Stable Binding of DNA to Zwitterionic Lipid Bilayers in Aqueous Solutions

Malghani, M. S.; Yang, Jie

doi:10.1021/jp982413g

Cited by 32 publications

(36 citation statements)

References 24 publications

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“…This study also predicted equal probabilities for the existence of TAP or PC groups around DNA phosphates. Stable binding of DNA to PC bilayers due to the tethering of DNA by the PC headgroup has also been reported (37). Interestingly, this binding was drastically reduced by a brief exposure to 1 M NaCl because of the screening of the attractive forces between DNA phosphates and PC nitrogens by high concentrations of monovalent ions.…”

Section: Discussionmentioning

confidence: 75%

Neurons Are Protected from Excitotoxic Death by p53 Antisense Oligonucleotides Delivered in Anionic Liposomes

Lakkaraju¹,

Dubinsky²,

Low³

et al. 2001

Journal of Biological Chemistry

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The potential of anionic liposomes for oligonucleotide delivery was explored because the requirement for a net-positive charge on transfection-competent cationic liposome-DNA complexes is ambiguous. Liposomes composed of phosphatidylglycerol and phosphatidylcholine were monodisperse and encapsulated oligonucleotides with 40 -60% efficiency. Ionic strength, bilayer charge density, and oligonucleotide chemistry influenced encapsulation. To demonstrate the biological efficacy of this vector, antisense oligonucleotides to p53 delivered in anionic liposomes were tested in an in vitro model of excitotoxicity. Exposure of hippocampal neurons to glutamate increased p53 protein expression 4-fold and decreased neuronal survival to ϳ35%. Treatment with 1 M p53 antisense oligonucleotides in anionic liposomes prevented glutamate-induced up-regulation of p53 and increased neuronal survival to ϳ75%. Selective inhibition of gene expression with antisense oligonucleotides (AsONs) 1 is both a popular technique for probing fundamental questions of neuroscience (1) and a potential therapeutic strategy for the treatment of neurodegenerative diseases (2). However, the elegance of the antisense concept belies the considerable challenge of their intracellular delivery (3). Chemical modifications of ONs that enhance nuclease-resistance (e.g. phosphorothioates) have poor cellular uptake (ϳ5-10%) and cause non-sequence-specific effects, raising questions about the efficacy and selectivity of antisense drugs (4). Cationic lipids and polycationic polymers used as ON delivery vectors have met with limited success due to a number of variables that seem to affect vector performance (3, 5). Mechanistic aspects of cationic lipid-mediated delivery are poorly understood because of the physical heterogeneity of cationic lipid-ON complexes (6) that may contribute to their toxicity toward several cell types (7). Application of antisense technology to the nervous system presents an even greater challenge because of the post-mitotic nature of neurons and their exquisite sensitivity to their microenvironment. Cationic lipids and polymers have been used to deliver nucleic acids to neurons, generally at efficiencies of 0.5-5% (8). Factors that influence transgene expression or target protein inhibition include neuronal maturity at the time of transfection, the type of cationic lipid used (8), and the net charge of the lipid-DNA complex (9). Cationic lipids per se have also been reported to be toxic to neurons (8, 10).Glutamate, the main excitatory neurotransmitter in the brain, plays a central role in the pathogenesis of stroke, epilepsy, and neurodegenerative diseases such as Alzheimer's disease. Excitotoxicity results in increased translation (11) and stabilization (12) of the p53 protein, which in turn alters the levels of redox proteins (13), resulting in neuronal loss. p53 has also been shown to accumulate in mitochondria, leading to mitochondrial dysfunction and activation of the caspase cascade (14). As further proof of the involvement of p53 in ne...

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Section: Discussionmentioning

confidence: 75%

Neurons Are Protected from Excitotoxic Death by p53 Antisense Oligonucleotides Delivered in Anionic Liposomes

Lakkaraju¹,

Dubinsky²,

Low³

et al. 2001

Journal of Biological Chemistry

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“…Although double-stranded DNA (dsDNA) has been shown to bind to zwitterionic lipids (Malghani and Yang, 1998), its thermodynamic stability features remain to be elucidated. Only results obtained with unilamellar DPPC vesicles have been presented, in the light of recent evidence for their better performance in gene delivery studies with respect to internalization mechanisms (Templeton, 2001).…”

Section: Resultsmentioning

confidence: 99%

Adiabatic differential scanning calorimetric study of divalent cation induced DNA - DPPC liposome formulation compacted for gene delivery

Süleymanoglu

2004

Braz. arch. biol. technol.

