Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque.
Identifieur interne : 004567 ( Main/Exploration ); précédent : 004566; suivant : 004568Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque.
Auteurs : Bao-Jian Li [République populaire de Chine] ; Qingquan Tang ; Du Cheng ; Chuan Qin ; Frank Y. Xie ; Qiang Wei ; Jun Xu ; Yijia Liu ; Bo-Jian Zheng ; Martin C. Woodle ; Nanshan Zhong ; Patrick Y. LuSource :
- Nature medicine [ 1078-8956 ] ; 2005.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (usage thérapeutique), Données de séquences moléculaires, Femelle, Génome viral, Macaca mulatta, Mâle, Petit ARN interférent (usage thérapeutique), Poumon (), Poumon (anatomopathologie), Poumon (virologie), Relation dose-effet des médicaments, Souris, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (anatomopathologie), Syndrome respiratoire aigu sévère (traitement médicamenteux), Virus du SRAS ().
- MESH :
- anatomopathologie : Poumon, Syndrome respiratoire aigu sévère.
- traitement médicamenteux : Syndrome respiratoire aigu sévère.
- usage thérapeutique : Antiviraux, Petit ARN interférent.
- virologie : Poumon.
- Animaux, Données de séquences moléculaires, Femelle, Génome viral, Macaca mulatta, Mâle, Poumon, Relation dose-effet des médicaments, Souris, Syndrome respiratoire aigu sévère, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (therapeutic use), Dose-Response Relationship, Drug, Female, Genome, Viral, Lung (drug effects), Lung (pathology), Lung (virology), Macaca mulatta, Male, Mice, Molecular Sequence Data, RNA, Small Interfering (therapeutic use), SARS Virus (drug effects), Severe Acute Respiratory Syndrome (drug therapy), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (prevention & control).
- MESH :
- chemical , therapeutic use : Antiviral Agents, RNA, Small Interfering.
- drug effects : Lung, SARS Virus.
- drug therapy : Severe Acute Respiratory Syndrome.
- pathology : Lung, Severe Acute Respiratory Syndrome.
- prevention & control : Severe Acute Respiratory Syndrome.
- virology : Lung.
- Animals, Dose-Response Relationship, Drug, Female, Genome, Viral, Macaca mulatta, Male, Mice, Molecular Sequence Data.
Abstract
Development of therapeutic agents for severe acute respiratory syndrome (SARS) viral infection using short interfering RNA (siRNA) inhibitors exemplifies a powerful new means to combat emerging infectious diseases. Potent siRNA inhibitors of SARS coronavirus (SCV) in vitro were further evaluated for efficacy and safety in a rhesus macaque (Macaca mulatta) SARS model using clinically viable delivery while comparing three dosing regimens. Observations of SARS-like symptoms, measurements of SCV RNA presence and lung histopathology and immunohistochemistry consistently showed siRNA-mediated anti-SARS efficacy by either prophylactic or therapeutic regimens. The siRNAs used provided relief from SCV infection-induced fever, diminished SCV viral levels and reduced acute diffuse alveoli damage. The 10-40 mg/kg accumulated dosages of siRNA did not show any sign of siRNA-induced toxicity. These results suggest that a clinical investigation is warranted and illustrate the prospects for siRNA to enable a massive reduction in development time for new targeted therapeutic agents.
