Cancer Institute A national cancer institute
designated cancer center

Christopher H. Contag

Publication Details

  • Increased interstitial pressure improves nucleic acid delivery to skin enabling a comparative analysis of constitutive promoters GENE THERAPY Gonzalez-Gonzalez, E., Ra, H., Spitler, R., Hickerson, R. P., Contag, C. H., Kaspar, R. L. 2010; 17 (10): 1270-1278

    Abstract:

    Nucleic acid-based therapies hold great promise for treatment of skin disorders if delivery challenges can be overcome. To investigate one mechanism of nucleic acid delivery to keratinocytes, a fixed mass of expression plasmid was intradermally injected into mouse footpads in different volumes, and reporter expression was monitored by intravital imaging or skin sectioning. Reporter gene expression increased with higher delivery volumes, suggesting that pressure drives nucleic acid uptake into cells after intradermal injections similar to previously published studies for muscle and liver. For spatiotemporal analysis of reporter gene expression, a dual-axis confocal (DAC) fluorescence microscope was used for intravital imaging following intradermal injections. Individual keratinocytes expressing hMGFP were readily visualized in vivo and initially appeared to preferentially express in the stratum granulosum and subsequently migrate to the stratum corneum over time. Fluorescence microscopy of frozen skin sections confirmed the patterns observed by intravital imaging. Intravital imaging with the DAC microscope is a noninvasive method for probing spatiotemporal control of gene expression and should facilitate development and testing of new nucleic acid delivery technologies.

    View details for DOI 10.1038/gt.2010.74

    View details for Web of Science ID 000282948600011

    View details for PubMedID 20463756

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