HSP70iQ435A -Encoding DNA Repigments Vitiligo Lesions in Sinclair Swine

The Journal of Investigative Dermatology
Steven W HenningI Caroline Le Poole

Abstract

Human HSP70iQ435A carries a single amino-acid modification within the dendritic cell activating region and tolerizes dendritic cells in vitro. The underlying DNA was used to prevent and treat disease in vitiligo mouse models through reduced dendritic cell activation and diminished skin T-cell infiltration, suggesting the same may be useful for patients. Physiologic differences between mouse and human skin then called for studies in large animals with human-like skin. We established the efficiency of DNA jet injection into swine skin before subcloning HSP70iQ435A into clinically suitable vector pUMVC3. Vitiligo lesions in Sinclair swine were treated with plasmid DNA to measure changes in depigmentation, T-cell infiltration, expression of HSP70i in skin, serum HSP70i, and anti-HSP70i serum titers. Remarkable repigmentation following HSP70iQ435A-encoding DNA treatment persisted throughout the 6-month follow-up period. Repigmentation was accompanied by an initial influx of T cells accompanied by increased CD4/CD8 ratios, waning by week 15. Melanocytes spanned the border of repigmenting skin, suggesting that melanocyte repopulation precedes skin melanization. Serum titer fluctuations were not treatment-associated. Importantly, treat...Continue Reading

Citations

Mar 22, 2020·Pigment Cell & Melanoma Research·Zalfa A Abdel-MalekIltefat Hamzavi
Feb 6, 2020·Annual Review of Immunology·Michael L FrisoliJohn E Harris
Sep 20, 2020·Dermatology and Therapy·Laure MigayronJulien Seneschal
Nov 18, 2020·Medicinal Research Reviews·Jianru ChenChunying Li
Nov 30, 2020·Experimental Dermatology·Jaime Piquero-CasalsLuis Puig
Dec 19, 2020·Frontiers in Immunology·Zhussipbek MukhatayevI Caroline Le Poole
Jan 7, 2021·The Journal of Dermatology·Christina Bergqvist, Khaled Ezzedine
Jan 22, 2021·Autoimmunity Reviews·Zhussipbek MukhatayevI Caroline Le Poole
Apr 17, 2021·International Journal of Pharmaceutics·Ruxuan WangJianqing Gao
May 4, 2021·Frontiers in Immunology·Katia BonifaceMeri K Tulic
Jul 21, 2021·Clinical Reviews in Allergy & Immunology·Yinghan WangChunying Li
Sep 21, 2021·Cell Stress & Chaperones·Dinesh JaishankarI Caroline Le Poole
Mar 11, 2020·Dermatology : International Journal for Clinical and Investigative Dermatology·Christina Bergqvist, Khaled Ezzedine

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