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A tumor-selective mRNA system enables precision cancer treatment.

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Molecular therapy : the journal of the American Society of Gene Therapy 📖 저널 OA 84.1% 2024: 1/1 OA 2025: 22/22 OA 2026: 35/46 OA 2024~2026 2026 Vol.34(2) p. 1066-1083 OA
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Żak MM, Yoo J, Utrero-Rico A, Walter W, Mainkar G, Adjmi M

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mRNA has revolutionized vaccine development, demonstrating high efficacy and safety in COVID-19 vaccines, and is now being explored for broader therapeutic applications.

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APA Żak MM, Yoo J, et al. (2026). A tumor-selective mRNA system enables precision cancer treatment.. Molecular therapy : the journal of the American Society of Gene Therapy, 34(2), 1066-1083. https://doi.org/10.1016/j.ymthe.2025.11.015
MLA Żak MM, et al.. "A tumor-selective mRNA system enables precision cancer treatment.." Molecular therapy : the journal of the American Society of Gene Therapy, vol. 34, no. 2, 2026, pp. 1066-1083.
PMID 41243282 ↗

Abstract

mRNA has revolutionized vaccine development, demonstrating high efficacy and safety in COVID-19 vaccines, and is now being explored for broader therapeutic applications. However, while vaccines rely on widespread antigen expression, many therapeutic strategies-particularly in oncology-require precise, cell-selective gene expression. Here, we present the selective modified RNA translation system (SMRTS), a versatile, engineered mRNA system that enables targeted gene expression in specific cell populations. As a proof of concept, we developed cancer-specific variants, bcSMRTS and ccSMRTS, for breast and colon cancer, respectively. Systemic delivery of lipid nanoparticle (LNP)-encapsulated SMRTS constructs yielded a 114-fold and 141-fold increase in tumor-specific expression in 4T1 and MC-38 models, respectively, while reducing off-target expression by over 380-fold. Therapeutic deployment of Pten ccSMRTS suppressed tumor growth by 45%, and combination with modRNA-derived anti-checkpoint inhibitor antibodies (modRNabs) resulted in up to 93% tumor inhibition. Beyond oncology, SMRTS introduces a novel mRNA tool, providing a versatile system for cell-selective gene expression. By expanding the mRNA therapeutics toolbox, SMRTS paves the way for precise mRNA-based interventions across a wide range of disease settings.

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