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“…Safinya's investigations also revealed that the L C -H II C phase transition could be mediated by changing the spontaneous curvatures of lipids and membrane rigidity [5]. Since the synthetic cationic lipids are toxic to cell, using liposomes completely composed of zwitterionic lipids (ZL) has been progressively examined as a promising alternative to cationic lipids [14][15][16][17][18][19][20][21][22][23][24][25]. Nevertheless owing to weak interactions, when DNA is added into ZL aqueous solution, only a small amount of DNA is capable of entrapped within the ZL liposomes [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

“…Since the synthetic cationic lipids are toxic to cell, using liposomes completely composed of zwitterionic lipids (ZL) has been progressively examined as a promising alternative to cationic lipids [14][15][16][17][18][19][20][21][22][23][24][25]. Nevertheless owing to weak interactions, when DNA is added into ZL aqueous solution, only a small amount of DNA is capable of entrapped within the ZL liposomes [23][24][25]. Recently, to enhance the DNA-ZL interaction, divalent metal cations (M n 2+ ) have been used to bridge DNA and ZLs [17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

“…Despite its promising application in medicinal field, not many studies have been carried out to explore the morphologies formed by pure binary DNA-ZL systems [15,16,24,25]. Malghani and Yang were the first to show using atomic force microscopy (AFM) that DNA isotropically adsorbs on the surface of the gel-state DPPC supported film in the aqueous NaCl solution through electrostatic attractions [24].…”

Section: Introductionmentioning

confidence: 99%

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Nanostructures and Thermal Properties of the Binary Mixture of DNA and a Zwitterionic Phospholipid in the Bulk

Wu¹

2012

J. Appl. Sol. Chem. Model.

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The mixtures of polyanionic DNA and zwitterionic phospholipids (ZL) have recently received much attention because of their potential for use as vectors in gene therapy or as a template for nanostructure construction. The past few studies on DNA-ZL system were carried out in their aqueous solutions and it was reported that a small fraction of DNA was capable of binding to zwitterionic lipids. However, it is still not known whether, as in the aqueous state, the DNA will be still intercalated between lipid bilayers in the bulk state. In the present study, we examined the DNA-ZL interactions in the bulk state by investigating a binary system composing of DNA and a zwitterionic lipid, 1,2-di(cis-9octadecenoyl)-sn-glycero-3-phosphocholine (DOPC). The nanostructures and thermotropic phase behavior of this system were investigated using small angle X-ray scattering (SAXS) and differential scanning calorimeter (DSC), respectively. Our SAXS with one-dimensional correlation function results revealed that, as in the aqueous state, the DNA/DOPC bulk mixture forms a multilamellar phase, where the DNA was confined between the DOPC lipid bilayers. The thickness of the hydrophobic layers composed of lipids tails was greater in the DNA-DOPC mixture than in the pure DOPC. However, interestingly, the thickness of the hydrophilic layer composed of lipid headgroups in the DNA-DOPC mixture was same as in the pure DOPC even though in the former DNA was intercalated in this layer. Furthermore, according to the DSC endotherms we also observe that DNA induced a significant depression of gel-to-liquid crystalline phase transition temperature of DOPC bilayer. A thermodynamic model was presented that described the experimentally observed morphological and thermotropic phase behavior.

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Stable Binding of DNA to Zwitterionic Lipid Bilayers in Aqueous Solutions

Cited by 32 publications

References 24 publications

Neurons Are Protected from Excitotoxic Death by p53 Antisense Oligonucleotides Delivered in Anionic Liposomes

Neurons Are Protected from Excitotoxic Death by p53 Antisense Oligonucleotides Delivered in Anionic Liposomes

Adiabatic differential scanning calorimetric study of divalent cation induced DNA - DPPC liposome formulation compacted for gene delivery

Nanostructures and Thermal Properties of the Binary Mixture of DNA and a Zwitterionic Phospholipid in the Bulk

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