A virus-based method that screens for chemical or genetically-encoded inhibitors of ion channels is described online in Nature Methods.
Ion channels are cell membrane-spanning proteins that, when activated, allow the influx of ions. They encompass a large family of over 400 proteins and play key roles in maintaining cellular function. While blocking their activity has proven useful for certain medical applications, these drugs usually elicit severe side effects due to their wide range action and lack of selectivity for the intended cell alone.
Joseph Glorioso and colleagues wanted to find more specific channel modulators and set up a virus-based screen in which the virus level is an indicator for inhibitor efficacy. They reasoned that overexpression of an ion channel in cells via a virus would be detrimental to the cell and consequently impede viral replication; while the presence of an inhibitor of channel function would keep the cells healthy and allow replication. The advance over other screens for channel inhibitors is that the technique can easily be adapted to screen for genetically-encoded inhibitors by coinfection of a second virus that encodes the inhibitor. The inhibitor's DNA can then be easily retrieved from the viral genome.
This method can easily be scaled up to screen whole DNA libraries that express a wide range of potential channel modulators. These genetically encoded inhibitors will help reveal the biology behind channel regulation and are likely to lead to more specific inhibitors.
Joseph Glorioso (University of Pittsburgh School of Medicine, PA, USA)
(C) Nature Methods press release.
Message posted by: Trevor M. D'Souza