ArticleCureus2026
Synergistic Enhancement of Non-viral SIRT1 Gene Delivery to Human Skin Equivalents Using Microneedling and Liposomal Vectors.
Article in Cureus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors.
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Abstract
introductionThe "longevity gene" sirtuin 1 (SIRT1) is a critical regulator of oxidative stress and cellular senescence, making it a high-value target for anti-aging dermatological interventions. However, the stratum corneum poses a formidable barrier to the transdermal delivery of therapeutic genes. This study systematically evaluated the efficacy of non-viral SIRT1 plasmid delivery to a full-thickness 3D human skin equivalent (T-Skin™) using distinct vector formulations and physical enhancement methods. MATERIALS AND
methodsWe compared the delivery efficiency of naked plasmid DNA and a cationic liposomal formulation using two delivery methods: (1) simple topical application and (2) automated microneedling (Dermapen, 0.2 mm diameter). SIRT1 expression was quantified 24 hours post-delivery using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and validated by immunohistochemistry (IHC).
resultsThe results demonstrated a pronounced synergistic effect: the combination of a liposomal plasmid with Dermapen (Lipo-Dermapen) yielded the highest efficiency, with a ~357-fold increase in SIRT1 mRNA expression compared with the control. Notably, the second-highest efficiency was achieved by the simple, non-invasive, and topical application of naked plasmids (Plasmid-Direct), which achieved a remarkable ~70-fold increase in expression. This non-invasive approach unexpectedly outperformed other delivery groups, including liposomal topical application (Lipo-Direct, ~27-fold) and naked plasmid with Dermapen (Plasmid-Dermapen, ~10-fold).
conclusionsThe Lipo-Dermapen platform provides robust proof of concept for the development of high-efficacy, minimally invasive clinical gene therapies. Furthermore, the unexpected efficacy of non-invasive naked plasmid delivery suggests a novel potential for accessible, self-administered dermatological interventions.
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