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解析宿主——RNA干扰筛选如何揭示宿主与病原体的相互作用。

Illuminating the host - how RNAi screens shed light on host-pathogen interactions.

作者信息

Prudêncio Miguel, Lehmann Maik J

机构信息

Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal.

出版信息

Biotechnol J. 2009 Jun;4(6):826-37. doi: 10.1002/biot.200900071.

Abstract

Over millions of years pathogens have coevolved with their respective hosts utilizing host cell functions for survival and replication. Despite remarkable progress in developing antibiotics and vaccination strategies in the last century, infectious diseases still remain a severe threat to human health. Meanwhile, genomic research offers a new era of data-generating platforms that will dramatically enhance our knowledge of pathogens and the diseases they cause. Improvements in gene knockdown studies by RNA interference (RNAi) combined with recent developments in instrumentation and image analysis enable the use of high-throughput screening approaches to elucidate host gene functions exploited by pathogens. Although only a few RNAi-based screens focusing on host genes have been reported so far, these studies have already uncovered hundreds of genes not previously known to be involved in pathogen infection. This review describes recent progress in RNAi screening approaches, highlighting both the limitations and the tremendous potential of RNAi-based screens for the identification of essential host cell factors during infection.

摘要

在数百万年的时间里,病原体与它们各自的宿主共同进化,利用宿主细胞功能进行生存和复制。尽管在上个世纪开发抗生素和疫苗接种策略方面取得了显著进展,但传染病仍然对人类健康构成严重威胁。与此同时,基因组研究开启了一个数据生成平台的新时代,这将极大地增进我们对病原体及其所引发疾病的了解。通过RNA干扰(RNAi)改进基因敲除研究,再结合仪器和图像分析方面的最新进展,使得利用高通量筛选方法来阐明病原体所利用的宿主基因功能成为可能。尽管到目前为止仅报道了少数针对宿主基因的基于RNAi的筛选,但这些研究已经发现了数百个以前未知与病原体感染有关的基因。这篇综述描述了RNAi筛选方法的最新进展,强调了基于RNAi的筛选在识别感染过程中必需的宿主细胞因子方面的局限性和巨大潜力。

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