University of Hertfordshire

From the same journal

RNA Aptamer Delivery through Intact Human Skin

Research output: Contribution to journalArticlepeer-review

Standard

RNA Aptamer Delivery through Intact Human Skin. / Lenn, Jon D; Neil, Jessica; Donahue, Christine; Demock, Kellie; Tibbetts, Caitlin Vestal; Cote-Sierra, Javier; Smith, Susan H; Rubenstein, David; Therrien, Jean-Philippe; Pendergrast, P Shannon; Killough, Jason; Brown, Marc B; Williams, Adrian C.

In: Journal of Investigative Dermatology, Vol. 138, No. 2, 01.02.2018, p. 282-290.

Research output: Contribution to journalArticlepeer-review

Harvard

Lenn, JD, Neil, J, Donahue, C, Demock, K, Tibbetts, CV, Cote-Sierra, J, Smith, SH, Rubenstein, D, Therrien, J-P, Pendergrast, PS, Killough, J, Brown, MB & Williams, AC 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

APA

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, 138(2), 282-290. https://doi.org/10.1016/j.jid.2017.07.851

Vancouver

Lenn JD, Neil J, Donahue C, Demock K, Tibbetts CV, Cote-Sierra J et al. RNA Aptamer Delivery through Intact Human Skin. Journal of Investigative Dermatology. 2018 Feb 1;138(2):282-290. https://doi.org/10.1016/j.jid.2017.07.851

Author

Lenn, Jon D ; Neil, Jessica ; Donahue, Christine ; Demock, Kellie ; Tibbetts, Caitlin Vestal ; Cote-Sierra, Javier ; Smith, Susan H ; Rubenstein, David ; Therrien, Jean-Philippe ; Pendergrast, P Shannon ; Killough, Jason ; Brown, Marc B ; Williams, Adrian C. / RNA Aptamer Delivery through Intact Human Skin. In: Journal of Investigative Dermatology. 2018 ; Vol. 138, No. 2. pp. 282-290.

Bibtex

@article{afa2c145c2924cd39ec08b2846261937,
title = "RNA Aptamer Delivery through Intact Human Skin",
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.",
author = "Lenn, {Jon D} and Jessica Neil and Christine Donahue and Kellie Demock and Tibbetts, {Caitlin Vestal} and Javier Cote-Sierra and Smith, {Susan H} and David Rubenstein and Jean-Philippe Therrien and Pendergrast, {P Shannon} and Jason Killough and Brown, {Marc B} and Williams, {Adrian C}",
note = "This document is the Accepted Manuscript of the following article: Jon D. Lenn, et al, {\textquoteleft}RNA Aptamer Delivery through Intact Human Skin{\textquoteright}, 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. ",
year = "2018",
month = feb,
day = "1",
doi = "10.1016/j.jid.2017.07.851",
language = "English",
volume = "138",
pages = "282--290",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "2",

}

RIS

TY - JOUR

T1 - RNA Aptamer Delivery through Intact Human Skin

AU - Lenn, Jon D

AU - Neil, Jessica

AU - Donahue, Christine

AU - Demock, Kellie

AU - Tibbetts, Caitlin Vestal

AU - Cote-Sierra, Javier

AU - Smith, Susan H

AU - Rubenstein, David

AU - Therrien, Jean-Philippe

AU - Pendergrast, P Shannon

AU - Killough, Jason

AU - Brown, Marc B

AU - Williams, Adrian C

N1 - 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.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85041662034&partnerID=8YFLogxK

U2 - 10.1016/j.jid.2017.07.851

DO - 10.1016/j.jid.2017.07.851

M3 - Article

C2 - 28942363

VL - 138

SP - 282

EP - 290

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 2

ER -