537. Charge-Reversal Lipids for Gene Transfection
One of the critical steps limiting the efficiency of non-viral gene delivery is the intracellular release of DNA from the vector complex. The complex should be stable enough to prevent DNA degradation but also dissociate from the DNA once inside the cell for subsequent transcription. To facilitate t...
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| Veröffentlicht in: | Molecular therapy 2006-05, Vol.13 (S1), p.S206-S207 |
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| container_title | Molecular therapy |
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| creator | Grinstaff, Mark W. Hernandez Prata, Carla A. Meyers, Steven R. Barthelemy, Philippe Li, Yougen Luo, Dan McIntosh, Tom J. Lee, Stephen J. |
| description | One of the critical steps limiting the efficiency of non-viral gene delivery is the intracellular release of DNA from the vector complex. The complex should be stable enough to prevent DNA degradation but also dissociate from the DNA once inside the cell for subsequent transcription. To facilitate the escape of DNA from the DNA-lipid complex in the cell, and thus improve transfection efficiency, we have developed esterase sensitive cationic lipids. These lipids form a strong complex with DNA. Once in the endosome, esterases hydrolyze the terminal ester linkage of the lipid affecting a change in overall lipid charge from cationic to anionic. This charge-reversal transition releases the DNA from the lipids. These charge-reversal lipids (Fig. 1) were synthesized and characterized. The complexation and dissociation of the lipid to the DNA was monitored using an ethidium bromide displacement assay. The supramolecular lipid/DNA complexes were also characterized by dynamic light scattering, TEM and X-ray diffraction. Successful gene transfection was observed with this new class of lipids with CHO, K562, and HEK293 cells. |
| doi_str_mv | 10.1016/j.ymthe.2006.08.608 |
| format | Article |
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Charge-Reversal Lipids for Gene Transfection</title><source>Free E-Journal (出版社公開部分のみ）</source><source>ProQuest Central UK/Ireland</source><source>Alma/SFX Local Collection</source><creator>Grinstaff, Mark W. ; Hernandez Prata, Carla A. ; Meyers, Steven R. ; Barthelemy, Philippe ; Li, Yougen ; Luo, Dan ; McIntosh, Tom J. ; Lee, Stephen J.</creator><creatorcontrib>Grinstaff, Mark W. ; Hernandez Prata, Carla A. ; Meyers, Steven R. ; Barthelemy, Philippe ; Li, Yougen ; Luo, Dan ; McIntosh, Tom J. ; Lee, Stephen J.</creatorcontrib><description>One of the critical steps limiting the efficiency of non-viral gene delivery is the intracellular release of DNA from the vector complex. The complex should be stable enough to prevent DNA degradation but also dissociate from the DNA once inside the cell for subsequent transcription. To facilitate the escape of DNA from the DNA-lipid complex in the cell, and thus improve transfection efficiency, we have developed esterase sensitive cationic lipids. These lipids form a strong complex with DNA. Once in the endosome, esterases hydrolyze the terminal ester linkage of the lipid affecting a change in overall lipid charge from cationic to anionic. This charge-reversal transition releases the DNA from the lipids. These charge-reversal lipids (Fig. 1) were synthesized and characterized. The complexation and dissociation of the lipid to the DNA was monitored using an ethidium bromide displacement assay. The supramolecular lipid/DNA complexes were also characterized by dynamic light scattering, TEM and X-ray diffraction. 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Charge-Reversal Lipids for Gene Transfection</title><title>Molecular therapy</title><description>One of the critical steps limiting the efficiency of non-viral gene delivery is the intracellular release of DNA from the vector complex. The complex should be stable enough to prevent DNA degradation but also dissociate from the DNA once inside the cell for subsequent transcription. To facilitate the escape of DNA from the DNA-lipid complex in the cell, and thus improve transfection efficiency, we have developed esterase sensitive cationic lipids. These lipids form a strong complex with DNA. Once in the endosome, esterases hydrolyze the terminal ester linkage of the lipid affecting a change in overall lipid charge from cationic to anionic. This charge-reversal transition releases the DNA from the lipids. These charge-reversal lipids (Fig. 1) were synthesized and characterized. The complexation and dissociation of the lipid to the DNA was monitored using an ethidium bromide displacement assay. The supramolecular lipid/DNA complexes were also characterized by dynamic light scattering, TEM and X-ray diffraction. Successful gene transfection was observed with this new class of lipids with CHO, K562, and HEK293 cells.