A gene delivery system containing nuclear localization signal: Increased nucleus import and transfection efficiency with the assistance of RanGAP1
[Display omitted] In the present report, a degradable gene delivery system (PAMS/DNA/10NLS) containing nucleus location signal peptide (NLS) was prepared. The agarose gel electrophoresis, particle size and zeta potential of PAMS/DNA/10NLS were similar to those of PAMS/DNA, which proved that NLS did...
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| Veröffentlicht in: | Acta biomaterialia 2017-01, Vol.48, p.215-226 |
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| creator | Chen, Kang Guo, Lingling Zhang, Jiulong Chen, Qing Wang, Kuanglei Li, Chenxi Li, Weinan Qiao, Mingxi Zhao, Xiuli Hu, Haiyang Chen, Dawei |
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In the present report, a degradable gene delivery system (PAMS/DNA/10NLS) containing nucleus location signal peptide (NLS) was prepared. The agarose gel electrophoresis, particle size and zeta potential of PAMS/DNA/10NLS were similar to those of PAMS/DNA, which proved that NLS did not affect the interaction between PAMS and DNA. PAMS/DNA/10NLS exhibited marked extracellular and intracellular degradation under acidic conditions. The degradation was believed to allow NLS to come into contact with importins easily, which was able to mediate the nucleus import. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. Moreover, the transfection of PAMS/DNA/10NLS was less dependent on the breakdown of the nucleus envelope than PAMS/DNA. Considering that GTPase-activating protein 1 (RanGAP1) was able to activate the endogenous GTPase, which was necessary for NLS-mediated nucleus import, RanGAP1 overexpressed cells (RanGAP1 cells) were produced. This result showed that RanGAP1 cells had higher GTPase activities than normal cells. Both the nucleus import and transfection efficiency of PAMS/DNA/10NLS were markedly higher in RanGAP1 cells than that in normal cells. The in vivo transfection results also showed that the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice. These findings showed that PAMS/DNA/10NLS is a promising gene delivery system with the assistance of RanGAP1.
The present report describes the increased transfection efficiency of a degradable gene delivery system (PAMS/DNA/10NLS) containing nuclear location signal (NLS) with the assistance of GTPase-activating protein 1 (RanGAP1). The physicochemical properties of PAMS/DNA/10NLS were similar to those of PAMS/DNA. PAMS/DNA/10NLS exhibited great extracellular and intracellular degradations, which might allow NLS to contact with importins easily. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. The transfection of PAMS/DNA/10NLS had less dependence on the breakdown of nuclear envelope. Both the nuclear import and transfection efficiency of PAMS/DNA/10NLS were higher in RanGAP1 overexpressed cells than that in normal cells. Moreover, the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice. |
| doi_str_mv | 10.1016/j.actbio.2016.11.004 |
| format | Article |
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In the present report, a degradable gene delivery system (PAMS/DNA/10NLS) containing nucleus location signal peptide (NLS) was prepared. The agarose gel electrophoresis, particle size and zeta potential of PAMS/DNA/10NLS were similar to those of PAMS/DNA, which proved that NLS did not affect the interaction between PAMS and DNA. PAMS/DNA/10NLS exhibited marked extracellular and intracellular degradation under acidic conditions. The degradation was believed to allow NLS to come into contact with importins easily, which was able to mediate the nucleus import. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. Moreover, the transfection of PAMS/DNA/10NLS was less dependent on the breakdown of the nucleus envelope than PAMS/DNA. Considering that GTPase-activating protein 1 (RanGAP1) was able to activate the endogenous GTPase, which was necessary for NLS-mediated nucleus import, RanGAP1 overexpressed cells (RanGAP1 cells) were produced. This result showed that RanGAP1 cells had higher GTPase activities than normal cells. Both the nucleus import and transfection efficiency of PAMS/DNA/10NLS were markedly higher in RanGAP1 cells than that in normal cells. The in vivo transfection results also showed that the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice. These findings showed that PAMS/DNA/10NLS is a promising gene delivery system with the assistance of RanGAP1.
