Engineering Tissue-Specific Expression of a Recombinant Adenovirus: Selective Transgene Transcription in the Pancreas Using the Amylase Promoter
Recombinant adenovirus accomplishes highly efficient gene transferin vivo.Adenoviral vectors would be more attractive vehicles for gene therapy if transgene expression was inducible and restricted to the target tissue. In these studies, we hypothesized that selective transgene expression of a recomb...
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Veröffentlicht in: | The Journal of surgical research 1997-10, Vol.72 (2), p.155-161 |
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creator | Dematteo, R.P. McClane, S.J. Fisher, K. Yeh, H. Chu, G. Burke, C. Raper, S.E. |
description | Recombinant adenovirus accomplishes highly efficient gene transferin vivo.Adenoviral vectors would be more attractive vehicles for gene therapy if transgene expression was inducible and restricted to the target tissue. In these studies, we hypothesized that selective transgene expression of a recombinant adenovirus could be accomplished by using a tissue-specific promoter of transcription. A replication-defective adenoviral vector was engineered to express thelacZmarker gene under control of the murine pancreatic amylase promoter. Expression of this vector occurred exclusively in the pancreas in neonatal and adult mice, while a similar vector with a constitutive promoter accomplished transgene expression in several organs. Within the adenoviral construct, the amylase promoter retained its ability to be induced by dexamethasone and insulin. This model will serve as a paradigm for selective and inducible adenoviral transgene expression. |
doi_str_mv | 10.1006/jsre.1997.5096 |
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In these studies, we hypothesized that selective transgene expression of a recombinant adenovirus could be accomplished by using a tissue-specific promoter of transcription. A replication-defective adenoviral vector was engineered to express thelacZmarker gene under control of the murine pancreatic amylase promoter. Expression of this vector occurred exclusively in the pancreas in neonatal and adult mice, while a similar vector with a constitutive promoter accomplished transgene expression in several organs. Within the adenoviral construct, the amylase promoter retained its ability to be induced by dexamethasone and insulin. This model will serve as a paradigm for selective and inducible adenoviral transgene expression.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1006/jsre.1997.5096</identifier><identifier>PMID: 9356237</identifier><identifier>CODEN: JSGRA2</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adenoviridae - genetics ; Adenoviridae - ultrastructure ; Amylases - analysis ; Amylases - genetics ; Animals ; Base Sequence ; Biological and medical sciences ; Blotting, Southern ; Dexamethasone - pharmacology ; DNA - analysis ; DNA - chemistry ; DNA - genetics ; Gene Expression Regulation, Viral ; Genetic Therapy ; Genetic Vectors ; HeLa Cells ; Humans ; Insulin - pharmacology ; Lac Operon - genetics ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Miscellaneous ; Models, Genetic ; Pancreas - enzymology ; Pancreas - metabolism ; Pharmacology. Drug treatments ; Promoter Regions, Genetic - genetics ; Recombination, Genetic ; Transcription, Genetic - genetics</subject><ispartof>The Journal of surgical research, 1997-10, Vol.72 (2), p.155-161</ispartof><rights>1997 Academic Press</rights><rights>1998 INIST-CNRS</rights><rights>Copyright 1997 Academic Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-db8fc6eb9e322a0e8e4dab789885cde59b31f371d6f29ced7f4506eb53e2dede3</citedby><cites>FETCH-LOGICAL-c474t-db8fc6eb9e322a0e8e4dab789885cde59b31f371d6f29ced7f4506eb53e2dede3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/jsre.1997.5096$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2076490$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9356237$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dematteo, R.P.</creatorcontrib><creatorcontrib>McClane, S.J.</creatorcontrib><creatorcontrib>Fisher, K.</creatorcontrib><creatorcontrib>Yeh, H.</creatorcontrib><creatorcontrib>Chu, G.</creatorcontrib><creatorcontrib>Burke, C.</creatorcontrib><creatorcontrib>Raper, S.E.</creatorcontrib><title>Engineering Tissue-Specific Expression of a Recombinant Adenovirus: Selective Transgene Transcription in the Pancreas Using the Amylase Promoter</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>Recombinant adenovirus accomplishes highly efficient gene transferin vivo.Adenoviral vectors would be more attractive vehicles for gene therapy if transgene expression was inducible and restricted to the target tissue. In these studies, we hypothesized that selective transgene expression of a recombinant adenovirus could be accomplished by using a tissue-specific promoter of transcription. A replication-defective adenoviral vector was engineered to express thelacZmarker gene under control of the murine pancreatic amylase promoter. Expression of this vector occurred exclusively in the pancreas in neonatal and adult mice, while a similar vector with a constitutive promoter accomplished transgene expression in several organs. Within the adenoviral construct, the amylase promoter retained its ability to be induced by dexamethasone and insulin. This model will serve as a paradigm for selective and inducible adenoviral transgene expression.