1. Quantized Folding of Plasmid DNA Condensed with Block Catiomer into Characteristic Rod Structures Promoting Transgene Efficacy
- Author
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Kensuke Osada, Daigo Kobayashi, Motoyoshi Doi, Manabu Enoki, Hiroki Oshima, Kazunori Kataoka, and Yuichi Yamasaki
- Subjects
Molecular Structure ,Lysine ,Transgene ,DNA ,General Chemistry ,Biochemistry ,Molecular biology ,Catalysis ,Polyethylene Glycols ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,chemistry ,Plasmid dna ,Transcription (biology) ,Gene expression ,PEG ratio ,Biophysics ,Nucleic Acid Conformation ,DNA supercoil ,Ethylene glycol ,Plasmids - Abstract
Highly regulated folding of plasmid DNA (pDNA) through polyion complexation with the synthetic block catiomer, poly(ethylene glycol)-block-poly(L-lysine) (PEG-PLys), was found to occur in such a way that rod structures are formed with a quantized length of 1/2(n + 1) of the original pDNA length folding by n times. The folding process of pDNA was elucidated with regard to rigidity of the double-stranded DNA structure and topological restriction of the supercoiled closed-circular form, and a mechanism based on Euler's buckling theory was proposed. Folded pDNA exhibited higher gene expression efficiency compared to naked pDNA in a cell-free transcription/translation assay system, indicating that the packaging of pDNA into a polyion complex core surrounded by a PEG palisade is a promising strategy for constructing nonviral gene carrier systems. Extension of this finding may provide a reasonable model to further understand the packaging mechanism of supercoiled DNA structures in nature.
- Published
- 2010