Targeting the IL-17 Receptor Using Liposomal Spherical Nucleic Acids as Topical Therapy for Psoriasis

Area of Science:

• Dermatology
• Nanotechnology
• Molecular Biology

Background:

• T helper 17 (Th17) signaling is crucial in psoriasis development.
• Systemic IL-17 inhibitors are effective but have limitations.
• Novel topical delivery systems are needed for targeted gene regulation in skin.

Purpose of the Study:

• To develop and evaluate topical gene-regulating nanoconstructs (L-SNAs) for psoriasis treatment.
• To assess the efficacy of L-SNAs targeting the IL-17 receptor in preclinical models.
• To investigate the potential of topical IL-17 receptor suppression as a psoriasis therapy.

Main Methods:

• Generation of liposomal spherical nucleic acids (L-SNAs) carrying antisense DNA.
• Topical application of L-SNAs targeting the mouse Il17ra gene in imiquimod-induced psoriasis-like mouse model.
• Evaluation of clinical, histological, and transcriptional changes, including gene and protein expression.
• Testing of human IL17RA L-SNAs in 3D skin cultures and human explants.

Main Results:

• Topical Il17ra L-SNAs significantly reversed psoriasis development in mice, reducing modified PASI by 74% and epidermal thickness by 56%.
• L-SNAs decreased Il17ra protein by 75% and key psoriasis marker gene expression.
• Human IL17RA L-SNAs effectively knocked down IL17RA mRNA in 3D cultures and explants, and reduced IL-17-induced genes in psoriatic skin rafts.

Conclusions:

• Targeted topical suppression of IL-17 receptor A (IL17RA) using L-SNAs is a viable therapeutic strategy for psoriasis.
• L-SNAs demonstrate efficient skin penetration and gene knockdown capabilities.
• This approach represents a promising advancement in topical psoriasis treatment.