Phospholipid-Based Artificial Viruses Assembled by Multivalent Cations
Self-assembled DNA delivery systems based on cationic lipids are simple to produce and weakly hazardous in comparison with viral vectors, but possess a significant toxicity at high doses. Phospholipids are in contrast intrinsically safe; yet their association with DNA is problematic because of unfav...
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| Published in | Biophysical journal Vol. 93; no. 2; pp. 637 - 644 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
15.07.2007
Biophysical Society The Biophysical Society |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Self-assembled DNA delivery systems based on cationic lipids are simple to produce and weakly hazardous in comparison with viral vectors, but possess a significant toxicity at high doses. Phospholipids are in contrast intrinsically safe; yet their association with DNA is problematic because of unfavorable electrostatic interactions. We achieve the phospholipid-DNA complexation through the like-charge attraction induced by cations. Monovalent cations are inappropriate due to their poor binding affinity with lipids as inferred from electrophoretic mobility, whereas x-ray diffractions reveal that with multivalent cations, DNA is complexed within an inverted hexagonal liquid-crystalline phase. Coarse-grained Monte Carlo simulations confirm the self-assembly of a DNA rod wrapped into a lipid layer with cations in between acting as molecular glue. Transfection experiments performed with Ca2+ and La3+ demonstrate efficiencies surpassing those obtained with optimized cationic DOTAP-based systems, while preserving the viability of cells. Inspired by bacteriophages that resort to polycations to compact their genetic materials, complexes assembled with tetravalent spermine achieve unprecedented transfection efficiencies for phospholipids. Influence of complex growth time, lipid/DNA mass ratio, and ion concentration are examined. These complexes may initiate new developments for nontoxic gene delivery and fundamental studies of biological self-assembly. |
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| AbstractList | Self-assembled DNA delivery systems based on cationic lipids are simple to produce and weakly hazardous in comparison with viral vectors, but possess a significant toxicity at high doses. Phospholipids are in contrast intrinsically safe; yet their association with DNA is problematic because of unfavorable electrostatic interactions. We achieve the phospholipid-DNA complexation through the like-charge attraction induced by cations. Monovalent cations are inappropriate due to their poor binding affinity with lipids as inferred from electrophoretic mobility, whereas x-ray diffractions reveal that with multivalent cations, DNA is complexed within an inverted hexagonal liquid-crystalline phase. Coarse-grained Monte Carlo simulations confirm the self-assembly of a DNA rod wrapped into a lipid layer with cations in between acting as molecular glue. Transfection experiments performed with Ca^sup 2+^ and La^sup 3+^ demonstrate efficiencies surpassing those obtained with optimized cationic DOTAP-based systems, while preserving the viability of cells. Inspired by bacteriophages that resort to polycations to compact their genetic materials, complexes assembled with tetravalent spermine achieve unprecedented transfection efficiencies for phospholipids. Influence of complex growth time, lipid/DNA mass ratio, and ion concentration are examined. These complexes may initiate new developments for nontoxic gene delivery and fundamental studies of biological self-assembly. [PUBLICATION ABSTRACT] Self-assembled DNA delivery systems based on cationic lipids are simple to produce and weakly hazardous in comparison with viral vectors, but possess a significant toxicity at high doses. Phospholipids are in contrast intrinsically safe; yet their association with DNA is problematic because of unfavorable electrostatic interactions. We achieve the phospholipid-DNA complexation through the like-charge attraction induced by cations. Monovalent cations are inappropriate due to their poor binding affinity with lipids as inferred from electrophoretic mobility, whereas x-ray diffractions reveal that with multivalent cations, DNA is complexed within an inverted hexagonal liquid-crystalline phase. Coarse-grained Monte Carlo simulations confirm the self-assembly of a DNA rod wrapped into a lipid layer with cations in between acting as molecular glue. Transfection experiments performed with Ca super(2+) and La super(3+) demonstrate efficiencies surpassing those obtained with optimized cationic DOTAP-based systems, while preserving the viability of cells. Inspired by bacteriophages that resort to polycations to compact their genetic materials, complexes assembled with tetravalent spermine achieve unprecedented transfection efficiencies for phospholipids. Influence of complex growth time, lipid/DNA mass ratio, and ion concentration are examined. These complexes may initiate new developments for nontoxic gene delivery and fundamental studies of biological self-assembly. Self-assembled DNA delivery systems based on cationic lipids are simple to produce and weakly hazardous in comparison with viral vectors, but possess a significant toxicity at high doses. Phospholipids are in contrast intrinsically safe; yet their association with DNA is problematic because of