以聚合物作為載體運送小型干擾核醣核酸之研究

Abstract

核醣核酸干擾(RNA interference , RNAi )是近來發展的新技術，可以用來抑制特定的基因表現。許多研究利用RNAi來抑制病毒的複製，都得到不錯的效果，使得RNAi有相當高的潛力成為新的抗病毒藥物。 目前已經找到不少運送RNAi的載體，但是大多數效果很好的載體都有毒性過高的缺點，所以本研究針對低毒性的分子來尋找可能的載體。 Pluronic 是屬於非離子性的介面活性劑，毒性不高。我們利用Pluronic類的聚合物 F68 、F108與L44來運送GAPDH siRNA，實驗結果並沒有看到GAPDH受到抑制。接著我們利用合成以共價鍵連接Pluronic F68與分子量2000Da的PEI。實驗結果顯示以Pluronic F68-PEI (2K)來運送GAPDH siRNA，有觀察到GAPDH表現受到抑制，而對照組PEI (2K)則沒觀察到GAPDH受到抑制。另外使用Pluronic F108-PEI (2K)來運送siRNA的實驗中則沒有看到GAPDH表現受到抑制。

Small interference RNA ( siRNA ) is a new technology and is able to inhibit specific gene expression. SiRNA has been used to inhibit the replication of viruses in many studies and becomes a new potential antiviral agent. Many siRNA carriers have been developed. However, the more effective the carriers are, the higher toxicity they exert. Pluronic, a non-ionic surfactant with low toxicity, is considered as a carrier candidate in this study. There was no inhibition of GAPDH expression when Pluronic F68, F108 or L44 alone was used to deliver GAPDH siRNA. The Pluronic-grafted polyethyleneimine was then synthesized. The Pluronic F68-PEI (2K) moderately delivered GAPDH siRNA into BEAS-2B cells without detectable toxicity during transfection, while free PEI (2K) didn’t show the ability to deliver siRNA.