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.
摘要：
很少探索用于治疗皮肤相关疾病的基因调控疗法的研究，部分原因是全身递送效率低下。在这项研究中,瓶刷聚合物-反义寡核苷酸(ASO)缀合物，称为pacDNA，旨在靶向IL-17受体A（IL-17RA），其中涉及银屑病的发病机制。pacDNA的全身给药导致其在表皮中的积累，真皮,和老鼠皮肤的皮下，皮肤中IL-17RA基因表达降低，并显着逆转了小鼠模型中咪喹莫特（IMQ）诱导的牛皮癣的发展。这些发现突出了pacDNA作为有希望的纳米构建体用于全身性寡核苷酸递送至皮肤和用于通过全身性施用治疗牛皮癣和其他皮肤相关病症的潜力。
