Inhibition of HBV gene expression and replication by stably expressed interferon‐α1 via adeno‐associated viral vectors
Identifieur interne : 003347 ( Main/Exploration ); précédent : 003346; suivant : 003348Inhibition of HBV gene expression and replication by stably expressed interferon‐α1 via adeno‐associated viral vectors
Auteurs : Zhi Li [République populaire de Chine] ; Hong Yao [République populaire de Chine] ; Yan Ma [République populaire de Chine] ; Qingming Dong [République populaire de Chine] ; Yangchao Chen [République populaire de Chine] ; Ying Peng [République populaire de Chine] ; Bo-Jian Zheng [République populaire de Chine] ; Jian-Dong Huang [République populaire de Chine] ; Chu-Yan Chan [République populaire de Chine] ; Marie C. Lin [République populaire de Chine] ; Joseph J. Sung [République populaire de Chine] ; Kwok Yun Yuen [République populaire de Chine] ; Hsiang-Fu Kung [République populaire de Chine, Hong Kong] ; Ming-Liang He [République populaire de Chine, Hong Kong]Source :
- The Journal of Gene Medicine [ 1099-498X ] ; 2008-06.
English descriptors
- Teeft :
- Aav2, Aav2 vector, Acute hepatitis, Antiviral, Antiviral activity, Antiviral effects, Biochem biophys, Carcinoma, Cdna encoding, Cell line, Cells transduced, Chinese university, Chronic hepatitis, Clinical outcome, Clinical trials, Colon cancer, Copyright, Culture media, Cytokine growth factor, Different time points, East asia, Egfp, Egfp expression level, Elisa, Expression level, Gene, Gene expression, Gene therapy, Gene transfer, Genotype, Hbeag, Hbeag levels, Hbsag, Hbsag level, Hepatitis, Hepatocellular, Hepatocellular carcinoma, High level, Hong kong, Hydrodynamic, Hydrodynamic transfection, Hydrodynamic transfection mouse model, Ifns, Immunocompetent mice, Immunocytochemical studies, Immunosorbent assay, Infectious diseases, Interferon, Interferon therapy, John wiley sons, Liver cells, Liver sections, Local expression, Major concerns, Middle panels, Mouse model, Multiple sclerosis, Nude mice, Obvious liver damage, Other genotypes, Other hand, Papillomavirus infections, Phylogenetic relatedness, Present study, Previous studies, Proc natl acad, Public health, Raav, Raav vectors, Replication, Secondary antibody, Several passages, Transduction, Transgene expression, Transgenic mice, Unpublished data, Uorescence, Uorescence microscope, Uorescent signals, Viral, Viral infections, Viral load, Viral loads, Viral replication, Virus genotype, Virus infection.
Abstract
Background: Interferon‐α2 (IFNα2) is routinely used for anti‐hepatitis B virus (HBV) treatment. However, the therapeutic efficiency is unsatisfactory, particularly in East Asia. Such inefficiency might be a result of the short half‐life, relatively low local concentration and strong side‐effects of interferons. Frequent and repeated injection is also a big burden for patients. In the present study, a single dose of vector‐delivered IFNα1 was tested for its anti‐HBV effects. Methods: Adeno‐associated viral vector (AAV‐IFNα1) was generated to deliver the IFNα1 gene into hepatocytes. IFNα1, hepatitis B surface (HBsAg) and e (HBeAg) antigens were measured by enzyme‐linked immunosorbent assay and/or western blotting. The level of viral DNA was measured by quantitative real‐time polymerase chain reaction. Results: AAV‐IFNα1 effectively transduced HBV‐producing cells (HepAD38) and mouse hepatocytes, where IFNα1 was expressed in a stable manner. Both intracellular and extracellular HBsAg and HBeAg were significantly reduced in vitro. In the HBV‐producing mice, the concentration of IFNα1 in the liver was eight‐fold higher than that in plasma. Compared with control groups, HBeAg/HBsAg antigen levels were reduced by more than ten‐fold from day 1–5, and dropped to an undetectable level on day 9 in the AAV‐IFNα1 group. Concurrently, the level of viral DNA decreased over 30‐fold for several weeks. Conclusions: A single dose administration of AAV‐IFNα1 viral vector displayed prolonged transgene expression and superior antiviral effects both in vitro and in vivo. Therefore, the use of AAV‐IFNα1 might be a potential alternative strategy for anti‐HBV therapy. Copyright © 2008 John Wiley & Sons, Ltd.
