Atopic dermatitis (AD) is a common chronic inflammatory skin disorder affecting all age groups, especially children, with a prevalence of up to 20% globally. AD remains burdensome and incurable with current therapeutic strategies—ranging from trigger avoidance and skincare to medication—primarily address symptoms rather than disease modification, underscoring the imperative for innovative therapeutic paradigms. RNA-targeted therapies, particularly antisense molecules, have emerged as a transformative approach in precision medicine, with proven clinical success in diseases such as spinal muscular atrophy and familial chylomicronemia syndrome. These therapeutics achieve post-transcriptional regulation unattainable by conventional therapies, enabling direct targeting of messenger RNA (mRNA) and regulatory non-coding RNAs (ncRNAs) implicated in disease pathogenesis. Furthermore, skin is better suited to the antisense modulation due to the relatively easy access to target cells. Numerous studies have explored antisense-based targeting of key drivers in AD progression, yielding promising proof-of-concept results and prompting several early-stage clinical trials. This modality represents a paradigm shift in AD management—one that aligns with the broader revolution in RNA therapeutics reshaping modern medicine. This review critically examines the evolving role of antisense technology in AD, addressing both its mechanistic rationale and the translational challenges that must be overcome to realize its full clinical potential.
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