The present report describes the increased transfection efficiency of a degradable gene delivery system (PAMS/DNA/10NLS) containing nuclear location signal (NLS) with the assistance of GTPase-activating protein 1 (RanGAP1). The physicochemical properties of PAMS/DNA/10NLS were similar to those of PAMS/DNA. PAMS/DNA/10NLS exhibited great extracellular and intracellular degradations, which might allow NLS to contact with importins easily. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. The transfection of PAMS/DNA/10NLS had less dependence on the breakdown of nuclear envelope. Both the nuclear import and transfection efficiency of PAMS/DNA/10NLS were higher in RanGAP1 overexpressed cells than that in normal cells. Moreover, the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2016.11.004</identifier><identifier>PMID: 27816620</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Active Transport, Cell Nucleus ; Animals ; Breakdown ; Cell Line ; Cell Nucleus - metabolism ; Degradable gene delivery system ; Degradation ; Dendrimers - chemistry ; Deoxyribonucleic acid ; DNA ; DNA - metabolism ; Efficiency ; Female ; Gel electrophoresis ; Gene transfer ; GTPase-activating protein ; GTPase-Activating Proteins - metabolism ; Guanosine triphosphatases ; Imports ; Intracellular ; Localization ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nuclear Envelope - metabolism ; Nuclear Localization Signals - metabolism ; Nuclear transport ; Nuclei (cytology) ; Nucleus import ; Nucleus location signal ; Particle Size ; Physicochemical properties ; RanGAP1 ; Static Electricity ; Transfection ; Transfection - methods ; Zeta potential</subject><ispartof>Acta biomaterialia, 2017-01, Vol.48, p.215-226</ispartof><rights>2016 Acta Materialia Inc.</rights><rights>Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Jan 15, 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-7e6116ea8d11da0e6cc67fcea86adf7e4df4989cee06314c0f79127780c1eeca3</citedby><cites>FETCH-LOGICAL-c390t-7e6116ea8d11da0e6cc67fcea86adf7e4df4989cee06314c0f79127780c1eeca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.actbio.2016.11.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27816620$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Kang</creatorcontrib><creatorcontrib>Guo, Lingling</creatorcontrib><creatorcontrib>Zhang, Jiulong</creatorcontrib><creatorcontrib>Chen, Qing</creatorcontrib><creatorcontrib>Wang, Kuanglei</creatorcontrib><creatorcontrib>Li, Chenxi</creatorcontrib><creatorcontrib>Li, Weinan</creatorcontrib><creatorcontrib>Qiao, Mingxi</creatorcontrib><creatorcontrib>Zhao, Xiuli</creatorcontrib><creatorcontrib>Hu, Haiyang</creatorcontrib><creatorcontrib>Chen, Dawei</creatorcontrib><title>A gene delivery system containing nuclear localization signal: Increased nucleus import and transfection efficiency with the assistance of RanGAP1</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted]
In the present report, a degradable gene delivery system (PAMS/DNA/10NLS) containing nucleus location signal peptide (NLS) was prepared. The agarose gel electrophoresis, particle size and zeta potential of PAMS/DNA/10NLS were similar to those of PAMS/DNA, which proved that NLS did not affect the interaction between PAMS and DNA. PAMS/DNA/10NLS exhibited marked extracellular and intracellular degradation under acidic conditions. The degradation was believed to allow NLS to come into contact with importins easily, which was able to mediate the nucleus import. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. Moreover, the transfection of PAMS/DNA/10NLS was less dependent on the breakdown of the nucleus envelope than PAMS/DNA. Considering that GTPase-activating protein 1 (RanGAP1) was able to activate the endogenous GTPase, which was necessary for NLS-mediated nucleus import, RanGAP1 overexpressed cells (RanGAP1 cells) were produced. This result showed that RanGAP1 cells had higher GTPase activities than normal cells. Both the nucleus import and transfection efficiency of PAMS/DNA/10NLS were markedly higher in RanGAP1 cells than that in normal cells. The in vivo transfection results also showed that the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice. These findings showed that PAMS/DNA/10NLS is a promising gene delivery system with the assistance of RanGAP1.