Url:
DOI: 10.1002/jgm.1174
Affiliations:
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Lin</name></author><author><name sortKey="Sung, Joseph J" sort="Sung, Joseph J" uniqKey="Sung J" first="Joseph J" last="Sung">Joseph J. 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wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Chemistry, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Yan" sort="Ma, Yan" uniqKey="Ma Y" first="Yan" last="Ma">Yan Ma</name><affiliation wicri:level="4"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Dong, Qingming" sort="Dong, Qingming" uniqKey="Dong Q" first="Qingming" last="Dong">Qingming Dong</name><affiliation wicri:level="4"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Chen, Yangchao" sort="Chen, Yangchao" uniqKey="Chen Y" first="Yangchao" last="Chen">Yangchao Chen</name><affiliation wicri:level="4"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Peng, Ying" sort="Peng, Ying" uniqKey="Peng Y" first="Ying" last="Peng">Ying Peng</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, The Second Affiliated Hospital, Sun Yat‐sen University, Guangzhou, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Zheng, Bo Ian" sort="Zheng, Bo Ian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Jian Ong" sort="Huang, Jian Ong" uniqKey="Huang J" first="Jian-Dong" last="Huang">Jian-Dong Huang</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Chu An" sort="Chan, Chu An" uniqKey="Chan C" first="Chu-Yan" last="Chan">Chu-Yan Chan</name><affiliation wicri:level="4"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Lin, Marie C" sort="Lin, Marie C" uniqKey="Lin M" first="Marie C." last="Lin">Marie C. Lin</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Chemistry, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Sung, Joseph J" sort="Sung, Joseph J" uniqKey="Sung J" first="Joseph J" last="Sung">Joseph J. Sung</name><affiliation wicri:level="4"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Yuen, Kwok Yun" sort="Yuen, Kwok Yun" uniqKey="Yuen K" first="Kwok Yun" last="Yuen">Kwok Yun Yuen</name><affiliation wicri:level="1"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Kung, Hsiang U" sort="Kung, Hsiang U" uniqKey="Kung H" first="Hsiang-Fu" last="Kung">Hsiang-Fu Kung</name><affiliation wicri:level="4"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Hong Kong</country></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Hong Kong</country><wicri:regionArea>Correspondence address: Stanley Ho Center for Emerging Infectious Diseases, School of Public Health, The Chinese University of Hong Kong, Satin, NT</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="He, Ming Iang" sort="He, Ming Iang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</name><affiliation wicri:level="4"><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Stanley Ho Center for Emerging Infectious Diseases, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Hong Kong</country></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Hong Kong</country><wicri:regionArea>Correspondence address: Stanley Ho Center for Emerging Infectious Diseases, School of Public Health, The Chinese University of Hong Kong, Satin, NT</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The Journal of Gene Medicine</title><title level="j" type="alt">JOURNAL OF GENE MEDICINE, THE</title><idno type="ISSN">1099-498X</idno><idno type="eISSN">1521-2254</idno><imprint><biblScope unit="vol">10</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="619">619</biblScope><biblScope unit="page" to="627">627</biblScope><biblScope unit="page-count">9</biblScope><publisher>John Wiley & Sons, Ltd.</publisher><pubPlace>Chichester, UK</pubPlace><date type="published" when="2008-06">2008-06</date></imprint><idno type="ISSN">1099-498X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1099-498X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Aav2</term><term>Aav2 vector</term><term>Acute hepatitis</term><term>Antiviral</term><term>Antiviral activity</term><term>Antiviral effects</term><term>Biochem biophys</term><term>Carcinoma</term><term>Cdna encoding</term><term>Cell line</term><term>Cells transduced</term><term>Chinese university</term><term>Chronic hepatitis</term><term>Clinical outcome</term><term>Clinical trials</term><term>Colon cancer</term><term>Copyright</term><term>Culture media</term><term>Cytokine growth factor</term><term>Different time points</term><term>East asia</term><term>Egfp</term><term>Egfp expression level</term><term>Elisa</term><term>Expression level</term><term>Gene</term><term>Gene expression</term><term>Gene therapy</term><term>Gene transfer</term><term>Genotype</term><term>Hbeag</term><term>Hbeag levels</term><term>Hbsag</term><term>Hbsag level</term><term>Hepatitis</term><term>Hepatocellular</term><term>Hepatocellular carcinoma</term><term>High level</term><term>Hong kong</term><term>Hydrodynamic</term><term>Hydrodynamic transfection</term><term>Hydrodynamic transfection mouse model</term><term>Ifns</term><term>Immunocompetent mice</term><term>Immunocytochemical studies</term><term>Immunosorbent assay</term><term>Infectious diseases</term><term>Interferon</term><term>Interferon