Enhanced transfection efficacy of polyethylenimine by surface modification with arginine, lysine, and leucine

Hibah Mobarak Aldawsari, Behin Sundara Raj, Ruangelie Edrada-Ebel, David Blatchford, Rothwelle Tate, Christine Dufès

Research output: Contribution to journalArticle

Abstract

The potential of gene therapy is currently limited by the lack of delivery systems able to efficiently carry therapeutic DNA to their site of action. Non-viral vectors are receiving increasing attention as gene delivery vehicles due to the limitations associated with viral vectors in terms of safety and immunogenicity. Unfortunately, their use is hampered by their lower transfection efficacy compared with viral systems. The present study investigates the possibility of improving transfection by grafting amino acids onto the surface of a non-viral gene delivery system. We chose to use the amino acids arginine, lysine, and leucine because they have been reported to enhance transportation into
cells (1–3). As a model delivery system, we chose to use the polymer polyethylenimine (PEI), because it has been widely used for non-viral transfection in vitro and in vivo and combines strong DNA compaction capacity with an intrinsic endosomolytic activity known as the proton sponge effect (4–5). It is
hypothesized that arginine-, lysine-, and leucine-bearing polyethylenimine would lead to improved transfection efficacy through the synergistic action of the proton sponge effect and hydrophobic interactions with the cellular membranes. The objectives of this study, therefore, are 1) to prepare and
characterize arginine-, lysine-, and leucine-bearing polyethylenimine; 2) to evaluate their transfection and therapeutic efficacies in vitro on the A431 human epidermoid carcinoma cell line; and 3) to evaluate their transfection efficacy in vivo after intravenous administration in mice bearing A431 tumours.
LanguageEnglish
Pages12-14
Number of pages3
JournalControlled Release Society Newsletter
Volume27
Issue number6
StatePublished - 2010

Fingerprint

Polyethyleneimine
Leucine
Lysine
Transfection
Arginine
Porifera
Protons
Amino Acids
Gene Transfer Techniques
DNA
Hydrophobic and Hydrophilic Interactions
Intravenous Administration
Genetic Therapy
Squamous Cell Carcinoma
Polymers
Safety
Cell Line
Membranes
Therapeutics
Genes

Keywords

  • polyethylenimine
  • transfection efficacy
  • gene therapy
  • carcinoma cell

Cite this

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abstract = "The potential of gene therapy is currently limited by the lack of delivery systems able to efficiently carry therapeutic DNA to their site of action. Non-viral vectors are receiving increasing attention as gene delivery vehicles due to the limitations associated with viral vectors in terms of safety and immunogenicity. Unfortunately, their use is hampered by their lower transfection efficacy compared with viral systems. The present study investigates the possibility of improving transfection by grafting amino acids onto the surface of a non-viral gene delivery system. We chose to use the amino acids arginine, lysine, and leucine because they have been reported to enhance transportation intocells (1–3). As a model delivery system, we chose to use the polymer polyethylenimine (PEI), because it has been widely used for non-viral transfection in vitro and in vivo and combines strong DNA compaction capacity with an intrinsic endosomolytic activity known as the proton sponge effect (4–5). It ishypothesized that arginine-, lysine-, and leucine-bearing polyethylenimine would lead to improved transfection efficacy through the synergistic action of the proton sponge effect and hydrophobic interactions with the cellular membranes. The objectives of this study, therefore, are 1) to prepare andcharacterize arginine-, lysine-, and leucine-bearing polyethylenimine; 2) to evaluate their transfection and therapeutic efficacies in vitro on the A431 human epidermoid carcinoma cell line; and 3) to evaluate their transfection efficacy in vivo after intravenous administration in mice bearing A431 tumours.",
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Enhanced transfection efficacy of polyethylenimine by surface modification with arginine, lysine, and leucine. / Aldawsari, Hibah Mobarak; Sundara Raj, Behin; Edrada-Ebel, Ruangelie; Blatchford, David; Tate, Rothwelle; Dufès, Christine.

In: Controlled Release Society Newsletter, Vol. 27, No. 6, 2010, p. 12-14.

Research output: Contribution to journalArticle

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AU - Aldawsari,Hibah Mobarak

AU - Sundara Raj,Behin

AU - Edrada-Ebel,Ruangelie

AU - Blatchford,David

AU - Tate,Rothwelle

AU - Dufès,Christine

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