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The role of the helper lipid on the DNA transfection efficiency of lipopolyplex formulations.

Multifunctional, lipopolyplex formulations comprising a mixture of cationic liposomes and cationic, receptor-targeting peptides have potential use in gene therapy applications. Lipopolyplex formulations described here are typically far more efficient transfection agents than binary lipoplex or polyp... Full description

Journal Title: Scientific reports November 19, 2014, Vol.4, p.7107
Main Author: Du, Zixiu
Other Authors: Munye, Mustafa M , Tagalakis, Aristides D , Manunta, Maria D I , Hart, Stephen L
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 2045-2322 ; DOI: 10.1038/srep07107
Link: http://search.proquest.com/docview/1627075232/?pq-origsite=primo
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title: The role of the helper lipid on the DNA transfection efficiency of lipopolyplex formulations.
format: Article
creator:
  • Du, Zixiu
  • Munye, Mustafa M
  • Tagalakis, Aristides D
  • Manunta, Maria D I
  • Hart, Stephen L
subjects:
  • Animals–Metabolism
  • Cell Line–Chemistry
  • Cell Nucleus–Metabolism
  • DNA–Chemistry
  • Endosomes–Administration & Dosage
  • Fatty Acids, Monounsaturated–Chemistry
  • Female–Administration & Dosage
  • Humans–Chemistry
  • Lipid Bilayers–Metabolism
  • Liposomes–Chemistry
  • Lung–Chemistry
  • Membrane Fusion–Chemistry
  • Mice–Chemistry
  • Peptides–Cytology
  • Phosphatidylcholines–Metabolism
  • Phosphatidylethanolamines–Methods
  • Quaternary Ammonium Compounds–Methods
  • Respiratory Mucosa
ispartof: Scientific reports, November 19, 2014, Vol.4, p.7107
description: Multifunctional, lipopolyplex formulations comprising a mixture of cationic liposomes and cationic, receptor-targeting peptides have potential use in gene therapy applications. Lipopolyplex formulations described here are typically far more efficient transfection agents than binary lipoplex or polyplex formulations. It has been shown previously that the peptide component mediates both DNA packaging and targeting of the nanoparticle while in this report we investigate the contribution of the lipid component. We hypothesised that the lipid components synergise with the peptides in the transfection process by promoting endosomal escape after lipid bilayer fusion. Lipopolyplexes were prepared with cationic liposomes comprising DOTAP with either neutral lipid DOPE or DOPC. DOPE promotes fusogenic, inverted hexagonal lipid structures while DOPC promotes more stable laminar structures. Lipopolyplexes containing DOPE showed substantially higher transfection efficiency than those formulated with DOPC, both in vitro and in vivo. DOPE-containing lipopolyplexes showed rapid endosomal trafficking and nuclear accumulation of DNA while DOPC-containing formulations remained within the late endo-lysosomal compartments. These findings are consistent with previous finding for the role of DOPE in lipoplexes and support the hypothesis regarding the function of the lipid components in lipopolyplexes. These findings will help to inform future lipopolyplex design, strategies and clinical development processes.
language: eng
source:
identifier: E-ISSN: 2045-2322 ; DOI: 10.1038/srep07107
fulltext: fulltext
issn:
  • 20452322
  • 2045-2322
url: Link


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titleThe role of the helper lipid on the DNA transfection efficiency of lipopolyplex formulations.
creatorDu, Zixiu ; Munye, Mustafa M ; Tagalakis, Aristides D ; Manunta, Maria D I ; Hart, Stephen L
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identifierE-ISSN: 2045-2322 ; DOI: 10.1038/srep07107
subjectAnimals–Metabolism ; Cell Line–Chemistry ; Cell Nucleus–Metabolism ; DNA–Chemistry ; Endosomes–Administration & Dosage ; Fatty Acids, Monounsaturated–Chemistry ; Female–Administration & Dosage ; Humans–Chemistry ; Lipid Bilayers–Metabolism ; Liposomes–Chemistry ; Lung–Chemistry ; Membrane Fusion–Chemistry ; Mice–Chemistry ; Peptides–Cytology ; Phosphatidylcholines–Metabolism ; Phosphatidylethanolamines–Methods ; Quaternary Ammonium Compounds–Methods ; Respiratory Mucosa
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descriptionMultifunctional, lipopolyplex formulations comprising a mixture of cationic liposomes and cationic, receptor-targeting peptides have potential use in gene therapy applications. Lipopolyplex formulations described here are typically far more efficient transfection agents than binary lipoplex or polyplex formulations. It has been shown previously that the peptide component mediates both DNA packaging and targeting of the nanoparticle while in this report we investigate the contribution of the lipid component. We hypothesised that the lipid components synergise with the peptides in the transfection process by promoting endosomal escape after lipid bilayer fusion. Lipopolyplexes were prepared with cationic liposomes comprising DOTAP with either neutral lipid DOPE or DOPC. DOPE promotes fusogenic, inverted hexagonal lipid structures while DOPC promotes more stable laminar structures. Lipopolyplexes containing DOPE showed substantially higher transfection efficiency than those formulated with DOPC, both in vitro and in vivo. DOPE-containing lipopolyplexes showed rapid endosomal trafficking and nuclear accumulation of DNA while DOPC-containing formulations remained within the late endo-lysosomal compartments. These findings are consistent with previous finding for the role of DOPE in lipoplexes and support the hypothesis regarding the function of the lipid components in lipopolyplexes. These findings will help to inform future lipopolyplex design, strategies and clinical development processes.
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