Stable polyplexes based on arginine-containing oligopeptides for in vivo gene delivery
In this study, we investigated to what extent the stability and transduction capacity of polyplexed DNA can be improved by optimizing the condensing peptide sequence. We have synthesized a small library of cationic peptides, at which the lysine/arginine ratio and the cation charge were varied. All p...
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| Veröffentlicht in: | Gene therapy 2004-03, Vol.11 (5), p.457-464 |
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| creator | VAN ROSSENBERG, S. M. W VAN KEULEN, A. C. I DRIJFHOUT, J.-W VASTO, S KOERTEN, H. K SPIES, F VAN'T NOORDENDE, J. M VAN BERKEL, T. H. J. C BIESSEN, E. A. L |
| description | In this study, we investigated to what extent the stability and transduction capacity of polyplexed DNA can be improved by optimizing the condensing peptide sequence. We have synthesized a small library of cationic peptides, at which the lysine/arginine ratio and the cation charge were varied. All peptides were able to compact DNA, at which polyplexes of short lysine-rich sequences were considerably larger than those of elongated or arginine-rich peptides (GM102 and GM202). In addition, the arginine-rich peptides GM102 and GM202 rendered the polyplexes resistant to plasma incubation or DNase I-mediated digestion. While all peptides were found to improve the transfection efficiency in HepG2 cells, only the GM102- and GM202-derived polyplexes could be specifically targeted to HepG2 cells by incorporation of a ligand-derivatized YKAK(8)WK peptide. We propose that GM102 and GM202 combine the advantage of small condensing peptides to give small-sized polyplexes with the superior stability of condensing polymers, which makes GM102 and GM202 excellent candidates for future in vivo gene therapy studies. |
| doi_str_mv | 10.1038/sj.gt.3302183 |
| format | Article |
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M. W ; VAN KEULEN, A. C. I ; DRIJFHOUT, J.-W ; VASTO, S ; KOERTEN, H. K ; SPIES, F ; VAN'T NOORDENDE, J. M ; VAN BERKEL, T. H. J. C ; BIESSEN, E. A. L</creator><creatorcontrib>VAN ROSSENBERG, S. M. W ; VAN KEULEN, A. C. I ; DRIJFHOUT, J.-W ; VASTO, S ; KOERTEN, H. K ; SPIES, F ; VAN'T NOORDENDE, J. M ; VAN BERKEL, T. H. J. C ; BIESSEN, E. A. L</creatorcontrib><description>In this study, we investigated to what extent the stability and transduction capacity of polyplexed DNA can be improved by optimizing the condensing peptide sequence. We have synthesized a small library of cationic peptides, at which the lysine/arginine ratio and the cation charge were varied. All peptides were able to compact DNA, at which polyplexes of short lysine-rich sequences were considerably larger than those of elongated or arginine-rich peptides (GM102 and GM202). In addition, the arginine-rich peptides GM102 and GM202 rendered the polyplexes resistant to plasma incubation or DNase I-mediated digestion. While all peptides were found to improve the transfection efficiency in HepG2 cells, only the GM102- and GM202-derived polyplexes could be specifically targeted to HepG2 cells by incorporation of a ligand-derivatized YKAK(8)WK peptide. We propose that GM102 and GM202 combine the advantage of small condensing peptides to give small-sized polyplexes with the superior stability of condensing polymers, which makes GM102 and GM202 excellent candidates for future in vivo gene therapy studies.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/sj.gt.3302183</identifier><identifier>PMID: 14973539</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Amino Acid Sequence ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Applied cell therapy and gene therapy ; Arginine ; Arginine - chemistry ; arginine-rich peptides ; Biological and medical sciences ; Biotechnology ; Cationic peptides ; Chemical Phenomena ; Chemistry, Physical ; Deoxyribonuclease ; Deoxyribonuclease I - chemistry ; Deoxyribonucleic acid ; DNA ; Drug Stability ; Fundamental and applied biological sciences. Psychology ; Gene Targeting - methods ; Gene therapy ; Gene transfer ; Gene Transfer Techniques ; Genetic Vectors - chemistry ; Genetic Vectors - pharmacokinetics ; Health. Pharmaceutical