Genes that when inactivated result in cell death or enhanced cell growth, respectively are defined as lethal and rescuer genes. The ability to identify these genes in large-scale automated screening campaigns could lead to the discovery of valuable new drug targets.
A genome-wide lethality screen that relies on RNA interference technology and led to the validation of 239 gene candidates essential for cell survival is described in ASSAY and Drug Development Technologies
, a peer-reviewed journal published from Mary Ann Liebert, Inc., publishers. The article is available free on the ASSAY and Drug Development Technologies
A team of researchers led by Bhavneet Bhinder and Hakim Djaballah, Memorial Sloan-Kettering Cancer Center, New York, NY, present their work in the article "An Arrayed Genome-Scale Lentiviral-Enabled Short Hairpin RNA Screen Identifies Lethal and Rescuer Gene Candidates."
The authors developed a high-stringency analysis method used to determine which genes result in cell death when they are "knocked down." Gene knockdown is achieved via an RNA interference approach, using double-stranded RNA molecules called short hairpin RNAs, or shRNAs. A shRNA binds to a target gene, blocking gene expression. The high-throughput screen is carried out in cells in 384-well microtiter plates.