The R&D productivity gap, or the increasing amount of pharmaceutical R&D spending relative to the number of new drug candidates introduced per year, has been widely discussed in the industry and media. Many companies are responding by reexamining the tools, techniques, and practices used in drug discovery and development. This introspection has highlighted the need for more physiologically relevant technologies, particularly in discovery.
Today, much of the discovery process revolves around high-throughput screening (HTS) techniques, and a multibillion-dollar industry has appeared to supply researchers with a broad range of solutions. HTS has matured to the point where approximately half of all assays performed are cell-based and the remainder biochemical.
Despite the large number of available tools, important limitations persist for both assay classes. For example, biochemical assays frequently rely on fluorescent or radioactive labeling techniques that present a number of possible pitfalls.
In particular, labels can interfere with the interaction between analyte and target, producing misleading results. Labels are often difficult or tedious to properly affix and, in still other cases, the natural ligand for a given target may not be known.
Solutions providers have developed a range of label-free technologies to address the limitations associated with labels, but thus far these solutions have been unable to achieve the throughput needs of modern discovery programs.
Similarly, many cell-based assays require development (or licensing) of engineered cell lines that over express a target of interest to provide a sufficiently large signal response for detection with the available technologies. While use of these highly engineered cell lines enables the detection of a response, it comes at the expense of making the resulting assay less physiologically relevant to the disease being investigated.