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Article: Development of recombinant adeno-associated virus and adenovirus cocktail system for efficient hTERTC27 polypeptide-mediated cancer gene therapy

TitleDevelopment of recombinant adeno-associated virus and adenovirus cocktail system for efficient hTERTC27 polypeptide-mediated cancer gene therapy
Authors
KeywordsAdeno-associated virus
Adenovirus
Glioblastoma
hTERTC27
Issue Date2008
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cgt
Citation
Cancer Gene Therapy, 2008, v. 15 n. 11, p. 723-732 How to Cite?
AbstractThe low in vivo transduction efficiency of recombinant adeno-associated virus (rAAV) and the undesirably strong immunogenicity of adenovirus (rAdv) have limited their clinical utilization in cancer gene therapy. We have previously demonstrated that intratumoral injection of rAAV expressing a C-terminal polypeptide of human telomerase reverse transcriptase (rAAV-hTERTC27) effectively inhibits the growth of glioblastoma xenografts in nude mice. To further improve its efficacy, we combined rAAV-hTERTC27 with rAdv and investigated the efficiency of the cocktail vectors in vivo. At a nontherapeutic dose (1 × 10 8 plaque-forming units (PFUs)), rAdv-null and rAdv-hTERTC27 were equipotent in enhancing the therapeutic efficacy of rAAV-hTERTC27 (1.5 × 10 11 v.g.), and complete tumor regression was achieved in 25% of the treated animals. Importantly, the combination of rAAV-hTERTC27 and a therapeutic dose (2.5 × 10 9 PFU) of rAdv-hTERTC27 significantly augmented the therapeutic effects and led to a 38% complete tumor regression rate. In vivo optical imaging also showed that rAAV-luc/rAdv-luc cocktail vectors could synergistically enhance the early transient and latent sustained expression of luciferase, as compared to rAdv-luc and rAAV-luc alone. These findings suggest that the combination of rAAV-hTERTC27 and a therapeutic dose of rAdv-hTERTC27 is potentially a promising treatment for glioblastoma, and the rAAV/rAdv cocktail vector system warrants further development for cancer gene therapy. © 2008 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/58432
ISSN
2015 Impact Factor: 2.532
2015 SCImago Journal Rankings: 1.020
ISI Accession Number ID
Funding AgencyGrant Number
Innovation and Technology FundITS/105/02
Hong Kong Research Grant Council (CUHK)7422/03M
Guangzhou Metropolitan Fund2005Z1-E0131
Funding Information:

The work was supported by Innovation and Technology Fund (ITS/105/02 to MCL) and grants from the Hong Kong Research Grant Council (CUHK 7422/03M to HFK) and Guangzhou Metropolitan Fund (2005Z1-E0131).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorGao, Yen_HK
dc.contributor.authorNg, SSMen_HK
dc.contributor.authorChau, DHWen_HK
dc.contributor.authorYao, Hen_HK
dc.contributor.authorYang, Cen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorHuang, PTen_HK
dc.contributor.authorHuang, Cen_HK
dc.contributor.authorHuang, JJen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorLin, MCen_HK
dc.date.accessioned2010-05-31T03:30:12Z-
dc.date.available2010-05-31T03:30:12Z-
dc.date.issued2008en_HK
dc.identifier.citationCancer Gene Therapy, 2008, v. 15 n. 11, p. 723-732en_HK
dc.identifier.issn0929-1903en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58432-
dc.description.abstractThe low in vivo transduction efficiency of recombinant adeno-associated virus (rAAV) and the undesirably strong immunogenicity of adenovirus (rAdv) have limited their clinical utilization in cancer gene therapy. We have previously demonstrated that intratumoral injection of rAAV expressing a C-terminal polypeptide of human telomerase reverse transcriptase (rAAV-hTERTC27) effectively inhibits the growth of glioblastoma xenografts in nude mice. To further improve its efficacy, we combined rAAV-hTERTC27 with rAdv and investigated the efficiency of the cocktail vectors in vivo. At a nontherapeutic dose (1 × 10 8 plaque-forming units (PFUs)), rAdv-null and rAdv-hTERTC27 were equipotent in enhancing the therapeutic efficacy of rAAV-hTERTC27 (1.5 × 10 11 v.g.), and complete tumor regression was achieved in 25% of the treated animals. Importantly, the combination of rAAV-hTERTC27 and a therapeutic dose (2.5 × 10 9 PFU) of rAdv-hTERTC27 significantly augmented the therapeutic effects and led to a 38% complete tumor regression rate. In vivo optical imaging also showed that rAAV-luc/rAdv-luc cocktail vectors could synergistically enhance the early transient and latent sustained expression of luciferase, as compared to rAdv-luc and rAAV-luc alone. These findings suggest that the combination of rAAV-hTERTC27 and a therapeutic dose of rAdv-hTERTC27 is potentially a promising treatment for glioblastoma, and the rAAV/rAdv cocktail vector system warrants further development for cancer gene therapy. © 2008 Nature Publishing Group All rights reserved.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cgten_HK
dc.relation.ispartofCancer Gene Therapyen_HK
dc.subjectAdeno-associated virusen_HK
dc.subjectAdenovirusen_HK
dc.subjectGlioblastomaen_HK
dc.subjecthTERTC27en_HK
dc.titleDevelopment of recombinant adeno-associated virus and adenovirus cocktail system for efficient hTERTC27 polypeptide-mediated cancer gene therapyen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0929-1903&volume=15&spage=723&epage=732&date=2008&atitle=Development+of+Recombinant+Adeno-associated+Virus+and+Adenovirus+Cocktail+System+for+Efficient+hTERTC27+Polypeptide-mediated+Cancer+Gene+Therapy.en_HK
dc.identifier.emailNg, SSM: ssmng@hku.hken_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.emailLin, MC: mcllin@hkucc.hku.hken_HK
dc.identifier.authorityNg, SSM=rp00767en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/cgt.2008.33en_HK
dc.identifier.pmid18535618-
dc.identifier.scopuseid_2-s2.0-53549088873en_HK
dc.identifier.hkuros154174en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-53549088873&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume15en_HK
dc.identifier.issue11en_HK
dc.identifier.spage723en_HK
dc.identifier.epage732en_HK
dc.identifier.isiWOS:000259826900004-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectCancer gene therapy using a novel anti-cancer polypeptide hTERTC27 delivered by a novel AAV and Adenovirus Cocktail vector system-
dc.identifier.scopusauthoridGao, Y=54792979500en_HK
dc.identifier.scopusauthoridNg, SSM=7403358718en_HK
dc.identifier.scopusauthoridChau, DHW=16315084100en_HK
dc.identifier.scopusauthoridYao, H=13104506400en_HK
dc.identifier.scopusauthoridYang, C=7407028637en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridHuang, PT=7403658582en_HK
dc.identifier.scopusauthoridHuang, C=7406879416en_HK
dc.identifier.scopusauthoridHuang, JJ=7407194640en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK
dc.identifier.citeulike2871482-

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