靶向皮肤：在银屑病小鼠模型中研究瓶刷聚合物-反义寡核苷酸缀合物。
Targeting the Skin: The Study of a Bottlebrush Polymer-Antisense Oligonucleotide Conjugate in a Psoriasis Mouse Model.
机构信息
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA.
Bouvé College of Health Sciences, Northeastern University, Boston, MA, 02115, USA.
出版信息
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。
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