Efficient gene delivery using reconstituted chromatin enhanced for nuclear targeting

Kylie M. Wagstaff, Jun Y. Fan, Michelle A. De Jesus, David J. Tremethick, David A. Jans

    Research output: Contribution to journalArticlepeer-review

    33 Citations (Scopus)

    Abstract

    Nonviral gene delivery is hampered by difficulties associated with transporting negatively charged DNA through the cell membrane and, more importantly, the nuclear envelope of target cells. Here we show for the first time that chromatin reconstituted with histone H2B proteins optimized for nuclear targeting can be used as an efficient means to deliver DNA to the nucleus of intact living mammalian cells, resulting in high levels of transgene expression that were ∼6-fold more than those achieved by commercial liposomal preparations. The high efficiency is due in part to DNA condensation and protection against degradation in the reconstituted chromatin, as well as its ability to interact with high affinity with the importin proteins of the cellular nuclear import machinery. "Chromofection," gene delivery by protein transduction using chromatin enhanced for nuclear targeting represents an efficient means to deliver DNA to a wide variety of cell types, with the potential to treat complex genetic disorders.

    Original languageEnglish
    Pages (from-to)2232-2242
    Number of pages11
    JournalFASEB Journal
    Volume22
    Issue number7
    DOIs
    Publication statusPublished - Jul 2008

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