The RNA drug revolution -- a new approach to gene therapy

Microarrays (gene chips) can examine gene expression in up to 50,000 different genes at once. It's mainly used for screening/gene discovery work. You screen 50,000 genes to discover an association and then you focus in on only a few hundred or so for more careful study by some other method. The "gold standard" for sensitivity and reproducibility is called real time polymerase chain reaction, or RT-PCR.

Genes make proteins, the molecules that comprise and maintain all the body's tissues. Genes produce their effect by sending molecules called messenger RNA to the protein-making machinery of a cell. They set the protein-making machinery in motion through a "gofer" messenger called RNA (or mRNA).

The technique called RNA interference (RNA-i) allows scientists to "silence" certain genes. In RNA interference, certain molecules trigger the destruction of RNA from a particular gene, so that no protein is produced. Thus, the gene is effectively silenced. RNA interference is already being widely used in basic science as a method to study the function of genes and it is being studied as a treatment for infections such as cancer.

RNA interference occurs naturally in plants, animals, and humans. RNA interference is important for regulating the activity of genes (a fundamental mechanism for controlling the flow of genetic information). RNA interference (RNAi) interferes with mRNA, a natural molecular switch, regulating gene expression in plants, animals and humans, by "silencing" over-active or malfunctioning genes.

The ability to transfect (introducing foreign DNA into a cell) cultured cells with DNA gene sequences has allowed us to assign functions to different genes and understand the mechanisms that activate or redress their function. It has made gene therapy and stem cell research possible.

Cell culture technology has revived many previously unattainable ambitions in medical science, including the Nobel prize winning discovery of RNA interference. Tissue culture methods have played a major part in the work of more than a third of the winners of the Nobel prize for medicine since 1953.

The key to understanding the genome is understanding how cells work. The ultimate driver is "functional" assay analysis (is the cell being killed regardless of the mechanism) as opposed to a "target" assay (does the cell express a particular target that the drug is supposed to be attacking). While a "target" assay tells you whether or not to give one drug, a "functional" assay can find other compounds and combinations and can recommend them from the one assay.

The core of the "functional" assay is the cell, composed of hundreds of complex molecules that regulate the pathways necessary for vital cellular functions. If a "targeted" drug could perturb any one of these pathways, it is important to examine the effects of the drug within the context of the cell. Both genomics and proteomics can identify potential new therapeutic "targets," but these "targets" require the determination of cellular endpoints.

Cell-based "functional" assays are being used for screening compounds for efficacy and biosafety. The ability to track the behavior of cancer cells permits data gathering on "functional" behavior not available in any other kind of assays.

Source: Cell Function Analysis