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首页> 外文期刊>Journal of drug targeting >Advances in RNAi therapeutic delivery to leukocytes using lipid nanoparticles
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Advances in RNAi therapeutic delivery to leukocytes using lipid nanoparticles

机译：使用脂质纳米颗粒对rnai治疗递送至白细胞的进展

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Small interfering RNAs (siRNAs) therapeutics has advanced into clinical trials for liver diseases and solid tumors, but remain a challenge for manipulating leukocytes fate due to lack of specificity and safety issues. Leukocytes ingest pathogens and defend the body through a complex network. They are also involved in the pathogeneses of inflammation, viral infection, autoimmunity and cancers. Modulating gene expression in leukocytes using siRNAs holds great promise to treat leukocyte-mediated diseases. Leukocytes are notoriously hard to transduce with siRNAs and are spread throughout the body often located deep in tissues, therefore developing an efficient systemic delivery strategy is still a challenge. Here, we discuss recent advances in siRNA delivery to leukocyte subsets such as macrophages, monocytes, dendritic cells and lymphocytes. We focus mainly on lipid-based nanoparticles (LNPs) comprised of new generation of ionizable lipids and their ability to deliver siRNA to primary or malignant leukocytes in a targeted manner. Special emphasis is made on LNPs targeted to subsets of leukocytes and we detail a novel microfluidic mixing technology that could aid in changing the landscape of process development of LNPs from a lab tool to a potential novel therapeutic modality.
机译：小干扰RNA（SIRNA）治疗剂已经进入肝脏疾病和实体瘤的临床试验，但由于缺乏特异性和安全问题，仍然是操纵白细胞命运的挑战。白细胞摄取病原体并通过复杂的网络来保护身体。它们也参与炎症，病毒感染，自身免疫和癌症的病原因。使用SiRNA调节白细胞中的基因表达具有良好的希望治疗白细胞介导的疾病。白细胞令人惊奇地难以与siRNA脱发，并且在整个身体中涂抹经常位于组织深处，因此开发有效的系统交付策略仍然是一项挑战。在这里，我们讨论siRNA递送至白细胞亚群的最近进展，例如巨噬细胞，单核细胞，树突细胞和淋巴细胞。我们主要专注于基于脂质的纳米颗粒（LNP），包括新一代可电离脂质和它们以靶向方式将siRNA递送给初级或恶性白细胞的能力。对LNPS的特殊重点是针对白细胞亚组的LNP，我们详细介绍了一种新型微流体混合技术，可以帮助改变从实验室工具到潜在的新型治疗方式的LNP的过程开发景观。

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