Strain-based Genetic Differences Regulate the Efficiency of Systemic Gene Delivery as Well as Expression
We have characterized the impact of strain-based genetic differences on the efficiency of the intravenous cationic liposome·DNA complex (CLDC)-based gene transfer and expression in mice. We also investigated what steps in the gene delivery and expression pathway appeared responsible for these strai...
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| Veröffentlicht in: | The Journal of biological chemistry 2002-02, Vol.277 (7), p.4966-4972 |
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| container_title | The Journal of biological chemistry |
| container_volume | 277 |
| creator | Liu, Yong Liggitt, H Denny Dow, Steven Handumrongkul, Chakkrapong Heath, Timothy D Debs, Robert J |
| description | We have characterized the impact of strain-based genetic differences on the efficiency of the intravenous cationic liposome·DNA
complex (CLDC)-based gene transfer and expression in mice. We also investigated what steps in the gene delivery and expression
pathway appeared responsible for these strain-related differences and whether such differences could be compensated for either
by agents that alter host pathways important in CLDC-mediated gene transfer and expression, or by changes in CLDC formulation.
We found that different mouse strains can exhibit different expression levels and/or differences in the amount of plasmid
DNA delivered to the organs where the DNA is expressed. Furthermore, drug pretreatment or reformulation of the CLDC could
improve DNA delivery and/or gene expression in a strain-specific fashion. We conclude that genetic factors critically modify
both the tissue deposition and the expression of genetic materials delivered by CLDC. Because manipulation of either the host
or the CLDC could at least partially compensate for these strain-related differences, such strategies may be required to effectively
use non-viral gene transfer approaches in genetically diverse populations. |
| doi_str_mv | 10.1074/jbc.M110285200 |
| format | Article |
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complex (CLDC)-based gene transfer and expression in mice. We also investigated what steps in the gene delivery and expression
pathway appeared responsible for these strain-related differences and whether such differences could be compensated for either
by agents that alter host pathways important in CLDC-mediated gene transfer and expression, or by changes in CLDC formulation.
We found that different mouse strains can exhibit different expression levels and/or differences in the amount of plasmid
DNA delivered to the organs where the DNA is expressed. Furthermore, drug pretreatment or reformulation of the CLDC could
improve DNA delivery and/or gene expression in a strain-specific fashion. We conclude that genetic factors critically modify
both the tissue deposition and the expression of genetic materials delivered by CLDC. Because manipulation of either the host
or the CLDC could at least partially compensate for these strain-related differences, such strategies may be required to effectively
use non-viral gene transfer approaches in genetically diverse populations.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M110285200</identifier><identifier>PMID: 11733533</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Animals ; Anti-Inflammatory Agents - pharmacology ; Blotting, Southern ; Dexamethasone - pharmacology ; Female ; Gene Transfer Techniques ; Genetic Therapy - methods ; Genetic Vectors ; Liposomes - chemistry ; Luciferases - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Phenotype ; Plasmids - metabolism ; Promoter Regions, Genetic ; Species Specificity ; Transfection ; Tumor Cells, Cultured</subject><ispartof>The Journal of biological chemistry, 2002-02, Vol.277 (7), p.4966-4972</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-e6bf9f9c0bf88246b35b3eea060fb2b64c338d54cb689597a16766d487fb91713</citedby><cites>FETCH-LOGICAL-c389t-e6bf9f9c0bf88246b35b3eea060fb2b64c338d54cb689597a16766d487fb91713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11733533$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Yong</creatorcontrib><creatorcontrib>Liggitt, H Denny</creatorcontrib><creatorcontrib>Dow, Steven</creatorcontrib><creatorcontrib>Handumrongkul, Chakkrapong</creatorcontrib><creatorcontrib>Heath, Timothy D</creatorcontrib><creatorcontrib>Debs, Robert J</creatorcontrib><title>Strain-based Genetic Differences Regulate the Efficiency of Systemic Gene Delivery as Well as Expression</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>We have characterized the impact of strain-based genetic differences on the efficiency of the intravenous cationic liposome·DNA
complex (CLDC)-based gene transfer and expression in mice. We also investigated what steps in the gene delivery and expression
pathway appeared responsible for these strain-related differences and whether such differences could be compensated for either
by agents that alter host pathways important in CLDC-mediated gene transfer and expression, or by changes in CLDC formulation.
