A composite gene delivery system consisting of polyethylenimine and an amphipathic peptide KALA

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Title
A composite gene delivery system consisting of polyethylenimine and an amphipathic peptide KALA
Author(s)
S H Min; Dong Chul Lee; M J Lim; H S Park; D M Kim; C W Cho; D Y Yoon; Young Il Yeom
Bibliographic Citation
Journal of Gene Medicine, vol. 8, no. 12, pp. 1425-1434
Publication Year
2006
Abstract
Background: Animal viruses such as enveloped virus carry multi-functional proteins in the virion that can mediate more than two distinct steps of a gene delivery process during the transfer of viral genome into host cells. We tested if the aspects of the viral gene delivery mechanism could be mimicked by forming composite formulae from multi-functional synthetic gene carriers having complementary action modes. Methods: Polyethylenimine (PEI) was chosen as the component responsible for endosome escape and DNA condensation and KAIA for cellular entry and DNA condensation. Compact DNA-carrier particles consisting of the core part where DNA chains were tightly condensed by PEI and the outer layer lined with KALA were formulated, characterized and compared with monolithic cationic formulae in terms of gene delivery efficiency and mechanism. Results: High-level gene expression was observed when C2C12 cells were transfected with DNA that was first partially condensed with PEI and, then, fully with KALA. In these formulae KALA mediated enhanced cellular entry of DNA by facilitating endocytic vesicle formation, while PEI provided an effective endosomolytic capacity. An optimal PEI/KALA formula showed transfection efficiencies better than or comparable to the commercial cationic liposome in various cell types in culture and in vivo. Conclusions: Gene delivery by combining the membrane-active property of KALA with the endosomolytic activity of PEI can be more efficient than that by either of the properties alone. It appears that, in these formulae, the predominant role of KALA is to facilitate cellular entry of DNA by providing a fusogenic capability, rather than an endosomolytic activity.
Keyword
Fusogenic peptideGene deliveryKALANonviral vectorPEIPolyethylenimine
ISSN
1099-498X
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/jgm.973
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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