University of Queensland Diamantina Institute, Brisbane, Australia.
Mol Ther Nucleic Acids. 2013 Jun 4;2(6):e96. doi: 10.1038/mtna.2013.22.
RNA interference (RNAi) may provide a therapeutic solution to many pulmonary epithelium diseases. However, the main barrier to the clinical use of RNAi remains the lack of efficient delivery vectors. Research has mainly concentrated on the intranasal route of delivery of short interfering RNA (siRNA) effector molecules for the treatment of respiratory diseases. However, this may be complicated in a diseased state due to the increased fluid production and tissue remodeling. Therefore, we investigated our hydration of a freeze-dried matrix (HFDM) formulated liposomes for systemic delivery to the lung epithelium. Here, we show that 45 ± 2% of epithelial murine lung cells receive siRNA delivery upon intravenous (IV) liposomal administration. Furthermore, we demonstrate that liposomal siRNA delivery resulted in targeted gene and protein knockdown throughout the lung, including lung epithelium. Taken together, this is the first description of lung epithelial delivery via cationic liposomes, and provides a proof of concept for the use of IV liposomal RNAi delivery to specifically knockdown targeted genes in the respiratory system. This approach may provide an attractive alternate therapeutic delivery strategy for the treatment of lung epithelium diseases.Molecular Therapy - Nucleic Acids (2013) 2, e96; doi:10.1038/mtna.2013.22; published online 4 June 2013.
RNA 干扰 (RNAi) 可能为许多肺上皮疾病提供治疗解决方案。然而，RNAi 临床应用的主要障碍仍然是缺乏有效的输送载体。研究主要集中在经鼻途径输送短干扰 RNA (siRNA) 效应分子治疗呼吸疾病。然而，由于液体产生增加和组织重塑，在患病状态下这可能会变得复杂。因此，我们研究了我们的冻干基质（HFDM）配方脂质体的水合作用，以用于肺上皮的系统输送。在这里，我们表明，静脉内（IV）脂质体给药后，上皮鼠肺细胞中有 45±2%接收 siRNA 递送。此外，我们证明脂质体 siRNA 递送导致靶向基因和蛋白质在整个肺部（包括肺上皮）的敲低。总之，这是首次通过阳离子脂质体描述肺上皮递送，并为使用 IV 脂质体 RNAi 递送来专门敲低呼吸系统中的靶向基因提供了概念验证。这种方法可能为肺上皮疾病的治疗提供一种有吸引力的替代治疗性递药策略。
分子治疗-核酸 (2013) 2, e96; doi:10.1038/mtna.2013.22; 在线发表 2013 年 6 月 4 日。
