Systemic delivery of nucleic acids via the pulmonary route - a non-invasive method of delivering genes and ribonucleic acids

基因替代疗法和基因沉默产品已被批准用于人类1，这些产品通过静脉或局部注射给予。对于慢性疾病，最好通过非肠外途径给药。我们假设，肺部给药途径可以提供一种全身暴露于基因疗法(肺外蛋白质表达)的方法。已经报道了将基因和siRNA输送到肺上皮细胞2，3，然而，我们的目标是在肺部输送后全身暴露，并将探索通过非侵入性肺途径实现这一目标的方法。我们将设计利用新的化学和构建的非病毒载体，目的是克服与肺部递送相关的挑战：肺沉积、粘膜屏障、肺上皮细胞摄取并转移到肺毛细血管、毛细血管摄取和移位到靶器官后的稳定性。

Gene replacement therapy and gene silencing products have been approved for use in humans1and these are administered by intravenous or local injections . For chronic conditions it would bepreferable to administer nucleic acids by non-parenteral routes. We hypothesise that the pulmonary route of administration could provide a means of achieving systemic exposure to gene therapeutics (protein expression outside of the lung). The delivery of genes and siRNA to the lung epithelial cells has been reported2, 3, however we are aiming for systemic exposure following pulmonary delivery and will explore ways in which this may be achieved via the non-invasive pulmonary route. We will design non-viral vectors utilising new chemistries and constructs with the aim of overcoming the challenges associated with pulmonary delivery: lung deposition, the mucosal barrier, uptake by lung epithelial cells and transfer to pulmonary capillaries, stability following capillary uptake and translocation to target organs.