dc.contributor.author | Lenn, Jon D | |
dc.contributor.author | Neil, Jessica | |
dc.contributor.author | Donahue, Christine | |
dc.contributor.author | Demock, Kellie | |
dc.contributor.author | Tibbetts, Caitlin Vestal | |
dc.contributor.author | Cote-Sierra, Javier | |
dc.contributor.author | Smith, Susan H | |
dc.contributor.author | Rubenstein, David | |
dc.contributor.author | Therrien, Jean-Philippe | |
dc.contributor.author | Pendergrast, P Shannon | |
dc.contributor.author | Killough, Jason | |
dc.contributor.author | Brown, Marc B | |
dc.contributor.author | Williams, Adrian C | |
dc.date.accessioned | 2018-02-28T17:04:11Z | |
dc.date.available | 2018-02-28T17:04:11Z | |
dc.date.issued | 2018-02-01 | |
dc.identifier.citation | Lenn , J D , Neil , J , Donahue , C , Demock , K , Tibbetts , C V , Cote-Sierra , J , Smith , S H , Rubenstein , D , Therrien , J-P , Pendergrast , P S , Killough , J , Brown , M B & Williams , A C 2018 , ' RNA Aptamer Delivery through Intact Human Skin ' , Journal of Investigative Dermatology , vol. 138 , no. 2 , pp. 282-290 . https://doi.org/10.1016/j.jid.2017.07.851 | |
dc.identifier.issn | 0022-202X | |
dc.identifier.uri | http://hdl.handle.net/2299/19838 | |
dc.description | This document is the Accepted Manuscript of the following article: Jon D. Lenn, et al, ‘RNA Aptamer Delivery through Intact Human Skin’, Journal of Investigative Dermatology, Vol. 138 (2): 282-290, February 2018. Under embargo until 20 September 2018. The final, published version is available online at DOI: https://doi.org/10.1016/j.jid.2017.07.851. | |
dc.description.abstract | It is generally recognized that only relatively small molecular weight (typically < ∼ 500 Da) drugs can effectively permeate through intact stratum corneum. Here, we challenge this orthodoxy using a 62-nucleotide (molecular weight = 20,395 Da) RNA-based aptamer, highly specific to the human IL-23 cytokine, with picomolar activity. Results demonstrate penetration of the aptamer into freshly excised human skin using two different fluorescent labels. A dual hybridization assay quantified aptamer from the epidermis and dermis, giving levels far exceeding the cellular half maximal inhibitory concentration values (>100,000-fold), and aptamer integrity was confirmed using an oligonucleotide precipitation assay. A T helper 17 response was stimulated in freshly excised human skin resulting in significantly upregulated IL-17f, and IL-22; topical application of the IL-23 aptamer decreased both IL-17f and IL-22 by approximately 45% but did not result in significant changes to IL-23 mRNA levels, confirming that the aptamer did not globally suppress mRNA levels. This study demonstrates that very-large-molecular-weight RNA aptamers can permeate across the intact human skin barrier to therapeutically relevant levels into both the epidermis and dermis and that the skin-penetrating aptamer retains its biologically active conformational structure capable of binding to endogenous IL-23. | en |
dc.format.extent | 9 | |
dc.format.extent | 3010234 | |
dc.language.iso | eng | |
dc.relation.ispartof | Journal of Investigative Dermatology | |
dc.subject | Biochemistry | |
dc.subject | Molecular Biology | |
dc.subject | Dermatology | |
dc.subject | Cell Biology | |
dc.title | RNA Aptamer Delivery through Intact Human Skin | en |
dc.contributor.institution | Centre for Research into Topical Drug Delivery and Toxicology | |
dc.description.status | Peer reviewed | |
dc.date.embargoedUntil | 2018-12-12 | |
dc.identifier.url | http://www.scopus.com/inward/record.url?scp=85041662034&partnerID=8YFLogxK | |
rioxxterms.versionofrecord | 10.1016/j.jid.2017.07.851 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |