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Article: Liver as an ideal target for gene therapy: Expression of CTLA4Ig by retroviral gene transfer

TitleLiver as an ideal target for gene therapy: Expression of CTLA4Ig by retroviral gene transfer
Authors
KeywordsCTLA4Ig
Gene therapy
Gene transfer techniques
Liver transplantation
Retrovirus
Issue Date2002
PublisherWiley-Blackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JGH
Citation
Journal Of Gastroenterology And Hepatology, 2002, v. 17 n. 9, p. 1008-1014 How to Cite?
AbstractBackground and Aims: Liver has been a target organ for gene therapy as it plays a central role in metabolism and production of serum proteins. Many metabolic disorders result from a deficiency of liver-derived protein products. In transplantation settings, modulation of the immune responses caused by CTLA4Ig protein has been shown to be an attractive direction. In this study, we investigated the efficacy of hepatocyte transduction via introduction of the exogenous CTLA4Ig gene to the rat liver graft by retrovirus vector, and examined the presence of target serum protein after gene transfers. Methods: We constructed a replication defective retroviral vector that contained the CTLA4Ig gene. The liver graft regeneration index was first examined by 5-bromo-2-deoxyuridine, Ki-67 and proliferating cell nuclear antigen antibodies to determine the optimal time of gene transduction. The liver graft was then perfused with the retroviral vector, and animals were killed at constant time points to examine for the presence of CTLA4 protein in the graft and peripheral blood. Results: CTLA4 protein was detected on postoperative days 5, 9 and 14, with liver graft tissue transduction indexes of 7.2, 10.9 and 1.8, respectively. Blood protein levels were at 151.6, 26.5 and 21.4 ρg/mL, respectively. A transduction index reaching 22.1 was observed in the graft with the most rapid liver regeneration. Conclusions: We had established the gene delivery model in rat with auxiliary partial liver transplantation. Expression of the exogenous gene delivered by retrovirus was demonstrated in the liver with secretion of diffusible protein in the bloodstream. The present study provides important information for gene transfer using the liver to produce the target protein in situ and as serum protein. This will also be applicable to the treatment of other metabolic diseases. © 2002 Blackwell Publishing Asia Pty Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/83112
ISSN
2015 Impact Factor: 3.322
2015 SCImago Journal Rankings: 1.190
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheung, STen_HK
dc.contributor.authorTsui, TYen_HK
dc.contributor.authorWang, WLen_HK
dc.contributor.authorYang, ZFen_HK
dc.contributor.authorWong, SYen_HK
dc.contributor.authorIp, YCen_HK
dc.contributor.authorLuk, Jen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-06T08:37:09Z-
dc.date.available2010-09-06T08:37:09Z-
dc.date.issued2002en_HK
dc.identifier.citationJournal Of Gastroenterology And Hepatology, 2002, v. 17 n. 9, p. 1008-1014en_HK
dc.identifier.issn0815-9319en_HK
dc.identifier.urihttp://hdl.handle.net/10722/83112-
dc.description.abstractBackground and Aims: Liver has been a target organ for gene therapy as it plays a central role in metabolism and production of serum proteins. Many metabolic disorders result from a deficiency of liver-derived protein products. In transplantation settings, modulation of the immune responses caused by CTLA4Ig protein has been shown to be an attractive direction. In this study, we investigated the efficacy of hepatocyte transduction via introduction of the exogenous CTLA4Ig gene to the rat liver graft by retrovirus vector, and examined the presence of target serum protein after gene transfers. Methods: We constructed a replication defective retroviral vector that contained the CTLA4Ig gene. The liver graft regeneration index was first examined by 5-bromo-2-deoxyuridine, Ki-67 and proliferating cell nuclear antigen antibodies to determine the optimal time of gene transduction. The liver graft was then perfused with the retroviral vector, and animals were killed at constant time points to examine for the presence of CTLA4 protein in the graft and peripheral blood. Results: CTLA4 protein was detected on postoperative days 5, 9 and 14, with liver graft tissue transduction indexes of 7.2, 10.9 and 1.8, respectively. Blood protein levels were at 151.6, 26.5 and 21.4 ρg/mL, respectively. A transduction index reaching 22.1 was observed in the graft with the most rapid liver regeneration. Conclusions: We had established the gene delivery model in rat with auxiliary partial liver transplantation. Expression of the exogenous gene delivered by retrovirus was demonstrated in the liver with secretion of diffusible protein in the bloodstream. The present study provides important information for gene transfer using the liver to produce the target protein in situ and as serum protein. This will also be applicable to the treatment of other metabolic diseases. © 2002 Blackwell Publishing Asia Pty Ltd.en_HK
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JGHen_HK
dc.relation.ispartofJournal of Gastroenterology and Hepatologyen_HK
dc.subjectCTLA4Igen_HK
dc.subjectGene therapyen_HK
dc.subjectGene transfer techniquesen_HK
dc.subjectLiver transplantationen_HK
dc.subjectRetrovirusen_HK
dc.titleLiver as an ideal target for gene therapy: Expression of CTLA4Ig by retroviral gene transferen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0815-9319&volume=17 &issue=9&spage=1008&epage=1014&date=2002&atitle=Liver+as+an+ideal+target+for+gene+therapy:+expression+of+CTLA4Ig+by+retroviral+gene+transferen_HK
dc.identifier.emailCheung, ST: stcheung@hkucc.hku.hken_HK
dc.identifier.emailLuk, J: jmluk@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityCheung, ST=rp00457en_HK
dc.identifier.authorityLuk, J=rp00349en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1046/j.1440-1746.2002.02784.xen_HK
dc.identifier.pmid12167123-
dc.identifier.scopuseid_2-s2.0-0036379782en_HK
dc.identifier.hkuros82561en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036379782&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume17en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1008en_HK
dc.identifier.epage1014en_HK
dc.identifier.isiWOS:000179400700013-
dc.publisher.placeAustraliaen_HK
dc.identifier.scopusauthoridCheung, ST=7202473497en_HK
dc.identifier.scopusauthoridTsui, TY=7006622455en_HK
dc.identifier.scopusauthoridWang, WL=7501756106en_HK
dc.identifier.scopusauthoridYang, ZF=14018809600en_HK
dc.identifier.scopusauthoridWong, SY=7404590342en_HK
dc.identifier.scopusauthoridIp, YC=36943517300en_HK
dc.identifier.scopusauthoridLuk, J=7006777791en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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