SrasV1, Main, Exploration, bibRecord, 005A85

Prophylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus

Identifieur interne : 005A85 ( Main/Exploration ); précédent : 005A84; suivant : 005A86

Prophylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus

Auteurs : Bo-Jian Zheng [Hong Kong] ; YI GUAN [Hong Kong] ; QINGQUAN TANG [États-Unis] ; DU CHENG [République populaire de Chine] ; Frank Yxie [États-Unis] ; Ming-Liang He [Hong Kong] ; Kwok-Wah Chan [Hong Kong] ; Kin-Ling Wong [Hong Kong] ; Eric Lader [États-Unis] ; Martin C. Woodle [États-Unis] ; Patrick Y. Lu [États-Unis] ; BAOJIAN LI [République populaire de Chine] ; NANSHAN ZHONG [République populaire de Chine]

Source :

Antiviral therapy : (London) [ 1359-6535 ] ; 2004.

RBID : Pascal:04-0440228

Descripteurs français

KwdFr :
- ARN viral (antagonistes et inhibiteurs), ARN viral (biosynthèse), Animaux, Antiviraux (synthèse chimique), Effet cytopathogène viral (physiologie), Facteurs temps, Génome viral, Lignée cellulaire, Macaca mulatta, Milieux de culture, Petit ARN interférent (génétique), Petit ARN interférent (synthèse chimique), RT-PCR, Réplication virale (génétique), Thérapie génétique, Transfection, Virus du SRAS (génétique), Virus du SRAS (isolement et purification), Virus du SRAS (physiologie).
MESH :
- antagonistes et inhibiteurs : ARN viral.
- biosynthèse : ARN viral.
- génétique : Petit ARN interférent, Réplication virale, Virus du SRAS.
- isolement et purification : Virus du SRAS.
- physiologie : Effet cytopathogène viral, Virus du SRAS.
- synthèse chimique : Antiviraux, Petit ARN interférent.
Pascal (Inist)
- Animaux, Facteurs temps, Génome viral, Lignée cellulaire, Macaca mulatta, Milieux de culture, Prévention, Cible, Ciblage, RT-PCR, Syndrome respiratoire aigu sévère, Coronavirus, Thérapie génétique, Traitement, In vitro, Transfection, siRNA, Antiviral.

English descriptors

KwdEn :
- Animals, Antiviral, Antiviral Agents (chemical synthesis), Cell Line, Coronavirus, Culture Media, Cytopathogenic Effect, Viral (physiology), Genetic Therapy, Genome, Viral, In vitro, Macaca mulatta, Prevention, RNA, Small Interfering (chemical synthesis), RNA, Small Interfering (genetics), RNA, Viral (antagonists & inhibitors), RNA, Viral (biosynthesis), Reverse Transcriptase Polymerase Chain Reaction, SARS Virus (genetics), SARS Virus (isolation & purification), SARS Virus (physiology), Severe acute respiratory syndrome, Small Interference RNA, Target, Targeting, Time Factors, Transfection, Treatment, Virus Replication (genetics).
MESH :
- chemical , antagonists & inhibitors : RNA, Viral.
- chemical , biosynthesis : RNA, Viral.
- chemical , chemical synthesis : Antiviral Agents, RNA, Small Interfering.
- chemical , genetics : RNA, Small Interfering.
- genetics : SARS Virus, Virus Replication.
- isolation & purification : SARS Virus.
- physiology : Cytopathogenic Effect, Viral, SARS Virus.
- Animals, Cell Line, Culture Media, Genetic Therapy, Genome, Viral, Macaca mulatta, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Transfection.

Abstract

Objectives: To identify and characterize the siRNA duplexes that are effective for inhibition of SARS-CoV infection and replication in the non-human primate cells. This in vitro study will serve as the foundation for development of novel anti-SARS therapeutics. Methods: 48 siRNA sequences were designed for targeting regions throughout entire SARS-CoV genome RNA including open-reading frames for several key proteins. Chemically synthesized siRNA duplexes were transfected into foetal rhesus kidney (FRhK-4) cells prior to or after SARS-CoV infection. The inhibitory effects of the siRNAs were evaluated for reductions of intracellular viral genome copy number and viral titres in the cell culture medium measured by Q-RT-PCR and CPE-based titration, respectively. Four siRNA duplexes were found to achieve potent inhibition of SARS-CoV infection and replication. A prolonged prophylactic effect of siRNA duplexes with up to 90% inhibition that lasted for at least 72 h was observed. Combination of active siRNA duplexes targeting different regions of the viral genome resulted in therapeutic activity of up to 80% inhibition. Conclusion: Chemically synthesized siRNA duplexes targeting SARS-CoV genomic RNA are potent agents for inhibition of the viral infection and replication. The location effects of siRNAs were revealed at both genome sequence and open-reading frame levels. The rapid development of siRNA-based SARS-CoV inhibitors marked a novel approach for combating newly emergent infectious diseases.