DOI: 10.1038/nm1280
PubMed: 16116432
Affiliations:
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Le document en format XML
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Xie</name></author><author><name sortKey="Wei, Qiang" sort="Wei, Qiang" uniqKey="Wei Q" first="Qiang" last="Wei">Qiang Wei</name></author><author><name sortKey="Xu, Jun" sort="Xu, Jun" uniqKey="Xu J" first="Jun" last="Xu">Jun Xu</name></author><author><name sortKey="Liu, Yijia" sort="Liu, Yijia" uniqKey="Liu Y" first="Yijia" last="Liu">Yijia Liu</name></author><author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name></author><author><name sortKey="Woodle, Martin C" sort="Woodle, Martin C" uniqKey="Woodle M" first="Martin C" last="Woodle">Martin C. Woodle</name></author><author><name sortKey="Zhong, Nanshan" sort="Zhong, Nanshan" uniqKey="Zhong N" first="Nanshan" last="Zhong">Nanshan Zhong</name></author><author><name sortKey="Lu, Patrick Y" sort="Lu, Patrick Y" uniqKey="Lu P" first="Patrick Y" last="Lu">Patrick Y. 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Xie</name></author><author><name sortKey="Wei, Qiang" sort="Wei, Qiang" uniqKey="Wei Q" first="Qiang" last="Wei">Qiang Wei</name></author><author><name sortKey="Xu, Jun" sort="Xu, Jun" uniqKey="Xu J" first="Jun" last="Xu">Jun Xu</name></author><author><name sortKey="Liu, Yijia" sort="Liu, Yijia" uniqKey="Liu Y" first="Yijia" last="Liu">Yijia Liu</name></author><author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name></author><author><name sortKey="Woodle, Martin C" sort="Woodle, Martin C" uniqKey="Woodle M" first="Martin C" last="Woodle">Martin C. Woodle</name></author><author><name sortKey="Zhong, Nanshan" sort="Zhong, Nanshan" uniqKey="Zhong N" first="Nanshan" last="Zhong">Nanshan Zhong</name></author><author><name sortKey="Lu, Patrick Y" sort="Lu, Patrick Y" uniqKey="Lu P" first="Patrick Y" last="Lu">Patrick Y. 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Potent siRNA inhibitors of SARS coronavirus (SCV) in vitro were further evaluated for efficacy and safety in a rhesus macaque (Macaca mulatta) SARS model using clinically viable delivery while comparing three dosing regimens. Observations of SARS-like symptoms, measurements of SCV RNA presence and lung histopathology and immunohistochemistry consistently showed siRNA-mediated anti-SARS efficacy by either prophylactic or therapeutic regimens. The siRNAs used provided relief from SCV infection-induced fever, diminished SCV viral levels and reduced acute diffuse alveoli damage. The 10-40 mg/kg accumulated dosages of siRNA did not show any sign of siRNA-induced toxicity. These results suggest that a clinical investigation is warranted and illustrate the prospects for siRNA to enable a massive reduction in development time for new targeted therapeutic agents.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Guangdong</li></region><settlement><li>Jiangmen</li></settlement></list><tree><noCountry><name sortKey="Cheng, Du" sort="Cheng, Du" uniqKey="Cheng D" first="Du" last="Cheng">Du Cheng</name><name sortKey="Liu, Yijia" sort="Liu, Yijia" uniqKey="Liu Y" first="Yijia" last="Liu">Yijia Liu</name><name sortKey="Lu, Patrick Y" sort="Lu, Patrick Y" uniqKey="Lu P" first="Patrick Y" last="Lu">Patrick Y. Lu</name><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><name sortKey="Tang, Qingquan" sort="Tang, Qingquan" uniqKey="Tang Q" first="Qingquan" last="Tang">Qingquan Tang</name><name sortKey="Wei, Qiang" sort="Wei, Qiang" uniqKey="Wei Q" first="Qiang" last="Wei">Qiang Wei</name><name sortKey="Woodle, Martin C" sort="Woodle, Martin C" uniqKey="Woodle M" first="Martin C" last="Woodle">Martin C. Woodle</name><name sortKey="Xie, Frank Y" sort="Xie, Frank Y" uniqKey="Xie F" first="Frank Y" last="Xie">Frank Y. Xie</name><name sortKey="Xu, Jun" sort="Xu, Jun" uniqKey="Xu J" first="Jun" last="Xu">Jun Xu</name><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name><name sortKey="Zhong, Nanshan" sort="Zhong, Nanshan" uniqKey="Zhong N" first="Nanshan" last="Zhong">Nanshan Zhong</name></noCountry><country name="République populaire de Chine"><region name="Guangdong"><name sortKey="Li, Bao Jian" sort="Li, Bao Jian" uniqKey="Li B" first="Bao-Jian" last="Li">Bao-Jian Li</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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