Revisit complexation between DNA and polyethylenimine — Effect of length of free polycationic chains on gene transfection

Yanan Yue, Fan Jin, Rui Deng, Jinge Cai, Zhuojun Dai, Marie C.M. Lin, Hsiang-Fu Kung, Maria Ahlm Mattebjerg, Thomas Lars Andresen, Chi Wu

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Our revisit of the complexation between DNA and polyethylenimine (PEI) by using a combination of laser light scattering and gel electrophoresis confirms that nearly all the DNA chains are complexed with PEI to form polyplexes when the molar ratio of nitrogen from PEI to phosphate from DNA (N:P) reaches ~3, irrespective of the PEI chain length and solvent. Each solution mixture with N:P>3 contains two kinds of PEI chains: bound to DNA and free in the solution. It has been shown that it is those free PEI chains that play a vital role in promoting the gene transfection. The effects of the length of the bound and free chains on the gene transfection were respectively studied. Both short and long PEI chains are capable of condensing DNA completely at N:P~3 but long ones are ~102-fold more effective in the gene transfection, apparently due to their fast endocytosis and intracellular trafficking. The cellular uptake kinetics studied by flow cytometry reveals that long free chains increase the uptake rate constant of the DNA/PEI complexes. In the intracellular pathway, they are able to prevent the development of the later endolysosomes, and facilitate the subsequent release of the polyplexes from the endosomes. Our result shows that the “proton sponge” effect is not dominant because the shut-down of the proton pump only partially attenuates the transfection efficiency. A possible mechanism is speculated and presented.
    Original languageEnglish
    JournalJournal of Controlled Release
    Volume152
    Issue number1
    Pages (from-to)143-151
    ISSN0168-3659
    DOIs
    Publication statusPublished - 2011
    EventSymposium on Innovative Polymers for Controlled Delivery -
    Duration: 1 Jan 2011 → …

    Conference

    ConferenceSymposium on Innovative Polymers for Controlled Delivery
    Period01/01/2011 → …

    Fingerprint Dive into the research topics of 'Revisit complexation between DNA and polyethylenimine — Effect of length of free polycationic chains on gene transfection'. Together they form a unique fingerprint.

    Cite this