Affiliations:

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Prophylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus</title>
<author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name>
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<author><name sortKey="Qingquan Tang" sort="Qingquan Tang" uniqKey="Qingquan Tang" last="Qingquan Tang">QINGQUAN TANG</name>
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<author><name sortKey="Du Cheng" sort="Du Cheng" uniqKey="Du Cheng" last="Du Cheng">DU CHENG</name>
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<author><name sortKey="He, Ming Liang" sort="He, Ming Liang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</name>
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<author><name sortKey="Chan, Kwok Wah" sort="Chan, Kwok Wah" uniqKey="Chan K" first="Kwok-Wah" last="Chan">Kwok-Wah Chan</name>
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<author><name sortKey="Wong, Kin Ling" sort="Wong, Kin Ling" uniqKey="Wong K" first="Kin-Ling" last="Wong">Kin-Ling Wong</name>
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<author><name sortKey="Lader, Eric" sort="Lader, Eric" uniqKey="Lader E" first="Eric" last="Lader">Eric Lader</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Qiagen Sciences, Inc.</s1>
<s2>Germantown, Md.</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Germantown, Md.</wicri:noRegion>
</affiliation>
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<author><name sortKey="Woodle, Martin C" sort="Woodle, Martin C" uniqKey="Woodle M" first="Martin C." last="Woodle">Martin C. Woodle</name>
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<author><name sortKey="Lu, Patrick Y" sort="Lu, Patrick Y" uniqKey="Lu P" first="Patrick Y." last="Lu">Patrick Y. Lu</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Intradigm Corporation</s1>
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<wicri:noRegion>Intradigm Corporation</wicri:noRegion>
</affiliation>
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<author><name sortKey="Baojian Li" sort="Baojian Li" uniqKey="Baojian Li" last="Baojian Li">BAOJIAN LI</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Guangzhou Top Genomics, Ltd</s1>
<s2>Guangzhou</s2>
<s3>CHN</s3>
<sZ>4 aut.</sZ>
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</inist:fA14>
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<placeName><settlement type="city">Jiangmen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Biotechnology Research Center of Sun Yatsen University, and Key Laboratory of Gene Engineering of Ministry of Education of China, Department of Education of the State</s1>
<s2>Guangzhou</s2>
<s3>CHN</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName><settlement type="city">Jiangmen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nanshan Zhong" sort="Nanshan Zhong" uniqKey="Nanshan Zhong" last="Nanshan Zhong">NANSHAN ZHONG</name>
<affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Guangzhou Institute of Respiratory Diseases</s1>
<s2>Guangzhou</s2>
<s3>CHN</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName><settlement type="city">Jiangmen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Antiviral therapy : (London)</title>
<title level="j" type="abbreviated">Antivir. ther. : (Lond.)</title>
<idno type="ISSN">1359-6535</idno>
<imprint><date when="2004">2004</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Antiviral therapy : (London)</title>
<title level="j" type="abbreviated">Antivir. ther. : (Lond.)</title>
<idno type="ISSN">1359-6535</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Antiviral</term>
<term>Antiviral Agents (chemical synthesis)</term>
<term>Cell Line</term>
<term>Coronavirus</term>
<term>Culture Media</term>
<term>Cytopathogenic Effect, Viral (physiology)</term>
<term>Genetic Therapy</term>
<term>Genome, Viral</term>
<term>In vitro</term>
<term>Macaca mulatta</term>
<term>Prevention</term>
<term>RNA, Small Interfering (chemical synthesis)</term>
<term>RNA, Small Interfering (genetics)</term>
<term>RNA, Viral (antagonists & inhibitors)</term>
<term>RNA, Viral (biosynthesis)</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (isolation & purification)</term>
<term>SARS Virus (physiology)</term>
<term>Severe acute respiratory syndrome</term>
<term>Small Interference RNA</term>
<term>Target</term>
<term>Targeting</term>
<term>Time Factors</term>
<term>Transfection</term>
<term>Treatment</term>
<term>Virus Replication (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral (antagonistes et inhibiteurs)</term>
<term>ARN viral (biosynthèse)</term>
<term>Animaux</term>
<term>Antiviraux (synthèse chimique)</term>
<term>Effet cytopathogène viral (physiologie)</term>
<term>Facteurs temps</term>
<term>Génome viral</term>
<term>Lignée cellulaire</term>
<term>Macaca mulatta</term>
<term>Milieux de culture</term>
<term>Petit ARN interférent (génétique)</term>
<term>Petit ARN interférent (synthèse chimique)</term>
<term>RT-PCR</term>
<term>Réplication virale (génétique)</term>
<term>Thérapie génétique</term>
<term>Transfection</term>
<term>Virus du SRAS (génétique)</term>
<term>Virus du SRAS (isolement et purification)</term>
