Therapeutic alteration of gene expression in vivo can be achieved by delivering nucleic acids (e.g., mRNA, siRNA) using nanoparticles. Recent progress in modified messenger RNA (mmRNA) synthesis facilitated the development of lipid nanoparticles (LNPs) loaded with mmRNA as a promising tool for in vivo protein expression. Although progress have been made with mmRNA-LNPs based protein expression in hepatocytes, cell specificity is still a major challenge. Moreover, selective protein expression is essential for an improved therapeutic effect, due to the heterogeneous nature of diseases. Here, we present a precision protein expression strategy in Ly6c⁺ inflammatory leukocytes in inflammatory bowel disease (IBD) induced mice. We demonstrate a therapeutic effect in an IBD model by targeted expression of the interleukin 10 in Ly6c⁺ inflammatory leukocytes. A selective mmRNA expression strategy has tremendous therapeutic potential in IBD and can ultimately become a novel therapeutic modality in many other diseases.

中文翻译：

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修饰的表达治疗性mRNA的细胞向白细胞的细胞特异性传递。

体内基因表达的治疗性改变可通过使用纳米颗粒递送核酸（例如，mRNA，siRNA）来实现。修饰信使RNA（mmRNA）合成的最新进展促进了装载有mmRNA作为体内蛋白表达的有前途工具的脂质纳米颗粒（LNP）的发展。尽管基于mmRNA-LNPs的蛋白在肝细胞中的表达已取得进展，但细胞特异性仍是一个主要挑战。此外，由于疾病的异质性，选择性蛋白表达对于改善治疗效果必不可少。在这里，我们提出了Ly6c ^+中的精确蛋白质表达策略炎症性肠病（IBD）诱导的小鼠中的炎症性白细胞。我们通过在Ly6c ⁺炎症性白细胞中靶向表达白介素10在IBD模型中证明了治疗效果。选择性mmRNA表达策略在IBD中具有巨大的治疗潜力，最终可以成为许多其他疾病的新型治疗手段。