The present report describes the increased transfection efficiency of a degradable gene delivery system (PAMS/DNA/10NLS) containing nuclear location signal (NLS) with the assistance of GTPase-activating protein 1 (RanGAP1). The physicochemical properties of PAMS/DNA/10NLS were similar to those of PAMS/DNA. PAMS/DNA/10NLS exhibited great extracellular and intracellular degradations, which might allow NLS to contact with importins easily. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. The transfection of PAMS/DNA/10NLS had less dependence on the breakdown of nuclear envelope. Both the nuclear import and transfection efficiency of PAMS/DNA/10NLS were higher in RanGAP1 overexpressed cells than that in normal cells. Moreover, the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice.</description><subject>Active Transport, Cell Nucleus</subject><subject>Animals</subject><subject>Breakdown</subject><subject>Cell Line</subject><subject>Cell Nucleus - metabolism</subject><subject>Degradable gene delivery system</subject><subject>Degradation</subject><subject>Dendrimers - chemistry</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - metabolism</subject><subject>Efficiency</subject><subject>Female</subject><subject>Gel electrophoresis</subject><subject>Gene transfer</subject><subject>GTPase-activating protein</subject><subject>GTPase-Activating Proteins - metabolism</subject><subject>Guanosine triphosphatases</subject><subject>Imports</subject><subject>Intracellular</subject><subject>Localization</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Nuclear Envelope - metabolism</subject><subject>Nuclear Localization Signals - metabolism</subject><subject>Nuclear transport</subject><subject>Nuclei (cytology)</subject><subject>Nucleus import</subject><subject>Nucleus location signal</subject><subject>Particle Size</subject><subject>Physicochemical properties</subject><subject>RanGAP1</subject><subject>Static Electricity</subject><subject>Transfection</subject><subject>Transfection - methods</subject><subject>Zeta potential</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1rFTEUhoMotlb_gUjAjZsZc2amScaFcClaCwVFdB3S5OQ2l5nkmmRarj_DX2zaqS5cuMoHz3sOvA8hL4G1wIC_3bXalCsf266-WoCWseEROQYpZCNOuXxc72LoGsE4HJFnOe8Y6yV08ik56oQEzjt2TH5t6BYDUouTv8F0oPmQC87UxFC0Dz5saVjMhDrRKRo9-Z-6-Bho9tugp3f0IpiEOqNdsSVTP-9jKlQHS0vSITs09wl0zhuPwRzorS_XtFwj1Tn7XHQwSKOjX3U433yB5-SJ01PGFw_nCfn-8cO3s0_N5efzi7PNZWP6kZVGIAfgqKUFsJohN4YLZ-oH19YJHKwbRjkaRMZ7GAxzYoROCMkMIBrdn5A369x9ij8WzEXNPhucJh0wLlmB7AXrTqUcK_r6H3QXl1QLqNQIHIZeDH2lhpUyKeac0Kl98rNOBwVM3TlTO7U6U3fOFICqzmrs1cPw5WpG-zf0R1IF3q8A1jZuPCaV74tE61MtV9no_7_hNzwwrK4</recordid><startdate>20170115</startdate><enddate>20170115</enddate><creator>Chen, Kang</creator><creator>Guo, Lingling</creator><creator>Zhang, Jiulong</creator><creator>Chen, Qing</creator><creator>Wang, Kuanglei</creator><creator>Li, Chenxi</creator><creator>Li, Weinan</creator><creator>Qiao, Mingxi</creator><creator>Zhao, Xiuli</creator><creator>Hu, Haiyang</creator><creator>Chen, Dawei</creator><general>Elsevier Ltd</general><general>Elsevier BV</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20170115</creationdate><title>A gene delivery system containing nuclear localization signal: Increased nucleus import and transfection efficiency with the assistance of RanGAP1</title><author>Chen, Kang ; Guo, Lingling ; Zhang, Jiulong ; Chen, Qing ; Wang, Kuanglei ; Li, Chenxi ; Li, Weinan ; Qiao, Mingxi ; Zhao, Xiuli ; Hu, Haiyang ; Chen, Dawei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-7e6116ea8d11da0e6cc67fcea86adf7e4df4989cee06314c0f79127780c1eeca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Active Transport, Cell Nucleus</topic><topic>Animals</topic><topic>Breakdown</topic><topic>Cell Line</topic><topic>Cell Nucleus - metabolism</topic><topic>Degradable gene delivery system</topic><topic>Degradation</topic><topic>Dendrimers - chemistry</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - metabolism</topic><topic>Efficiency</topic><topic>Female</topic><topic>Gel electrophoresis</topic><topic>Gene transfer</topic><topic>GTPase-activating protein</topic><topic>GTPase-Activating Proteins - metabolism</topic><topic>Guanosine triphosphatases</topic><topic>Imports</topic><topic>Intracellular</topic><topic>Localization</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Nuclear Envelope - metabolism</topic><topic>Nuclear Localization Signals - metabolism</topic><topic>Nuclear transport</topic><topic>Nuclei (cytology)</topic><topic>Nucleus import</topic><topic>Nucleus location signal</topic><topic>Particle Size</topic><topic>Physicochemical properties</topic><topic>RanGAP1</topic><topic>Static