Visualization of plasmid delivery to keratinocytes in mouse and human epidermis.

Scientific Reports
E Gonzalez-GonzalezR L Kaspar

Abstract

The accessibility of skin makes it an ideal target organ for nucleic acid-based therapeutics; however, effective patient-friendly delivery remains a major obstacle to clinical utility. A variety of limited and inefficient methods of delivering nucleic acids to keratinocytes have been demonstrated; further advances will require well-characterized reagents, rapid noninvasive assays of delivery, and well-developed skin model systems. Using intravital fluorescence and bioluminescence imaging and a standard set of reporter plasmids we demonstrate transfection of cells in mouse and human xenograft skin using intradermal injection and two microneedle array delivery systems. Reporter gene expression could be detected in individual keratinocytes, in real-time, in both mouse skin as well as human skin xenografts. These studies revealed that non-invasive intravital imaging can be used as a guide for developing gene delivery tools, establishing a benchmark for comparative testing of nucleic acid skin delivery technologies.

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Citations

Dec 3, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Guang YanHenan Li
Jan 15, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Rosalind H E ChongJames C Birchall
May 12, 2012·Advanced Drug Delivery Reviews·Yeu-Chun KimMark R Prausnitz
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Jul 1, 2015·Drug Delivery and Translational Research·Joanne McCaffreyHelen O McCarthy
Oct 24, 2013·Molecular Therapy. Nucleic Acids·Robyn P HickersonRoger L Kaspar
Sep 28, 2016·Experimental Dermatology·Sixia Huang, Panteleimon Rompolas
Jul 15, 2015·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Robyn P HickersonRoger L Kaspar
Dec 1, 2020·Journal of Pharmaceutical Sciences·Hiroshi MiyazakiKazuhiro Terai

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Methods Mentioned

BETA
xenograft
nucleic acid therapies
fluorescence imaging
confocal scanning microscopy
fluorescence microscopy
xenografts
fluorescence
electrophoresis
bioluminescence

Software Mentioned

Igor
LivingImage
ImageJ
VivaScope

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