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. 2025 Jan:123:903-913.
doi: 10.1016/j.bbi.2024.10.031. Epub 2024 Nov 1.

An initial investigation of transcutaneous delivery of plasmid DNA encoding interleukin-10 for the treatment of psoriatic skin conditions

Igor Rafael Correia Rocha  1 , Maggie R Finch  1 , Jayson B Ball  1 , Michael E Harland  1 , Madison Clements  1 , Suzanne Green-Fulgham  1 , Guiyun Song  2 , Yi Liu  2 , Daniel Banov  2 , Linda R Watkins  3
Affiliations

An initial investigation of transcutaneous delivery of plasmid DNA encoding interleukin-10 for the treatment of psoriatic skin conditions

Igor Rafael Correia Rocha et al. Brain Behav Immun. 2025 Jan.

Abstract

Psoriasis is a chronic immune-mediated skin disorder characterized by intense local inflammation, epidermal hyperplasia, and leukocyte infiltration. Current treatment approaches for psoriasis aim to alleviate symptoms and prevent disease progression, including systemically administered drugs with whole body side effects. Despite some advances in psoriasis treatment, success has been quite limited. To begin to address this challenge, we undertook an initial investigation of whether transcutaneous delivery of an endogenous anti-inflammatory cytokine could provide an effective, local treatment of psoriatic-like skin conditions. To do this, we utilized a previously documented rodent model of psoriasis, induced via a single topical application of Imiquimod (IMQ) to the shaved back of rats. The therapeutic approach used for this initial investigation was delivery of plasmid DNA encoding rat interleukin-10 (pDNA-rIL10), a non-viral gene therapy approach previously shown to be effective in suppressing neuroinflammatory disorders after localized delivery either intracerebrally or intrathecally. Translation of this CNS therapeutic for use in psoriatic-like skin disorders required reformulation to enable transcutaneous delivery. Toward that end, pDNA-rIL10 was topically applied in Lipoderm HMW, a base explicitly designed to deliver higher molecular weight compounds into skin. Here we show that a single topical application of pDNA-rIL10 in Lipoderm HMW was effective in decreasing mRNA levels of pro-inflammatory cytokines as well as reducing the recruitment of T-cells to IMQ-treated skin. Furthermore, this transcutaneous IL-10 gene therapy decreased signs of skin inflammation, reflected by reduced erythema. Moreover, the results provide an initial indication that IL10 may stimulate hair regrowth in psoriatic-like skin.

Keywords: Cytokines; D-Mannose; Gene therapy; Imiquimod; Lipoderm HMW; Psoriasis; Rat; T-cells.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Linda Watkins is a scientific co-founder of Xalud Therapeutics and Vetana Animal Health that are pursuing the use of this pDNA IL-10 gene therapy approach in clinical trials of osteoarthritis and like indications. Daniel Banov is an inventor of Lipoderm HMW and he, Guiyun Song, and Yi Liu are employees of PCCA.].

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