Role of liposome and peptide in the synergistic enhancement of transfection with a lipopolyplex vector

M.M. Munye, J Ravi, Aristides Tagalakis, D McCarthy, M.G. Ryadnov, S.L. Hart

Research output: Contribution to journalArticle

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Abstract

Lipopolyplexes are of widespread interest for gene therapy due to their multifunctionality and high transfection efficiencies. Here we compared the biological and biophysical properties of a lipopolyplex formulation with its lipoplex and polyplex equivalents to assess the role of the lipid and peptide components in the formation and function of the lipopolyplex formulation. We show that peptide efficiently packaged plasmid DNA forming spherical, highly cationic nanocomplexes that are taken up efficiently by cells. However, transgene expression was poor, most likely due to endosomal degradation since the polyplex lacks membrane trafficking properties. In addition the strong peptide-DNA interaction may prevent plasmid release from the complex and so limit plasmid DNA availability. Lipid/DNA lipoplexes, on the other hand, produced aggregated masses that showed poorer cellular uptake than the polyplex but contrastingly greater levels of transgene expression. This may be due to the greater ability of lipoplexes relative to polyplexes to promote endosomal escape. Lipopolyplex formulations formed spherical, cationic nanocomplexes with efficient cellular uptake and significantly enhanced transfection efficiency. The lipopolyplexes combined the optimal features of lipoplexes and polyplexes showing optimal cell uptake, endosomal escape and availability of plasmid for transcription, thus explaining the synergistic increase in transfection efficiency.
Original languageEnglish
JournalScientific Reports
Volume5
Issue number9292
Early online date19 Mar 2015
DOIs
Publication statusE-pub ahead of print - 19 Mar 2015

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Liposomes
Transfection
Plasmids
Peptides
DNA
Transgenes
Lipids
Genetic Therapy
Membranes

Cite this

Munye, M.M. ; Ravi, J ; Tagalakis, Aristides ; McCarthy, D ; Ryadnov, M.G. ; Hart, S.L. / Role of liposome and peptide in the synergistic enhancement of transfection with a lipopolyplex vector. In: Scientific Reports. 2015 ; Vol. 5, No. 9292.
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Role of liposome and peptide in the synergistic enhancement of transfection with a lipopolyplex vector. / Munye, M.M.; Ravi, J; Tagalakis, Aristides; McCarthy, D; Ryadnov, M.G.; Hart, S.L.

In: Scientific Reports, Vol. 5, No. 9292, 19.03.2015.

Research output: Contribution to journalArticle

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AU - Ravi, J

AU - Tagalakis, Aristides

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