Target Identification & Validation

Thanks in large part to the Human Genome Project and the dramatic drop in the cost of DNA sequencing, scientists can sort through the roughly 35,000 genes in the human genome to identify sites linked to disease. Discoveries of the molecular basis of diseases point to exciting potential pathways for developing new and better treatments.

Most drugs block the action of a particular target protein or cell structure. The only way to be completely certain that a protein is instrumental in a given disease is to test that idea in humans. Obviously, scientists cannot use human clinical trials in the early phases of drug development; therefore, a potential target protein must undergo a validation process. That is, researchers must clearly define the protein’s role in a disease before looking for drugs that act against it or before using it to screen large numbers of compounds for drug activity.

Not so long ago, potential drug targets were hard to come by; now the pharmaceutical industry has too many to count. Researchers must sift through vast amounts of data in search of proteins that could be instrumental in human disease — too many potential leads to evaluate one at a time. At NCATS, the goal is to prioritize targets based on how likely they are to lead to a promising therapeutic.

The NCATS Approach

NCATS supports efforts to develop new methods, approaches, tools and technologies to validate targets in a more efficient and predictable fashion, positioning promising leads at the start of a drug development path that produces safe and effective products.

The Center hosts state-of-the-art RNA interference (RNAi) screening capabilities to support target identification and validation. NCATS’ RNAi experts assist investigators from other NIH Institutes and Centers with all stages of project planning and execution, from assay development and genome-wide siRNA screens to informatics, pathway analysis and rigorous follow-up. The facility can produce genome-wide siRNA screens for humans and mice, and microRNA mimic and inhibitor libraries are routinely included.

NCATS scientists have in-depth expertise with RNA editing technologies and cell line engineering, and they also perform research to advance the science of RNAi screening technologies. The Center’s assay development capabilities in service of target identification and validation include assay design, optimization, validation and miniaturization.