claude Maurel", "Patrick Maurel", "Carole Crozet"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088797.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_siRNA_on_brain_PrP_Sc_content_/936389", "title"=>"Impact of siRNA on brain PrP<sup>Sc</sup> content.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-14 03:45:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1388121"], "description"=>"<p>Panel A. The incubation time in scrapie infected mice based on the presence of at least three clinical signs (among: waddling gait, flattened back, rough coat, sticky eye discharge, weight loss, very jumpy, hunched, incontinence) was plotted as medians and interquartile ranges in the three groups: Aonys/PrP<sup>C</sup> siRNA (siPrP 600 µg/kg), Aonys vehicle only and Aonys/scrambled-siRNA. The survival times of the three groups of infected mice were plotted as medians and interquartile ranges (Panel B.) and Kaplan-Meier survival curves (Panel C.). No statistical difference was observed between each group neither for the incubation period nor the survival time.</p>", "links"=>[], "tags"=>["Biochemistry", "Nucleic acids", "rna", "RNA interference", "drug discovery", "biotechnology", "genetics", "gene expression", "Molecular cell biology", "Drugs and devices", "Drug research and development", "Pharmacodynamics", "Infectious diseases", "Prion diseases", "Veterinary diseases", "Zoonotic diseases", "sirna", "incubation"], "article_id"=>936388, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sylvain Lehmann", "Aroa Relaño-Ginès", "Sarah Resina", "Elsa Brillaud", "Danielle Casanova", "Charles Vincent", "Claire Hamela", "Sophie Poupeau", "Mathieu Laffont", "Audrey Gabelle", "Constance Delaby", "Maxime Belondrade", "Jacques-Damien Arnaud", "Maria-Teresa Alvarez", "Jean-Claude Maurel", "Patrick Maurel", "Carole Crozet"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0088797.g002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_siRNA_on_incubation_and_survival_time_/936388", "title"=>"Impact of siRNA on incubation and survival time.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-14 03:45:38"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
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  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
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Relative Metric

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