unfavorable electrostatic interactions. We achieve the phospholipid-DNA complexation through the like-charge attraction induced by cations. Monovalent cations are inappropriate due to their poor binding affinity with lipids as inferred from electrophoretic mobility, whereas x-ray diffractions reveal that with multivalent cations, DNA is complexed within an inverted hexagonal liquid-crystalline phase. Coarse-grained Monte Carlo simulations confirm the self-assembly of a DNA rod wrapped into a lipid layer with cations in between acting as molecular glue. Transfection experiments performed with Ca2+ and La3+ demonstrate efficiencies surpassing those obtained with optimized cationic DOTAP-based systems, while preserving the viability of cells. Inspired by bacteriophages that resort to polycations to compact their genetic materials, complexes assembled with tetravalent spermine achieve unprecedented transfection efficiencies for phospholipids. Influence of complex growth time, lipid/DNA mass ratio, and ion concentration are examined. These complexes may initiate new developments for nontoxic gene delivery and fundamental studies of biological self-assembly. Self-assembled DNA delivery systems based on cationic lipids are simple to produce and weakly hazardous in comparison with viral vectors, but possess a significant toxicity at high doses. Phospholipids are in contrast intrinsically safe; yet their association with DNA is problematic because of unfavorable electrostatic interactions. We achieve the phospholipid-DNA complexation through the like-charge attraction induced by cations. Monovalent cations are inappropriate due to their poor binding affinity with lipids as inferred from electrophoretic mobility, whereas x-ray diffractions reveal that with multivalent cations, DNA is complexed within an inverted hexagonal liquid-crystalline phase. Coarse-grained Monte Carlo simulations confirm the self-assembly of a DNA rod wrapped into a lipid layer with cations in between acting as molecular glue. Transfection experiments performed with Ca 2+ and La 3+ demonstrate efficiencies surpassing those obtained with optimized cationic DOTAP-based systems, while preserving the viability of cells. Inspired by bacteriophages that resort to polycations to compact their genetic materials, complexes assembled with tetravalent spermine achieve unprecedented transfection efficiencies for phospholipids. Influence of complex growth time, lipid/DNA mass ratio, and ion concentration are examined. These complexes may initiate new developments for nontoxic gene delivery and fundamental studies of biological self-assembly. |
| Author | Tresset, Guillaume Ming Lam, Yeng Davy Cheong, Wun Chet Boulaire, Jérôme Shireen Tan, Yan Ling |
| AuthorAffiliation | Institute of Bioengineering and Nanotechnology, Singapore; † Institute of Materials Research and Engineering, Singapore; and ‡ School of Materials Science and Engineering, Nanyang Technological University, Singapore |
| AuthorAffiliation_xml | – name: Institute of Bioengineering and Nanotechnology, Singapore; † Institute of Materials Research and Engineering, Singapore; and ‡ School of Materials Science and Engineering, Nanyang Technological University, Singapore |
| Author_xml | – sequence: 1 givenname: Guillaume surname: Tresset fullname: Tresset, Guillaume email: tguillaume@ibn.a-star.edu.sg organization: Institute of Bioengineering and Nanotechnology, Singapore – sequence: 2 givenname: Wun Chet surname: Davy Cheong fullname: Davy Cheong, Wun Chet organization: Institute of Materials Research and Engineering, Singapore – sequence: 3 givenname: Yan Ling surname: Shireen Tan fullname: Shireen Tan, Yan Ling organization: Institute of Bioengineering and Nanotechnology, Singapore – sequence: 4 givenname: Jérôme surname: Boulaire fullname: Boulaire, Jérôme organization: Institute of Bioengineering and Nanotechnology, Singapore – sequence: 5 givenname: Yeng surname: Ming Lam fullname: Ming Lam, Yeng organization: School of Materials Science and Engineering, Nanyang Technological University, Singapore |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/17483183$$D View this record in MEDLINE/PubMed |
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| Copyright | 2007 The Biophysical Society Copyright Biophysical Society Jul 15, 2007 Copyright © 2007, Biophysical Society |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Editor: Jonathan B. Chaires. Address reprint requests to Guillaume Tresset, 31 Biopolis Way, The Nanos No. 04-01, Singapore 138669. Tel.: 65-6824-7176; Fax: 65-6478-9080; E-mail: tguillaume@ibn.a-star.edu.sg. |
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| SubjectTerms | Biophysical Phenomena Biophysics Cations Cell Line Deoxyribonucleic acid DNA DNA - chemistry DNA - genetics Drug Delivery Systems Electrostatics Genetic Therapy Humans Ions Lipids Macromolecular Substances Membranes, Artificial Models, Molecular Monte Carlo Method Phospholipids - chemistry Supramolecular Assemblies Transfection Viruses - chemistry |
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| Title | Phospholipid-Based Artificial Viruses Assembled by Multivalent Cations |
| URI | https://dx.doi.org/10.1529/biophysj.107.104448 https://www.ncbi.nlm.nih.gov/pubmed/17483183 https://www.proquest.com/docview/215707003 https://search.proquest.com/docview/864396550 https://pubmed.ncbi.nlm.nih.gov/PMC1896246 |
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