Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA.
Bouvé College of Health Sciences, Northeastern University, Boston, MA, 02115, USA.
Small. 2024 Nov;20(47):e2403949. doi: 10.1002/smll.202403949. Epub 2024 Aug 14.
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.
由于系统递送效率低下，用于治疗皮肤相关疾病的基因调控治疗的研究很少。本研究设计了一种靶向白细胞介素 17 受体 A（IL-17RA）的梳状聚合物-反义寡核苷酸（ASO）缀合物，称为 pacDNA，该基因参与银屑病的发病机制。pacDNA 的系统给药导致其在小鼠皮肤的表皮、真皮和皮下组织中积累，降低了皮肤中 IL-17RA 基因的表达，并显著逆转了咪喹莫特（IMQ）诱导的银屑病在小鼠模型中的发展。这些发现突出了 pacDNA 作为一种有前途的纳米结构用于将寡核苷酸系统递送至皮肤，并通过全身给药治疗银屑病和其他皮肤相关疾病的潜力。
