A simple protocol for preparation of a liposomal vesicle with encapsulated plasmid DNA that mediate high accumulation and reporter gene activity in tumor tissue

Torben Gjetting, Thomas Lars Andresen, Camilla Laulund Christensen, Frederik Cramer, Thomas Tuxen Poulsen, Hans Skovgaard Poulsen

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    The systemic delivery of gene therapeutics by non-viral methods has proven difficult. Transfection systems that are performing well in vitro have been reported to have disadvantageous properties such as rapid clearance and short circulation time often resulting in poor transfection efficiency when applied in vivo. Large unilaminary vesicles (LUV) with encapsulated nucleic acids designated stabilizedplasmid- lipo-particle (SPLP) have showed promising results in terms of systemic stability and accumulation in tumor tissue due to the enhanced permeability and retention effect (EPR). We have developed a simple protocol for the research-scale preparation of SPLPs from commercially available reagents with high amounts of encapsulated plasmid DNA. The SPLPs show properties of promising accumulation in tumor tissue in comparison to other organs when intravenously injected into xenograft tumor-bearing nude mice. Although transcriptionally targeted suicide gene therapy was not achieved, the SPLPs were capable of mediating reporter gene transfection in subcutaneous flank tumors originating from human small cell lung cancer.
    Original languageEnglish
    JournalResults in Pharma Sciences
    Volume1
    Pages (from-to)49-56
    ISSN2211-2863
    DOIs
    Publication statusPublished - 2011

    Keywords

    • Biodistribution
    • Gene delivery
    • Stabilized plasmid–lipid particle (SPLP)
    • Suicide gene therapy
    • Liposome
    • Xenograft tumor model

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