</description><subject>Cellulose</subject><subject>Efficiency</subject><subject>Engineering</subject><subject>Environmental engineering</subject><subject>Lipids</subject><subject>Microscopy</subject><subject>Protein expression</subject><subject>Reagents</subject><subject>Toxicity</subject><subject>Vectors (Biology)</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNo9kEFLw0AQhRdRsFZ_gQcDnhNnNpvN7lGKVqEgSD0vk3TXJjRJ3U2E_nvTRnqad3jfG_gYu0dIEFA-1cmh6bc24QAyAZVIUBdshhnPYgAuLs8Z5TW7CaEeE2ZazhhmaZ5Eiy35bxt_2l_rA-2iVbWvNiFynY-WtrXR2lMbnC37qmtv2ZWjXbB3_3fOvl5f1ou3ePWxfF88r-ISBaoYQZbjNgnhCl1YzTeFkIVCJ3heaEm6hDwlpwqUQhMpjsoRqFKnQJwLnc7Z47S7993PYENv6m7w7fjSYK55rlFqGFvp1Cp9F4K3zux91ZA_GARzdGNqc3Jjjm4MKDO6GamHiWqpH7w9M01_bMlcpX8W4mDl</recordid><startdate>20060501</startdate><enddate>20060501</enddate><creator>Grinstaff, Mark W.</creator><creator>Hernandez Prata, Carla A.</creator><creator>Meyers, Steven R.</creator><creator>Barthelemy, Philippe</creator><creator>Li, Yougen</creator><creator>Luo, Dan</creator><creator>McIntosh, Tom J.</creator><creator>Lee, Stephen J.</creator><general>Elsevier Limited</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20060501</creationdate><title>537. Charge-Reversal Lipids for Gene Transfection</title><author>Grinstaff, Mark W. ; Hernandez Prata, Carla A. ; Meyers, Steven R. ; Barthelemy, Philippe ; Li, Yougen ; Luo, Dan ; McIntosh, Tom J. ; Lee, Stephen J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1418-106c537a44fb9be92db46b81f427b96a9c073af8b1649aa8218fa08c930a22493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Cellulose</topic><topic>Efficiency</topic><topic>Engineering</topic><topic>Environmental engineering</topic><topic>Lipids</topic><topic>Microscopy</topic><topic>Protein expression</topic><topic>Reagents</topic><topic>Toxicity</topic><topic>Vectors (Biology)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grinstaff, Mark W.</creatorcontrib><creatorcontrib>Hernandez Prata, Carla A.</creatorcontrib><creatorcontrib>Meyers, Steven R.</creatorcontrib><creatorcontrib>Barthelemy, Philippe</creatorcontrib><creatorcontrib>Li, Yougen</creatorcontrib><creatorcontrib>Luo, Dan</creatorcontrib><creatorcontrib>McIntosh, Tom J.</creatorcontrib><creatorcontrib>Lee, Stephen J.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Biological Science Journals</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Molecular therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grinstaff, Mark W.</au><au>Hernandez Prata, Carla A.</au><au>Meyers, Steven R.</au><au>Barthelemy, Philippe</au><au>Li, Yougen</au><au>Luo, Dan</au><au>McIntosh, Tom J.</au><au>Lee, Stephen J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>537. Charge-Reversal Lipids for Gene Transfection</atitle><jtitle>Molecular therapy</jtitle><date>2006-05-01</date><risdate>2006</risdate><volume>13</volume><issue>S1</issue><spage>S206</spage><epage>S207</epage><pages>S206-S207</pages><issn>1525-0016</issn><eissn>1525-0024</eissn><abstract>One of the critical steps limiting the efficiency of non-viral gene delivery is the intracellular release of DNA from the vector complex. The complex should be stable enough to prevent DNA degradation but also dissociate from the DNA once inside the cell for subsequent transcription. To facilitate the escape of DNA from the DNA-lipid complex in the cell, and thus improve transfection efficiency, we have developed esterase sensitive cationic lipids. These lipids form a strong complex with DNA. Once in the endosome, esterases hydrolyze the terminal ester linkage of the lipid affecting a change in overall lipid charge from cationic to anionic. 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| subjects | Cellulose Efficiency Engineering Environmental engineering Lipids Microscopy Protein expression Reagents Toxicity Vectors (Biology) |
| title | 537. Charge-Reversal Lipids for Gene Transfection |
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