The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.
Department of the Orthopedics of Traditional Chinese Medicine (TCM), the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Front Immunol. 2023 Feb 8;14:1109381. doi: 10.3389/fimmu.2023.1109381. eCollection 2023.
Despite the protection and management of skin has been paid more and more attention, effective countermeasures are still lacking for patients suffering from UV or chemotherapy with damaged skin. Recently, gene therapy by small interfering RNA (siRNA) has emerged as a new therapeutic strategy for skin lesions. However, siRNA therapy has not been applied to skin therapy due to lack of effective delivery vector.
Here, we develop a synthetic biology strategy that integrates the exosomes with artificial genetic circuits to reprogram the adipose mesenchymal stem cell to express and assemble siRNAs into exosomes and facilitate in vivo delivery siRNAs for therapy of mouse models of skin lesions.
Particularly, siRNA enriched exosomes (si-ADMSC-EXOs) could be directly taken up by the skin cells to inhibit the expression of skin injury related genes. When mice with skin lesions were smeared with si-ADMSC-EXOs, the repair of lesioned skin became faster and the expression of inflammatory cytokines were decreased.
Overall, this study establishes a feasible therapeutic strategy for skin injury, which may offer an alternative to conventional biological therapies requiring two or more independent compounds.
尽管人们越来越重视皮肤的保护和管理，但对于因紫外线或化疗而受损皮肤的患者，仍缺乏有效的应对措施。最近，小干扰 RNA（siRNA）的基因治疗已成为皮肤损伤的一种新的治疗策略。然而，由于缺乏有效的传递载体，siRNA 治疗尚未应用于皮肤治疗。
在这里，我们开发了一种合成生物学策略，将外泌体与人工遗传电路集成，使脂肪间充质干细胞表达并将 siRNA 组装成外泌体，并促进 siRNA 在体内的递送来治疗皮肤损伤的小鼠模型。
特别地，富含 siRNA 的外泌体（si-ADMSC-EXOs）可以被皮肤细胞直接摄取，从而抑制与皮肤损伤相关的基因表达。当涂抹有皮肤损伤的小鼠时，受损皮肤的修复速度更快，炎症细胞因子的表达也降低了。
总的来说，本研究为皮肤损伤建立了一种可行的治疗策略，这可能为需要两种或更多独立化合物的传统生物治疗提供替代方案。
