Advanced materials (Deerfield Beach, Fla.)Oct 14, 2026

Local mRNA Treatments Delivered to Accessible Body Areas for Targeting Diseases

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 15, 2026

Abstract

Anatomically Accessible Local mRNA Therapeutics (ALmT) focuses on delivering mRNA directly to affected tissues instead of relying on systemic circulation.

ALmT aims for localized mRNA expression, which is crucial for treating diseases confined to specific tissues.
Efficacy of ALmT is primarily derived from the local biological activity of the protein produced rather than systemic effects.
The review categorizes barriers and engineering strategies for mRNA delivery across various anatomical sites.
Applications of ALmT include protein restoration, cytokine or growth-factor supplementation, local antibody-fragment production, and tissue repair.
Design principles and quantitative evaluations are discussed to support the clinical translation of mRNA therapies targeting localized diseases.

Simplified

Messenger RNA (mRNA) therapeutics have expanded from clinically validated prophylactic vaccines toward protein replacement and supplementation. Yet mRNA delivery remains centered on intramuscular vaccination and intravenous administration, largely optimized for systemic adaptive immunity or circulation-mediated biodistribution. Many localized diseases, however, are confined to tissues or compartments accessible by topical, transdermal, inhaled, oral, catheter-based, ocular, or intra-articular administration without initial reliance on circulation. For these diseases, the therapeutic objective is likewise local: therapeutically relevant mRNA expression occurs within the affected tissue, and efficacy derives predominantly from the local biological activity of the encoded protein rather than from downstream systemic effects initiated by local expression. This therapeutic paradigm is defined here as Anatomically Accessible Local mRNA Therapeutics (ALmT). The review first distinguishes ALmT from intravenous mRNA delivery and intramuscular mRNA vaccination, then organizes site-specific barriers and engineering strategies across major anatomical sites. It further examines disease-focused ALmT applications, highlighting protein restoration, cytokine or growth-factor supplementation, local antibody-fragment production, regenerative modulation, and tissue repair. Finally, it discusses general design principles, quantitative PK/PD evaluation, repeat-dose safety, and clinical translation. Overall, the ALmT framework may facilitate the design, quantitative evaluation, and clinical translation of mRNA therapies for localized diseases.

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Local mRNA Treatments Delivered to Accessible Body Areas for Targeting Diseases

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