Translational benefits of gene therapy to date

Gene therapy is now a reality with a number of early phase clinical trials having been completed and several currently in progress. In spite of some early setbacks substantial progress has been made with treatment of several different diseases using a variety of delivery vectors and transgenes. Indeed for some diseases gene therapy is now the treatment of choice, in particular the inherited immune deficiencies. Treatment of ocular diseases and cancer are also showing great promise. Immune responses and insertional mutagenesis still pose problems but refinement of delivery systems and an increased understanding of oncogene activation should ensure that more successful protocols will emerge in the near future. Continuous progress suggests that a wider range of diseases can be treated with gene therapy in the future.     

High Content Image Based Analysis Identifies Cell Cycle Inhibitors as Regulators of Ebola Virus Infection

Viruses modulate a number of host biological responses including the cell cycle to favor their replication. In this study, we developed a high-content imaging (HCI) assay to measure DNA content and identify different phases of the cell cycle. We then investigated the potential effects of cell cycle arrest on Ebola virus (EBOV) infection. Cells arrested in G1 phase by serum starvation or G1/S phase using aphidicolin or G2/M phase using nocodazole showed much reduced EBOV infection compared to the untreated control. Release of cells from serum starvation or aphidicolin block resulted in a time-dependent increase in the percentage of EBOV infected cells. The effect of EBOV infection on cell cycle progression was found to be cell-type dependent. Infection of asynchronous MCF-10A cells with EBOV resulted in a reduced number of cells in G2/M phase with concomitant increase of cells in G1 phase. However, these effects were not observed in HeLa or A549 cells. Together, our studies suggest that EBOV requires actively proliferating cells for efficient replication. Furthermore, multiplexing of HCI based assays to detect viral infection, cell cycle status and other phenotypic changes in a single cell population will provide useful information during screening campaigns using siRNA and small molecule therapeutics.