industry ; Humans ; Industrial applications and implications. Economical aspects ; Lysine ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Nucleotide sequence ; Oligopeptides ; Oligopeptides - chemistry ; Oligopeptides - genetics ; Oligopeptides - pharmacokinetics ; Peptide Fragments - chemistry ; Peptides ; polyplexes ; Tissue Distribution ; Transduction, Genetic ; Transfection ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><ispartof>Gene therapy, 2004-03, Vol.11 (5), p.457-464</ispartof><rights>2004 INIST-CNRS</rights><rights>COPYRIGHT 2004 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2004</rights><rights>Nature Publishing Group 2004.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c576t-ff68366cb2f70986b2eeac64b44a09f4ef7664c322d5881cec76c5f98ca9c2943</citedby><cites>FETCH-LOGICAL-c576t-ff68366cb2f70986b2eeac64b44a09f4ef7664c322d5881cec76c5f98ca9c2943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15767081$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14973539$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>VAN ROSSENBERG, S. M. W</creatorcontrib><creatorcontrib>VAN KEULEN, A. C. I</creatorcontrib><creatorcontrib>DRIJFHOUT, J.-W</creatorcontrib><creatorcontrib>VASTO, S</creatorcontrib><creatorcontrib>KOERTEN, H. K</creatorcontrib><creatorcontrib>SPIES, F</creatorcontrib><creatorcontrib>VAN'T NOORDENDE, J. M</creatorcontrib><creatorcontrib>VAN BERKEL, T. H. J. C</creatorcontrib><creatorcontrib>BIESSEN, E. A. L</creatorcontrib><title>Stable polyplexes based on arginine-containing oligopeptides for in vivo gene delivery</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><description>In this study, we investigated to what extent the stability and transduction capacity of polyplexed DNA can be improved by optimizing the condensing peptide sequence. We have synthesized a small library of cationic peptides, at which the lysine/arginine ratio and the cation charge were varied. All peptides were able to compact DNA, at which polyplexes of short lysine-rich sequences were considerably larger than those of elongated or arginine-rich peptides (GM102 and GM202). In addition, the arginine-rich peptides GM102 and GM202 rendered the polyplexes resistant to plasma incubation or DNase I-mediated digestion. While all peptides were found to improve the transfection efficiency in HepG2 cells, only the GM102- and GM202-derived polyplexes could be specifically targeted to HepG2 cells by incorporation of a ligand-derivatized YKAK(8)WK peptide. We propose that GM102 and GM202 combine the advantage of small condensing peptides to give small-sized polyplexes with the superior stability of condensing polymers, which makes GM102 and GM202 excellent candidates for future in vivo gene therapy studies.</description><subject>Amino Acid Sequence</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>Arginine</subject><subject>Arginine - chemistry</subject><subject>arginine-rich peptides</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Cationic peptides</subject><subject>Chemical Phenomena</subject><subject>Chemistry, Physical</subject><subject>Deoxyribonuclease</subject><subject>Deoxyribonuclease I - chemistry</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Drug Stability</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Targeting - methods</subject><subject>Gene therapy</subject><subject>Gene transfer</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Vectors - chemistry</subject><subject>Genetic Vectors - pharmacokinetics</subject><subject>Health. Pharmaceutical industry</subject><subject>Humans</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Lysine</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Sequence Data</subject><subject>Nucleotide sequence</subject><subject>Oligopeptides</subject><subject>Oligopeptides - chemistry</subject><subject>Oligopeptides - genetics</subject><subject>Oligopeptides - pharmacokinetics</subject><subject>Peptide Fragments - chemistry</subject><subject>Peptides</subject><subject>polyplexes</subject><subject>Tissue Distribution</subject><subject>Transduction, Genetic</subject><subject>Transfection</subject><subject>Transfusions. Complications. Transfusion reactions. 