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Article: Recombinant adeno-associated virus vector: Is it ideal for gene delivery in liver transplantation?

TitleRecombinant adeno-associated virus vector: Is it ideal for gene delivery in liver transplantation?
Authors
Issue Date2003
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jtoc/106570021
Citation
Liver Transplantation, 2003, v. 9 n. 4, p. 411-420 How to Cite?
AbstractRecombinant adeno-associated virus vector (rAAV) is an effective and safe gene-delivery tool. However, its application in solid-organ transplantation has not been addressed. The present study is designed to introduce human cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin G (hCTLA4Ig) by rAAV (rAAV-hCTLA4Ig) into rat liver grafts to analyze the effects of virus titer, exposure time, and route of administration on transgene expression and possible side effects caused by the gene-delivery approach. Different rAAV-hCTLA4Ig titers were introduced into liver grafts through back-table portal vein perfusion and preserved for a certain time. rAAV-hCTLA4Ig also was administered by intravenous and intramuscular injection. Transgene expression in grafts and plasma was detected by immunohistochemistry and enzyme-linked immunosorbent assay. Intragraft cytokine level was detected by reverse-transcriptase polymerase chain reaction. Anti-hCTLA4Ig antibodies in plasma were detected by flow cytometry. A higher virus titer (1 × 1012 viral genomes/animal) introduced through back-table portal vein perfusion and a longer preservation time (3 hours) achieved a greater level of transgene expression until day 180. Back-table portal vein perfusion induced a greater level of hCTLA4 expression in plasma than intramuscular or intravenous injection. Increased interleukin-2 and interferon-γ messenger RNA levels were detected in grafts with rAAV-hCTLA4Ig gene transfer compared with those without virus delivery, but the response was minor. Such a cellular immune response could be suppressed by low-dose FK506 administration during the first 3 postoperative days. Anti-hCTLA4Ig antibodies could be detected in long-term surviving animals, but the extent of humoral response was not severe. This study shows that rAAV can be an effective and safe vector for gene delivery in liver transplantation.
Persistent Identifierhttp://hdl.handle.net/10722/83274
ISSN
2015 Impact Factor: 3.951
2015 SCImago Journal Rankings: 1.763
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYang, ZFen_HK
dc.contributor.authorWu, XBen_HK
dc.contributor.authorTsui, TYen_HK
dc.contributor.authorHou, YDen_HK
dc.contributor.authorLuk, JMen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-06T08:39:04Z-
dc.date.available2010-09-06T08:39:04Z-
dc.date.issued2003en_HK
dc.identifier.citationLiver Transplantation, 2003, v. 9 n. 4, p. 411-420en_HK
dc.identifier.issn1527-6465en_HK
dc.identifier.urihttp://hdl.handle.net/10722/83274-
dc.description.abstractRecombinant adeno-associated virus vector (rAAV) is an effective and safe gene-delivery tool. However, its application in solid-organ transplantation has not been addressed. The present study is designed to introduce human cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin G (hCTLA4Ig) by rAAV (rAAV-hCTLA4Ig) into rat liver grafts to analyze the effects of virus titer, exposure time, and route of administration on transgene expression and possible side effects caused by the gene-delivery approach. Different rAAV-hCTLA4Ig titers were introduced into liver grafts through back-table portal vein perfusion and preserved for a certain time. rAAV-hCTLA4Ig also was administered by intravenous and intramuscular injection. Transgene expression in grafts and plasma was detected by immunohistochemistry and enzyme-linked immunosorbent assay. Intragraft cytokine level was detected by reverse-transcriptase polymerase chain reaction. Anti-hCTLA4Ig antibodies in plasma were detected by flow cytometry. A higher virus titer (1 × 1012 viral genomes/animal) introduced through back-table portal vein perfusion and a longer preservation time (3 hours) achieved a greater level of transgene expression until day 180. Back-table portal vein perfusion induced a greater level of hCTLA4 expression in plasma than intramuscular or intravenous injection. Increased interleukin-2 and interferon-γ messenger RNA levels were detected in grafts with rAAV-hCTLA4Ig gene transfer compared with those without virus delivery, but the response was minor. Such a cellular immune response could be suppressed by low-dose FK506 administration during the first 3 postoperative days. Anti-hCTLA4Ig antibodies could be detected in long-term surviving animals, but the extent of humoral response was not severe. This study shows that rAAV can be an effective and safe vector for gene delivery in liver transplantation.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jtoc/106570021en_HK
dc.relation.ispartofLiver Transplantationen_HK
dc.rightsLiver Transplantation. Copyright © John Wiley & Sons, Inc.en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAntibody Formationen_HK
dc.subject.meshAntigens, CDen_HK
dc.subject.meshAntigens, Differentiation - genetics - immunologyen_HK
dc.subject.meshCTLA-4 Antigenen_HK
dc.subject.meshDependovirus - geneticsen_HK
dc.subject.meshGene Expressionen_HK
dc.subject.meshGene Transfer Techniquesen_HK
dc.subject.meshGenetic Vectors - standardsen_HK
dc.subject.meshGraft Survivalen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunity, Cellularen_HK
dc.subject.meshLiver - pathologyen_HK
dc.subject.meshLiver Transplantationen_HK
dc.subject.meshMaleen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Inbred Lewen_HK
dc.subject.meshRecombination, Geneticen_HK
dc.titleRecombinant adeno-associated virus vector: Is it ideal for gene delivery in liver transplantation?en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1527-6465&volume=9&issue=4&spage=411&epage=420&date=2003&atitle=Recombinant+adeno-associated+virus+vector:+is+it+ideal+for+gene+delivery+in+liver+transplantation?en_HK
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityLuk, JM=rp00349en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1053/jlts.2003.50058en_HK
dc.identifier.pmid12682895-
dc.identifier.scopuseid_2-s2.0-0344950999en_HK
dc.identifier.hkuros82797en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0344950999&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume9en_HK
dc.identifier.issue4en_HK
dc.identifier.spage411en_HK
dc.identifier.epage420en_HK
dc.identifier.isiWOS:000182009300015-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYang, ZF=14018809600en_HK
dc.identifier.scopusauthoridWu, XB=7408231534en_HK
dc.identifier.scopusauthoridTsui, TY=7006622455en_HK
dc.identifier.scopusauthoridHou, YD=7402198565en_HK
dc.identifier.scopusauthoridLuk, JM=7006777791en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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