Nature：当RNAi遇上HIV

　　

生物通报道，今日Nature发布了一篇治疗HIV的新闻文章，该研究文章发表在Nature子刊Nature　Materials上。生物医学工程师找到了一种输送治疗性RNA到细胞的新途径，研究人员希望这一技术能用于艾滋病的局部治疗药物中。

 

来自耶鲁大学的Mark Saltzman和他的研究小组期望找到一种更好的传递siRNA的方式。研究者目前正开发携带siRNA进入阴道细胞的技术，这些siRNA具有阻断HIV复制的能力。目前传递siRNA的方式多数比较昂贵并且有毒性。Saltzman希望开发一种廉价无毒的传递系统。

 

令Saltzman惊奇的是，目前已经被美国FDA批准的一种医用塑料是最佳的选择，这种塑料可生物降解，并且具有良好的生物可容性。Saltzman将数以千计的siRNA装进纳米级的塑料颗粒中，再将这些颗粒融合到阴道凝胶剂中，妇女使用了这种凝胶就能阻止HIV入侵，免受感染。

 

研究小组在小鼠模型上进行动物实验，他们所用的转基因小鼠的阴道细胞能表达GFP蛋白，研究人员将阻断GFP表达的siRNA包裹在纳米塑料颗粒中，再倒入雌性小鼠的阴道，能有效的抑制阴道细胞表达GFP，这些实验结果证实，这种传递方式能有效的发挥生物功效，阻断GFP。

（生物通 小茜）

生物通推荐原文检索：Intravaginal gene silencing using biodegradable polymer nanoparticles densely loaded with small-interfering RNA

【Abstract】

Vaginal instillation of small-interfering RNA (siRNA) using liposomes has led to silencing of endogenous genes in the genital tract and protection against challenge from infectious disease. Although siRNA lipoplexes are easily formulated, several of the most effective transfection agents available commercially may be toxic to the mucosal epithelia and none are able to provide controlled or sustained release. Here, we demonstrate an alternative approach using nanoparticles composed entirely of FDA-approved materials. To render these materials effective for gene silencing, we developed novel approaches to load them with high amounts of siRNA. A single dose of siRNA-loaded nanoparticles to the mouse female reproductive tract caused efficient and sustained gene silencing. Knockdown of gene expression was observed proximal (in the vaginal lumen) and distal (in the uterine horns) to the site of topical delivery. In addition, nanoparticles penetrated deep into the epithelial tissue. This is the first report demonstrating that biodegradable polymer nanoparticles are effective delivery vehicles for siRNA to the vaginal mucosa.