Targeting the Skin: The Study of a Bottlebrush Polymer‐Antisense Oligonucleotide Conjugate in a Psoriasis Mouse Model

Abstract The investigation of gene regulation therapeutics for the treatment of skin‐related diseases is rarely explored in part due to inefficient systemic delivery. In this study, a bottlebrush polymer‐antisense oligonucleotide (ASO) conjugate, termed pacDNA, designed to target IL‐17 receptor A (IL‐17RA), which is involved in psoriasis pathogenesis is presented. Systemic administration of pacDNA led to its accumulation in epidermis, dermis, and hypodermis of mouse skin, reduced IL‐17RA gene expression in skin, and significantly reversed the development of imiquimod (IMQ)‐induced psoriasis in a mouse model. These findings highlight the potential of the pacDNA as a promising nanoconstruct for systemic oligonucleotide delivery to the skin and for treating psoriasis and other skin‐related disorders through systemic administration.