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

Author:

Fang Yang1,Cai Jiansong1,Fei Feng1,Zhong Tongtong2,Ren Mengqi1,Wang Dali1,Li Yao3,Zhang Ke4ORCID

Affiliation:

1. Department of Chemistry and Chemical Biology Northeastern University Boston MA 02115 USA

2. Bouvé College of Health Sciences Northeastern University Boston MA 02115 USA

3. Department of Bioengineering Northeastern University Boston MA 02115 USA

4. Departments of Chemistry and Chemical Biology Chemical Engineering and Bioengineering Northeastern University Boston MA 02115 USA

Abstract

AbstractThe 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.

Funder

National Cancer Institute

National Institute of General Medical Sciences

National Science Foundation

Publisher

Wiley

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