We found that different mouse strains can exhibit different expression levels and/or differences in the amount of plasmid
DNA delivered to the organs where the DNA is expressed. Furthermore, drug pretreatment or reformulation of the CLDC could
improve DNA delivery and/or gene expression in a strain-specific fashion. We conclude that genetic factors critically modify
both the tissue deposition and the expression of genetic materials delivered by CLDC. Because manipulation of either the host
or the CLDC could at least partially compensate for these strain-related differences, such strategies may be required to effectively
use non-viral gene transfer approaches in genetically diverse populations.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Blotting, Southern</subject><subject>Dexamethasone - pharmacology</subject><subject>Female</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Liposomes - chemistry</subject><subject>Luciferases - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred ICR</subject><subject>Phenotype</subject><subject>Plasmids - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Species Specificity</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtvUzEQhS0EoqGwZYksFt3d1O_HErWhVCpCaotgZ9nOuNfVfQT7hpJ_z40SqcvO5izmO0ejOQh9pGRJiRbnjyEuv1NKmJGMkFdoQYnhDZf092u0IITRxjJpTtC7Wh_JPMLSt-iEUs255HyB2rup-Dw0wVdY4ysYYMoRX-aUoMAQoeJbeNh2fgI8tYBXKeWY58UOjwnf7eoE_czvffgSuvwXyg77in9B1-119W9ToNY8Du_Rm-S7Ch-Oeop-fl3dX3xrbn5cXV98uWkiN3ZqQIVkk40kJGOYUIHLwAE8USQFFpSInJu1FDEoY6XVniqt1FoYnYKlmvJTdHbI3ZTxzxbq5Ppc43yOH2DcVqepEFYz8iJIDZOaSjmDywMYy1hrgeQ2Jfe-7Bwlbl-Cm0twzyXMhk_H5G3oYf2MH78-A58PQJsf2qdcwIU8xhZ6x7R22gmrFP8PrBuN7A</recordid><startdate>20020215</startdate><enddate>20020215</enddate><creator>Liu, Yong</creator><creator>Liggitt, H Denny</creator><creator>Dow, Steven</creator><creator>Handumrongkul, Chakkrapong</creator><creator>Heath, Timothy D</creator><creator>Debs, Robert J</creator><general>American Society for Biochemistry and Molecular Biology</general><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20020215</creationdate><title>Strain-based Genetic Differences Regulate the Efficiency of Systemic Gene Delivery as Well as Expression</title><author>Liu, Yong ; Liggitt, H Denny ; Dow, Steven ; Handumrongkul, Chakkrapong ; Heath, Timothy D ; Debs, Robert J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-e6bf9f9c0bf88246b35b3eea060fb2b64c338d54cb689597a16766d487fb91713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Blotting, Southern</topic><topic>Dexamethasone - pharmacology</topic><topic>Female</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>Liposomes - chemistry</topic><topic>Luciferases - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred ICR</topic><topic>Phenotype</topic><topic>Plasmids - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Species Specificity</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Yong</creatorcontrib><creatorcontrib>Liggitt, H Denny</creatorcontrib><creatorcontrib>Dow, Steven</creatorcontrib><creatorcontrib>Handumrongkul, Chakkrapong</creatorcontrib><creatorcontrib>Heath, Timothy D</creatorcontrib><creatorcontrib>Debs, Robert J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Yong</au><au>Liggitt, H Denny</au><au>Dow, Steven</au><au>Handumrongkul, Chakkrapong</au><au>Heath, Timothy D</au><au>Debs, Robert J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Strain-based Genetic Differences Regulate the Efficiency of Systemic Gene Delivery as Well as Expression</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2002-02-15</date><risdate>2002</risdate><volume>277</volume><issue>7</issue><spage>4966</spage><epage>4972</epage><pages>4966-4972</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>We have characterized the impact of strain-based genetic differences on the efficiency of the intravenous cationic liposome·DNA
complex (CLDC)-based gene transfer and expression in mice. We also investigated what steps in the gene delivery and expression
pathway appeared responsible for these strain-related differences and whether such differences could be compensated for either
by agents that alter host pathways important in CLDC-mediated gene transfer and expression, or by changes in CLDC formulation.
We found that different mouse strains can exhibit different expression levels and/or differences in the amount of plasmid
DNA delivered to the organs where the DNA is expressed. Furthermore, drug pretreatment or reformulation of the CLDC could
improve DNA delivery and/or gene expression in a strain-specific fashion. We conclude that genetic factors critically modify
both the tissue deposition and the expression of genetic materials delivered by CLDC. Because manipulation of either the host
or the CLDC could at least partially compensate for these strain-related differences, such strategies may be required to effectively
use non-viral gene transfer approaches in genetically diverse populations.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>11733533</pmid><doi>10.1074/jbc.M110285200</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 2002-02, Vol.277 (7), p.4966-4972 |
| issn | 0021-9258 1083-351X |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Anti-Inflammatory Agents - pharmacology Blotting, Southern Dexamethasone - pharmacology Female Gene Transfer Techniques Genetic Therapy - methods Genetic Vectors Liposomes - chemistry Luciferases - metabolism Mice Mice, Inbred C57BL Mice, Inbred ICR Phenotype Plasmids - metabolism Promoter Regions, Genetic Species Specificity Transfection Tumor Cells, Cultured |
| title | Strain-based Genetic Differences Regulate the Efficiency of Systemic Gene Delivery as Well as Expression |
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