Institute of Molecular Medicine, Peking University, Beijing, China.
Mol Ther. 2011 Feb;19(2):381-5. doi: 10.1038/mt.2010.266. Epub 2010 Nov 30.
The elimination process of systemically administered small interfering RNA (siRNA) was investigated by using siRNA labeled with an infrared fluorescent dye. A novel siRNA elimination pathway was identified. In this pathway, liver-enriched siRNA is secreted into the gallbladder and then emptied into the intestine. Blocking this pathway resulted in the absence of siRNA fluorescence within the intestine, with greatly enhanced siRNA accumulation in liver and gallbladder at the same time. Furthermore, we demonstrated that delivery carriers play an essential role in siRNA distribution and elimination, highlighting their importance in siRNA therapeutics.
本研究采用标记有近红外荧光染料的小干扰 RNA(siRNA)来研究其在体内的消除过程。结果发现了一条新的 siRNA 消除途径:富含 siRNA 的肝胆汁排入胆囊,随后排入肠道。该途径阻断后,肠道内几乎检测不到 siRNA 荧光,而同时肝和胆囊中 siRNA 明显蓄积。此外,我们还证明了递送载体在 siRNA 的分布和消除中起着至关重要的作用,这突显了它们在 siRNA 治疗中的重要性。