%0 Journal Article
%T Selective gene silencing by viral delivery of short hairpin RNA
%A Katja Sliva
%A Barbara S Schnierle
%J Virology Journal
%D 2010
%I BioMed Central
%R 10.1186/1743-422x-7-248
%X The human genome project not only unraveled the human genetic code, but spin-off technical improvements also inspired genome sequencing of a multitude of other organisms. However, since sequence data alone are not sufficient to identify gene function, gene knock-out or knock-in strategies have to replenish the results in order to analyze the resulting phenotypic changes defining gene functions.Knowledge about the in vivo phenotype after knocking out gene products is a prerequisite to assess the therapeutic potential of inhibitors against specific targets, so in drug development knock-out animal models have become very important. However, generating transgenic animals is still very labor and cost intense. Alternatively, selective silencing can be achieved by exploiting the RNA interference (RNAi) machinery of the host cell.Since its discovery by Fire and Mello [1] in C. elegans in 1998, which gained them the Nobel prize in 2006, and by Tuschl et al. [2] in mammalian cells in 2001, RNAi was quickly adopted by the research community as a versatile tool with a wide range of applications, from reverse genetics to high throughput screening of drug targets. The key therapeutic advantage of using RNAi lies in its ability to specifically and potently knock-down the expression of disease-causing genes of known sequence.Although RNAi is in comparison to knock-out strategies, able to only knock-down the gene expression, simple in vivo inhibition of single gene products by RNAi yields phenotypes that are comparable to classical knock-out animals used for therapeutic target identification or validation. Furthermore, basic research benefits from in vivo RNAi as this strategy can be changed dependent on the desired outcome. For example, conditional gene knock-outs utilizing inducible promoters can be used to unravel molecular pathways and investigate functional genomics.RNAi is a basic pathway in eukaryotic cells. In contrast to activating cascades in cells upon exposure to long do
%U http://www.virologyj.com/content/7/1/248