</description><subject>Adenoviridae - genetics</subject><subject>Adenoviridae - ultrastructure</subject><subject>Amylases - analysis</subject><subject>Amylases - genetics</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Blotting, Southern</subject><subject>Dexamethasone - pharmacology</subject><subject>DNA - analysis</subject><subject>DNA - chemistry</subject><subject>DNA - genetics</subject><subject>Gene Expression Regulation, Viral</subject><subject>Genetic Therapy</subject><subject>Genetic Vectors</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Insulin - pharmacology</subject><subject>Lac Operon - genetics</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Miscellaneous</subject><subject>Models, Genetic</subject><subject>Pancreas - enzymology</subject><subject>Pancreas - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Recombination, Genetic</subject><subject>Transcription, Genetic - genetics</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUtv1DAUhS0EKkPLlh2SF4hdpk6cxDG7UTU8pEqgdrq2HPtmcJXYwTcZ0X_Rn4yjibpj5cf57r32OYR8yNk2Z6y-fsQI21xKsa2YrF-RTc5klTW14K_JhrGiyMqGlW_JO8RHls5S8AtyIXlVF1xsyPPeH50HiM4f6cEhzpDdj2Bc5wzd_x0jILrgaeiopndgwtA6r_1EdxZ8OLk44xd6Dz2YyZ2AHqL2eAS_7kx047SUO0-n30B_aW8iaKQPuMxbrnbDU68xSTEMYYJ4Rd50ukd4v66X5OHr_nDzPbv9-e3Hze42M6Uop8y2TWdqaCXwotAMGiitbkUjm6YyFirZ8rzjIrd1V0gDVnRlxRJfcSgsWOCX5PO57xjDnxlwUoNDA32vPYQZlZC8ERXnCdyeQRMDJrM7NUY36PikcqaWCNQSgVoiUEsEqeDj2nluB7Av-Op50j-tukaj-y4ZZRy-YAUTdSlZwpozBsmFk4Oo0Djw6S8uJreVDe5_L_gH04emsg</recordid><startdate>19971001</startdate><enddate>19971001</enddate><creator>Dematteo, R.P.</creator><creator>McClane, S.J.</creator><creator>Fisher, K.</creator><creator>Yeh, H.</creator><creator>Chu, G.</creator><creator>Burke, C.</creator><creator>Raper, S.E.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19971001</creationdate><title>Engineering Tissue-Specific Expression of a Recombinant Adenovirus: Selective Transgene Transcription in the Pancreas Using the Amylase Promoter</title><author>Dematteo, R.P. ; McClane, S.J. ; Fisher, K. ; Yeh, H. ; Chu, G. ; Burke, C. ; Raper, S.E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-db8fc6eb9e322a0e8e4dab789885cde59b31f371d6f29ced7f4506eb53e2dede3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Adenoviridae - genetics</topic><topic>Adenoviridae - ultrastructure</topic><topic>Amylases - analysis</topic><topic>Amylases - genetics</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Blotting, Southern</topic><topic>Dexamethasone - pharmacology</topic><topic>DNA - analysis</topic><topic>DNA - chemistry</topic><topic>DNA - genetics</topic><topic>Gene Expression Regulation, Viral</topic><topic>Genetic Therapy</topic><topic>Genetic Vectors</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Insulin - pharmacology</topic><topic>Lac Operon - genetics</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Miscellaneous</topic><topic>Models, Genetic</topic><topic>Pancreas - enzymology</topic><topic>Pancreas - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Recombination, Genetic</topic><topic>Transcription, Genetic - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dematteo, R.P.</creatorcontrib><creatorcontrib>McClane, S.J.</creatorcontrib><creatorcontrib>Fisher, K.</creatorcontrib><creatorcontrib>Yeh, H.</creatorcontrib><creatorcontrib>Chu, G.</creatorcontrib><creatorcontrib>Burke, C.</creatorcontrib><creatorcontrib>Raper, S.E.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dematteo, R.P.</au><au>McClane, S.J.</au><au>Fisher, K.</au><au>Yeh, H.</au><au>Chu, G.</au><au>Burke, C.</au><au>Raper, S.E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Engineering Tissue-Specific Expression of a Recombinant Adenovirus: Selective Transgene Transcription in the Pancreas Using the Amylase Promoter</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>1997-10-01</date><risdate>1997</risdate><volume>72</volume><issue>2</issue><spage>155</spage><epage>161</epage><pages>155-161</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><coden>JSGRA2</coden><abstract>Recombinant adenovirus accomplishes highly efficient gene transferin vivo.Adenoviral vectors would be more attractive vehicles for gene therapy if transgene expression was inducible and restricted to the target tissue. In these studies, we hypothesized that selective transgene expression of a recombinant adenovirus could be accomplished by using a tissue-specific promoter of transcription. A replication-defective adenoviral vector was engineered to express thelacZmarker gene under control of the murine pancreatic amylase promoter. Expression of this vector occurred exclusively in the pancreas in neonatal and adult mice, while a similar vector with a constitutive promoter accomplished transgene expression in several organs. Within the adenoviral construct, the amylase promoter retained its ability to be induced by dexamethasone and insulin. This model will serve as a paradigm for selective and inducible adenoviral transgene expression.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>9356237</pmid><doi>10.1006/jsre.1997.5096</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenoviridae - genetics Adenoviridae - ultrastructure Amylases - analysis Amylases - genetics Animals Base Sequence Biological and medical sciences Blotting, Southern Dexamethasone - pharmacology DNA - analysis DNA - chemistry DNA - genetics Gene Expression Regulation, Viral Genetic Therapy Genetic Vectors HeLa Cells Humans Insulin - pharmacology Lac Operon - genetics Medical sciences Mice Mice, Inbred C57BL Miscellaneous Models, Genetic Pancreas - enzymology Pancreas - metabolism Pharmacology. Drug treatments Promoter Regions, Genetic - genetics Recombination, Genetic Transcription, Genetic - genetics |
title | Engineering Tissue-Specific Expression of a Recombinant Adenovirus: Selective Transgene Transcription in the Pancreas Using the Amylase Promoter |
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