用短干涉RNA（siRNA）進(jìn)行的基因沉默的治療潛力是巨大的——在理論上是這樣,。在實(shí)踐上，要使它成為一種實(shí)用方法還需要克服很多障礙,，而其中的障礙之一是,，怎樣將siRNA安全輸送到其目標(biāo)組織,。
本期Nature介紹的一個(gè)新的輸送體系,，可能會(huì)被證明是朝實(shí)現(xiàn)這一目標(biāo)所邁出的重要一步。設(shè)計(jì)用來(lái)在使巨噬細(xì)胞中MAP4k4酶的表達(dá)沉默的siRNA,，被封裝在微米尺度的beta1,3-D-葡聚糖中,，以口服方式給小鼠施用。所封裝的siRNA可增加患有脂多糖誘導(dǎo)的炎癥（炎癥疾病的一個(gè)常見模型）的小鼠存活率,，同時(shí)抑制全身性炎癥,。這種方法在活體中的功效要比以前所報(bào)告的用系統(tǒng)給藥法輸送siRNA的方式強(qiáng)250倍。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 458, 1180-1184 (30 April 2009) | doi:10.1038/nature07774
Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation
Myriam Aouadi1,2, Gregory J. Tesz1,2, Sarah M. Nicoloro1, Mengxi Wang1, My Chouinard1, Ernesto Soto1, Gary R. Ostroff1 & Michael P. Czech1
1 Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
2 These authors contributed equally to this work.
Gene silencing by double-stranded RNA, denoted RNA interference, represents a new paradigm for rational drug design1. However, the transformative therapeutic potential of short interfering RNA (siRNA) has been stymied by a key obstacle—safe delivery to specified target cells in vivo 2. Macrophages are particularly attractive targets for RNA interference therapy because they promote pathogenic inflammatory responses in diseases such as rheumatoid arthritis, atherosclerosis, inflammatory bowel disease and diabetes3. Here we report the engineering of 1,3-d-glucan-encapsulated siRNA particles (GeRPs) as efficient oral delivery vehicles that potently silence genes in mouse macrophages in vitro and in vivo. Oral gavage of mice with GeRPs containing as little as 20 g kg-1 siRNA directed against tumour necrosis factor (Tnf-) depleted its messenger RNA in macrophages recovered from the peritoneum, spleen, liver and lung, and lowered serum Tnf- levels. Screening with GeRPs for inflammation genes revealed that the mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) is a previously unknown mediator of cytokine expression. Importantly, silencing Map4k4 in macrophages in vivo protected mice from lipopolysaccharide-induced lethality by inhibiting Tnf- and interleukin-1production. This technology defines a new strategy for oral delivery of siRNA to attenuate inflammatory responses in human disease.
