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Polyarginine Molecular Weight Determines Transfecion Efficiency of Calcium Condensed Complexes
Alhakamy, Nabil A. Berkland, Cory J.
Alhakamy, Nabil A.
Berkland, Cory J.
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Abstract
Cell penetrating peptides (CPPs) have been extensively studied in polyelectrolyte complexes as a means to enhance the transfection efficiency of plasmid DNA (pDNA). Increasing the molecular weight of CPPs often enhances gene expression, but poses a risk of increased cytotoxicity and immunogenicity compared to low molecular weight CCPs. Conversely, low molecular weight CPPs typically have low transfection efficiency due to large complex size. Complexes made using low molecular weight CPPs were found to be condensed to a small size by adding calcium. In this study, complexes of low molecular weight polyarginine and pDNA were condensed with calcium. These complexes showed high transfection efficiency and low cytotoxicity in A549 carcinomic human alveolar basal epithelial cells. The relationship between transfection efficiency and polyarginine size (5, 7, 9 or 11 amino acids), polyarginine/pDNA charge ratios, and calcium concentrations were studied. Polyarginine 7 was significantly more effective than other polyarginines under most formulation conditions suggesting a link between cell penetration ability and transfection efficiency.
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2013-05-06
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American Chemical Society
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Alhakamy_2013.pdf
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Keywords
Plasmid DNA, Polyarginine, Cell-penetrating peptides, A549 cells, Non-viral gene delivery, Calcium chloride, Transfection
Citation
Alhakamy, N. A., & Berkland, C. J. (2013). Polyarginine Molecular Weight Determines Transfection Efficiency of Calcium Condensed Complexes. Molecular Pharmaceutics, 10(5), 1940–1948. http://doi.org/10.1021/mp3007117