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

通过肺部途径全身输送核酸——一种输送基因和核糖核酸的非侵入性方法

• 批准号: 2327432
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2327432
• 关键词: Systemic; delivery; nucleic; acids; via

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.

基因替代疗法和基因沉默产品已被批准用于人类，这些都是通过静脉注射或局部注射进行的。对于慢性疾病，最好通过非肠外途径给药核酸。我们假设肺给药途径可以提供一种实现基因治疗全身性暴露的方法（肺外蛋白表达）。已有报道将基因和siRNA传递到肺上皮细胞2,3，但我们的目标是在肺传递后进行全身暴露，并将探索通过非侵入性肺途径实现这一目标的方法。我们将利用新的化学物质和结构来设计非病毒载体，目的是克服与肺递送相关的挑战：肺沉积，粘膜屏障，肺上皮细胞摄取并转移到肺毛细血管，毛细血管摄取和转运到靶器官后的稳定性。