用短干涉RNA（siRNA）进行的基因沉默的治疗潜力是巨大的——在理论上是这样。在实践上，要使它成为一种实用方法还需要克服很多障碍，而其中的障碍之一是，怎样将siRNA安全输送到其目标组织。
本期Nature介绍的一个新的输送体系，可能会被证明是朝实现这一目标所迈出的重要一步。设计用来在使巨噬细胞中MAP4k4酶的表达沉默的siRNA，被封装在微米尺度的beta1,3-D-葡聚糖中，以口服方式给小鼠施用。所封装的siRNA可增加患有脂多糖诱导的炎症（炎症疾病的一个常见模型）的小鼠存活率，同时抑制全身性炎症。这种方法在活体中的功效要比以前所报告的用系统给药法输送siRNA的方式强250倍。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
