Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles
Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles
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DOI：
10.1016/j.ymthe.2018.03.019
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发表时间：
2018-06-06
影响因子：
12.4
通讯作者：
Khvorova, Anastasia
中科院分区：
文献类型：
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作者：
Biscans, Annabelle;Haraszti, Reka A.;Khvorova, Anastasia
小的细胞外囊泡（sev）显示出作为递送治疗性RNA的天然纳米装置的希望，但有效装载治疗性RNA仍然是一个挑战。我们最近的研究表明，胆固醇附着在小干扰rna （sirna）上，可以有效和高效地装载到sev中。在这里，我们系统地探索了脂质偶联物——脂肪酸、甾醇和维生素——将sirna装载到sev中并支持初级神经元中基因沉默的能力。共轭sirna的疏水性决定了sirna - sev复合物的负载效率和沉默活性。维生素e偶联的siRNA支持最佳的sev装载和高效的RNA传递到神经元。
Small extracellular vesicles (sEVs) show promise as natural nano-devices for delivery of therapeutic RNA, but efficient loading of therapeutic RNA remains a challenge. We have recently shown that the attachment of cholesterol to small interfering RNAs (siRNAs) enables efficient and productive loading into sEVs. Here, we systematically explore the ability of lipid conjugates-fatty acids, sterols, and vitamins-to load siRNAs into sEVs and support gene silencing in primary neurons. Hydrophobicity of the conjugated siRNAs defined loading efficiency and the silencing activity of siRNA-sEVs complexes. Vitamin-E-conjugated siRNA supported the best loading into sEVs and productive RNA delivery to neurons.