<term>Virus du SRAS (physiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>RNA, Viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>RNA, Viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Antiviral Agents</term>
<term>RNA, Small Interfering</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Small Interfering</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>ARN viral</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>ARN viral</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Petit ARN interférent</term>
<term>Réplication virale</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Effet cytopathogène viral</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Cytopathogenic Effect, Viral</term>
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Antiviraux</term>
<term>Petit ARN interférent</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Line</term>
<term>Culture Media</term>
<term>Genetic Therapy</term>
<term>Genome, Viral</term>
<term>Macaca mulatta</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
<term>Time Factors</term>
<term>Transfection</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term>
<term>Facteurs temps</term>
<term>Génome viral</term>
<term>Lignée cellulaire</term>
<term>Macaca mulatta</term>
<term>Milieux de culture</term>
<term>Prévention</term>
<term>Cible</term>
<term>Ciblage</term>
<term>RT-PCR</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Coronavirus</term>
<term>Thérapie génétique</term>
<term>Traitement</term>
<term>In vitro</term>
<term>Transfection</term>
<term>siRNA</term>
<term>Antiviral</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Objectives: To identify and characterize the siRNA duplexes that are effective for inhibition of SARS-CoV infection and replication in the non-human primate cells. This in vitro study will serve as the foundation for development of novel anti-SARS therapeutics. Methods: 48 siRNA sequences were designed for targeting regions throughout entire SARS-CoV genome RNA including open-reading frames for several key proteins. Chemically synthesized siRNA duplexes were transfected into foetal rhesus kidney (FRhK-4) cells prior to or after SARS-CoV infection. The inhibitory effects of the siRNAs were evaluated for reductions of intracellular viral genome copy number and viral titres in the cell culture medium measured by Q-RT-PCR and CPE-based titration, respectively. Four siRNA duplexes were found to achieve potent inhibition of SARS-CoV infection and replication. A prolonged prophylactic effect of siRNA duplexes with up to 90% inhibition that lasted for at least 72 h was observed. Combination of active siRNA duplexes targeting different regions of the viral genome resulted in therapeutic activity of up to 80% inhibition. Conclusion: Chemically synthesized siRNA duplexes targeting SARS-CoV genomic RNA are potent agents for inhibition of the viral infection and replication. The location effects of siRNAs were revealed at both genome sequence and open-reading frame levels. The rapid development of siRNA-based SARS-CoV inhibitors marked a novel approach for combating newly emergent infectious diseases.</div>
</front>
</TEI>
<affiliations><list><country><li>Hong Kong</li>
<li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Guangdong</li>
</region>
<settlement><li>Jiangmen</li>
</settlement>
</list>
<tree><country name="Hong Kong"><noRegion><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name>
</noRegion>
<name sortKey="Chan, Kwok Wah" sort="Chan, Kwok Wah" uniqKey="Chan K" first="Kwok-Wah" last="Chan">Kwok-Wah Chan</name>
<name sortKey="He, Ming Liang" sort="He, Ming Liang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</name>
<name sortKey="Wong, Kin Ling" sort="Wong, Kin Ling" uniqKey="Wong K" first="Kin-Ling" last="Wong">Kin-Ling Wong</name>
<name sortKey="Yi Guan" sort="Yi Guan" uniqKey="Yi Guan" last="Yi Guan">YI GUAN</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Qingquan Tang" sort="Qingquan Tang" uniqKey="Qingquan Tang" last="Qingquan Tang">QINGQUAN TANG</name>
</noRegion>
<name sortKey="Lader, Eric" sort="Lader, Eric" uniqKey="Lader E" first="Eric" last="Lader">Eric Lader</name>
<name sortKey="Lu, Patrick Y" sort="Lu, Patrick Y" uniqKey="Lu P" first="Patrick Y." last="Lu">Patrick Y. Lu</name>
<name sortKey="Woodle, Martin C" sort="Woodle, Martin C" uniqKey="Woodle M" first="Martin C." last="Woodle">Martin C. Woodle</name>
<name sortKey="Yxie, Frank" sort="Yxie, Frank" uniqKey="Yxie F" first="Frank" last="Yxie">Frank Yxie</name>
</country>
<country name="République populaire de Chine"><region name="Guangdong"><name sortKey="Du Cheng" sort="Du Cheng" uniqKey="Du Cheng" last="Du Cheng">DU CHENG</name>
</region>
<name sortKey="Baojian Li" sort="Baojian Li" uniqKey="Baojian Li" last="Baojian Li">BAOJIAN LI</name>
<name sortKey="Baojian Li" sort="Baojian Li" uniqKey="Baojian Li" last="Baojian Li">BAOJIAN LI</name>
<name sortKey="Nanshan Zhong" sort="Nanshan Zhong" uniqKey="Nanshan Zhong" last="Nanshan Zhong">NANSHAN ZHONG</name>
</country>
</tree>
</affiliations>
</record>

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Prophylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus

Prophylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus

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