Electricity</topic><topic>Transfection</topic><topic>Transfection - methods</topic><topic>Zeta potential</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Kang</creatorcontrib><creatorcontrib>Guo, Lingling</creatorcontrib><creatorcontrib>Zhang, Jiulong</creatorcontrib><creatorcontrib>Chen, Qing</creatorcontrib><creatorcontrib>Wang, Kuanglei</creatorcontrib><creatorcontrib>Li, Chenxi</creatorcontrib><creatorcontrib>Li, Weinan</creatorcontrib><creatorcontrib>Qiao, Mingxi</creatorcontrib><creatorcontrib>Zhao, Xiuli</creatorcontrib><creatorcontrib>Hu, Haiyang</creatorcontrib><creatorcontrib>Chen, Dawei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Kang</au><au>Guo, Lingling</au><au>Zhang, Jiulong</au><au>Chen, Qing</au><au>Wang, Kuanglei</au><au>Li, Chenxi</au><au>Li, Weinan</au><au>Qiao, Mingxi</au><au>Zhao, Xiuli</au><au>Hu, Haiyang</au><au>Chen, Dawei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A gene delivery system containing nuclear localization signal: Increased nucleus import and transfection efficiency with the assistance of RanGAP1</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2017-01-15</date><risdate>2017</risdate><volume>48</volume><spage>215</spage><epage>226</epage><pages>215-226</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>[Display omitted]
In the present report, a degradable gene delivery system (PAMS/DNA/10NLS) containing nucleus location signal peptide (NLS) was prepared. The agarose gel electrophoresis, particle size and zeta potential of PAMS/DNA/10NLS were similar to those of PAMS/DNA, which proved that NLS did not affect the interaction between PAMS and DNA. PAMS/DNA/10NLS exhibited marked extracellular and intracellular degradation under acidic conditions. The degradation was believed to allow NLS to come into contact with importins easily, which was able to mediate the nucleus import. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. Moreover, the transfection of PAMS/DNA/10NLS was less dependent on the breakdown of the nucleus envelope than PAMS/DNA. Considering that GTPase-activating protein 1 (RanGAP1) was able to activate the endogenous GTPase, which was necessary for NLS-mediated nucleus import, RanGAP1 overexpressed cells (RanGAP1 cells) were produced. This result showed that RanGAP1 cells had higher GTPase activities than normal cells. Both the nucleus import and transfection efficiency of PAMS/DNA/10NLS were markedly higher in RanGAP1 cells than that in normal cells. The in vivo transfection results also showed that the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice. These findings showed that PAMS/DNA/10NLS is a promising gene delivery system with the assistance of RanGAP1.
The present report describes the increased transfection efficiency of a degradable gene delivery system (PAMS/DNA/10NLS) containing nuclear location signal (NLS) with the assistance of GTPase-activating protein 1 (RanGAP1). The physicochemical properties of PAMS/DNA/10NLS were similar to those of PAMS/DNA. PAMS/DNA/10NLS exhibited great extracellular and intracellular degradations, which might allow NLS to contact with importins easily. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. The transfection of PAMS/DNA/10NLS had less dependence on the breakdown of nuclear envelope. Both the nuclear import and transfection efficiency of PAMS/DNA/10NLS were higher in RanGAP1 overexpressed cells than that in normal cells. Moreover, the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27816620</pmid><doi>10.1016/j.actbio.2016.11.004</doi><tpages>12</tpages></addata></record> |
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| ispartof | Acta biomaterialia, 2017-01, Vol.48, p.215-226 |
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| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Active Transport, Cell Nucleus Animals Breakdown Cell Line Cell Nucleus - metabolism Degradable gene delivery system Degradation Dendrimers - chemistry Deoxyribonucleic acid DNA DNA - metabolism Efficiency Female Gel electrophoresis Gene transfer GTPase-activating protein GTPase-Activating Proteins - metabolism Guanosine triphosphatases Imports Intracellular Localization Mice Mice, Inbred BALB C Mice, Nude Nuclear Envelope - metabolism Nuclear Localization Signals - metabolism Nuclear transport Nuclei (cytology) Nucleus import Nucleus location signal Particle Size Physicochemical properties RanGAP1 Static Electricity Transfection Transfection - methods Zeta potential |
| title | A gene delivery system containing nuclear localization signal: Increased nucleus import and transfection efficiency with the assistance of RanGAP1 |
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