Phase Behavior, DNA Ordering, and Size Instability of Cationic Lipoplexes

Simberg, Dmitri; Danino, Dganit; Talmon, Yeshayahu; Minsky, Abraham; Ferrari, Marilyn E.; Wheeler, Carl J.; Barenholz, Yechezkel

doi:10.1074/jbc.m105588200

Cited by 183 publications

(178 citation statements)

References 34 publications

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“…These are commonly employed as vectors for non-viral gene delivery for therapeutic purposes, as they are effective in the condensation and transfection of genetic material [11]. Among others, cationic bolaamphiphiles are attractive targets for the development of novel agents for nucleic acid delivery.…”

Section: Introductionmentioning

confidence: 99%

Interaction between a cationic bolaamphiphile and DNA: The route towards nanovectors for oligonucleotide antimicrobials

Mamusa

Resta

Barbero³

et al. 2016

Colloids and Surfaces B: Biointerfaces

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Section: Introductionmentioning

confidence: 99%

Interaction between a cationic bolaamphiphile and DNA: The route towards nanovectors for oligonucleotide antimicrobials

Mamusa

Resta

Barbero³

et al. 2016

Colloids and Surfaces B: Biointerfaces

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“…Cationic lipids and cationic polymers have been extensively studied for gene transfer experiments, during the last two decades [4][5][6][7][8][9] . In spite of a few limitations, such as a relatively low transfection rate and some intrinsic cell toxicity, these cationic agents are considered as a valid alternative to viral vectors [10][11][12]. Indeed, cationic polymers and liposomes are generally non-immunogenic, easy to produce, and non-oncogenic.…”

Section: Introductionmentioning

confidence: 99%

DOTAP/DOPE and DC-Chol/DOPE lipoplexes for gene delivery studied by circular dichroism and other biophysical techniques

Ciani

Casini

Gabbiani

et al. 2007

Biophysical Chemistry

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Cationic liposomes give rise to stable complexes with DNA molecules ( lipoplexes) that are of great interest for gene delivery applications. In particular, liposomes made up by a cationic lipid (DOTAP or DC-Chol) and a zwitterionic lipid (DOPE), produce stable adducts with single and double -stranded DNA oligonucleotides. Formation of these lipople xes has been further addressed here by circular dichroism spectroscopy (CD) and by other independent biophysical methods. Titration of DNA oligonucleotides with cationic liposomes resulted into significant modifications of their circular dichroic bands. Such spectral modifications were ascribed to progressive DNA condensation and loss of native conformation, as a consequence of the electrostatic interactions taking place between the phosphate groups of DNA and the positively charged head groups of cationic lipids. In all cases, the loss of the CD features characteristic of the native DNA conformation closely matched the inflection point of zeta potential profiles. The resulting adducts showed peculiar and non-canonical CD spectra, while exhibiting appreciable stability at physiological pH.

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“…A useful starting point is the physics governing the analogous CL-DNA complexes (7,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). DNA and CLs self-assemble into condensed multilamellar complexes, where parallel DNA chains are confined between lipid sheets (14,15).…”

mentioning

confidence: 99%

Polymorphism of DNA–anionic liposome complexes reveals hierarchy of ion-mediated interactions

Liang

Harries

Wong

2005

Proc. Natl. Acad. Sci. U.S.A.

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Self-assembled DNA delivery systems based on anionic lipids (ALs) complexed with DNA mediated by divalent cations have been recently introduced as an alternative to cationic lipid-DNA complexes because of their low cytotoxicity. We investigate AL-DNA complexes induced by different cations by using synchrotron small angle x-ray scattering and confocal microscopy to show how different ion-mediated interactions are expressed in the selfassembled structures and phase behavior of AL-DNA complexes. The governing interactions in AL-DNA systems are complex: divalent ions can mediate strong attractions between different combinations of the components (such as DNA-DNA and membrane-membrane). Moreover, divalent cations can coordinate nonelectrostatically with lipids and modify the resultant membrane structure. We find that at low membrane charge densities AL-DNA complexes organize into a lamellar structure of alternating DNA and membrane layers crosslinked by ions. At high membrane charge densities, a new phase with no analog in cationic lipid-DNA systems is observed: DNA is expelled from the complex, and a lamellar stack of membranes and intercalated ions is formed. For a subset of the ionic species, high ion concentrations generate an inverted hexagonal phase comprised of DNA strands wrapped by ion-coated lipid tubes. A simple theoretical model that takes into account the electrostatic and membrane elastic contributions to the free energy shows that this transition is consistent with an ion-induced change in the membrane spontaneous curvature, c 0. Moreover, the crossover between the lamellar and inverted hexagonal phases occurs at a critical c0 that agrees well with experimental values.colloids ͉ like-charge attraction ͉ membrane ͉ self-assembly ͉ x-ray G ene therapy using either viral or synthetic vectors is currently one of the most promising strategies for developing cures for many hereditary and acquired diseases. Protocols have been approved for cancer, hemophilia, cystic fibrosis, neuromuscular disorders, and others (1). Although synthetic nonviral systems such as cationic liposomes generally transfect less efficiently than viruses, they have a number of advantages, such as high DNA packaging capacity and low immunogenicity. Cationic lipid (CL)-DNA complexes have emerged as one of the major nonviral DNA delivery platforms (1-7) and have been used to transfect a broad range of cell types and to deliver to cancer vaccines (8-10).Anionic lipids (ALs) occur naturally in eukaryotic cell membranes, and DNA delivery systems based on ALs have recently been examined as an alternative to CLs because of their low cytotoxicity (11-13). ALs can be complexed with anionic DNA via interaction with multivalent cations such as Ca 2ϩ and have been shown to successfully transfer oligonucleotides. An outstanding problem of this approach is the inefficient association between the ALs and DNA molecules, which is attributed to their like-charge electrostatic repulsion.Rational design of AL-DNA vectors requires a coherent understanding of...

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Phase Behavior, DNA Ordering, and Size Instability of Cationic Lipoplexes

Cited by 183 publications

References 34 publications

Interaction between a cationic bolaamphiphile and DNA: The route towards nanovectors for oligonucleotide antimicrobials

Interaction between a cationic bolaamphiphile and DNA: The route towards nanovectors for oligonucleotide antimicrobials

DOTAP/DOPE and DC-Chol/DOPE lipoplexes for gene delivery studied by circular dichroism and other biophysical techniques

Polymorphism of DNA–anionic liposome complexes reveals hierarchy of ion-mediated interactions

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