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M. W ; VAN KEULEN, A. C. I ; DRIJFHOUT, J.-W ; VASTO, S ; KOERTEN, H. K ; SPIES, F ; VAN'T NOORDENDE, J. M ; VAN BERKEL, T. H. J. C ; BIESSEN, E. A. L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c576t-ff68366cb2f70986b2eeac64b44a09f4ef7664c322d5881cec76c5f98ca9c2943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Amino Acid Sequence</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Applied cell therapy and gene therapy</topic><topic>Arginine</topic><topic>Arginine - chemistry</topic><topic>arginine-rich peptides</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Cationic peptides</topic><topic>Chemical Phenomena</topic><topic>Chemistry, Physical</topic><topic>Deoxyribonuclease</topic><topic>Deoxyribonuclease I - chemistry</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Drug Stability</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Targeting - methods</topic><topic>Gene therapy</topic><topic>Gene transfer</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Vectors - chemistry</topic><topic>Genetic Vectors - pharmacokinetics</topic><topic>Health. Pharmaceutical industry</topic><topic>Humans</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Lysine</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular Sequence Data</topic><topic>Nucleotide sequence</topic><topic>Oligopeptides</topic><topic>Oligopeptides - chemistry</topic><topic>Oligopeptides - genetics</topic><topic>Oligopeptides - pharmacokinetics</topic><topic>Peptide Fragments - chemistry</topic><topic>Peptides</topic><topic>polyplexes</topic><topic>Tissue Distribution</topic><topic>Transduction, Genetic</topic><topic>Transfection</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VAN ROSSENBERG, S. M. W</creatorcontrib><creatorcontrib>VAN KEULEN, A. C. I</creatorcontrib><creatorcontrib>DRIJFHOUT, J.-W</creatorcontrib><creatorcontrib>VASTO, S</creatorcontrib><creatorcontrib>KOERTEN, H. 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M. W</au><au>VAN KEULEN, A. C. I</au><au>DRIJFHOUT, J.-W</au><au>VASTO, S</au><au>KOERTEN, H. K</au><au>SPIES, F</au><au>VAN'T NOORDENDE, J. M</au><au>VAN BERKEL, T. H. J. C</au><au>BIESSEN, E. A. L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stable polyplexes based on arginine-containing oligopeptides for in vivo gene delivery</atitle><jtitle>Gene therapy</jtitle><addtitle>Gene Ther</addtitle><date>2004-03-01</date><risdate>2004</risdate><volume>11</volume><issue>5</issue><spage>457</spage><epage>464</epage><pages>457-464</pages><issn>0969-7128</issn><eissn>1476-5462</eissn><abstract>In this study, we investigated to what extent the stability and transduction capacity of polyplexed DNA can be improved by optimizing the condensing peptide sequence. We have synthesized a small library of cationic peptides, at which the lysine/arginine ratio and the cation charge were varied. 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| identifier | ISSN: 0969-7128 |
| ispartof | Gene therapy, 2004-03, Vol.11 (5), p.457-464 |
| issn | 0969-7128 1476-5462 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Applied cell therapy and gene therapy Arginine Arginine - chemistry arginine-rich peptides Biological and medical sciences Biotechnology Cationic peptides Chemical Phenomena Chemistry, Physical Deoxyribonuclease Deoxyribonuclease I - chemistry Deoxyribonucleic acid DNA Drug Stability Fundamental and applied biological sciences. Psychology Gene Targeting - methods Gene therapy Gene transfer Gene Transfer Techniques Genetic Vectors - chemistry Genetic Vectors - pharmacokinetics Health. Pharmaceutical industry Humans Industrial applications and implications. Economical aspects Lysine Male Medical sciences Mice Mice, Inbred C57BL Molecular Sequence Data Nucleotide sequence Oligopeptides Oligopeptides - chemistry Oligopeptides - genetics Oligopeptides - pharmacokinetics Peptide Fragments - chemistry Peptides polyplexes Tissue Distribution Transduction, Genetic Transfection Transfusions. Complications. Transfusion reactions. Cell and gene therapy |
| title | Stable polyplexes based on arginine-containing oligopeptides for in vivo gene delivery |
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