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Peer-reviewed veterinary case report

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

Journal:
Small (Weinheim an der Bergstrasse, Germany)
Year:
2024
Authors:
Fang, Yang et al.
Affiliation:
Department of Chemistry and Chemical Biology · United States

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.

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Original publication: https://pubmed.ncbi.nlm.nih.gov/39140277/