therapy</term><term>John wiley sons</term><term>Liver cells</term><term>Liver sections</term><term>Local expression</term><term>Major concerns</term><term>Middle panels</term><term>Mouse model</term><term>Multiple sclerosis</term><term>Nude mice</term><term>Obvious liver damage</term><term>Other genotypes</term><term>Other hand</term><term>Papillomavirus infections</term><term>Phylogenetic relatedness</term><term>Present study</term><term>Previous studies</term><term>Proc natl acad</term><term>Public health</term><term>Raav</term><term>Raav vectors</term><term>Replication</term><term>Secondary antibody</term><term>Several passages</term><term>Transduction</term><term>Transgene expression</term><term>Transgenic mice</term><term>Unpublished data</term><term>Uorescence</term><term>Uorescence microscope</term><term>Uorescent signals</term><term>Viral</term><term>Viral infections</term><term>Viral load</term><term>Viral loads</term><term>Viral replication</term><term>Virus genotype</term><term>Virus infection</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Interferon‐α2 (IFNα2) is routinely used for anti‐hepatitis B virus (HBV) treatment. However, the therapeutic efficiency is unsatisfactory, particularly in East Asia. Such inefficiency might be a result of the short half‐life, relatively low local concentration and strong side‐effects of interferons. Frequent and repeated injection is also a big burden for patients. In the present study, a single dose of vector‐delivered IFNα1 was tested for its anti‐HBV effects. Methods: Adeno‐associated viral vector (AAV‐IFNα1) was generated to deliver the IFNα1 gene into hepatocytes. IFNα1, hepatitis B surface (HBsAg) and e (HBeAg) antigens were measured by enzyme‐linked immunosorbent assay and/or western blotting. The level of viral DNA was measured by quantitative real‐time polymerase chain reaction. Results: AAV‐IFNα1 effectively transduced HBV‐producing cells (HepAD38) and mouse hepatocytes, where IFNα1 was expressed in a stable manner. Both intracellular and extracellular HBsAg and HBeAg were significantly reduced in vitro. In the HBV‐producing mice, the concentration of IFNα1 in the liver was eight‐fold higher than that in plasma. Compared with control groups, HBeAg/HBsAg antigen levels were reduced by more than ten‐fold from day 1–5, and dropped to an undetectable level on day 9 in the AAV‐IFNα1 group. Concurrently, the level of viral DNA decreased over 30‐fold for several weeks. Conclusions: A single dose administration of AAV‐IFNα1 viral vector displayed prolonged transgene expression and superior antiviral effects both in vitro and in vivo. Therefore, the use of AAV‐IFNα1 might be a potential alternative strategy for anti‐HBV therapy. Copyright © 2008 John Wiley & Sons, Ltd.</div></front></TEI><affiliations><list><country><li>Hong Kong</li><li>République populaire de Chine</li></country><settlement><li>Sha Tin</li></settlement><orgName><li>Université chinoise de Hong Kong</li></orgName></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Li, Zhi" sort="Li, Zhi" uniqKey="Li Z" first="Zhi" last="Li">Zhi Li</name></noRegion><name sortKey="Chan, Chu An" sort="Chan, Chu An" uniqKey="Chan C" first="Chu-Yan" last="Chan">Chu-Yan Chan</name><name sortKey="Chen, Yangchao" sort="Chen, Yangchao" uniqKey="Chen Y" first="Yangchao" last="Chen">Yangchao Chen</name><name sortKey="Dong, Qingming" sort="Dong, Qingming" uniqKey="Dong Q" first="Qingming" last="Dong">Qingming Dong</name><name sortKey="He, Ming Iang" sort="He, Ming Iang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</name><name sortKey="Huang, Jian Ong" sort="Huang, Jian Ong" uniqKey="Huang J" first="Jian-Dong" last="Huang">Jian-Dong Huang</name><name sortKey="Kung, Hsiang U" sort="Kung, Hsiang U" uniqKey="Kung H" first="Hsiang-Fu" last="Kung">Hsiang-Fu Kung</name><name sortKey="Lin, Marie C" sort="Lin, Marie C" uniqKey="Lin M" first="Marie C." last="Lin">Marie C. Lin</name><name sortKey="Ma, Yan" sort="Ma, Yan" uniqKey="Ma Y" first="Yan" last="Ma">Yan Ma</name><name sortKey="Peng, Ying" sort="Peng, Ying" uniqKey="Peng Y" first="Ying" last="Peng">Ying Peng</name><name sortKey="Sung, Joseph J" sort="Sung, Joseph J" uniqKey="Sung J" first="Joseph J" last="Sung">Joseph J. Sung</name><name sortKey="Yao, Hong" sort="Yao, Hong" uniqKey="Yao H" first="Hong" last="Yao">Hong Yao</name><name sortKey="Yuen, Kwok Yun" sort="Yuen, Kwok Yun" uniqKey="Yuen K" first="Kwok Yun" last="Yuen">Kwok Yun Yuen</name><name sortKey="Zheng, Bo Ian" sort="Zheng, Bo Ian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name></country><country name="Hong Kong"><noRegion><name sortKey="Kung, Hsiang U" sort="Kung, Hsiang U" uniqKey="Kung H" first="Hsiang-Fu" last="Kung">Hsiang-Fu Kung</name></noRegion><name sortKey="He, Ming Iang" sort="He, Ming Iang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</name><name sortKey="He, Ming Iang" sort="He, Ming Iang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</name><name sortKey="Kung, Hsiang U" sort="Kung, Hsiang U" uniqKey="Kung H" first="Hsiang-Fu" last="Kung">Hsiang-Fu Kung</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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