The application of RAGE and GECKO in cell-based target discovery screens.
While significant advancements have been made in identifying the genes that comprise the human genome, considerable work remains in gaining an understanding of the functions of these gene products. Improved knowledge of protein function is of particular relevance to the drug discovery process, as the elucidation of new targets that are involved in disease processes will most probably lead to improvements in health care. Reverse genetic approaches that attempt to assign protein function on a gene-by-gene basis are labor intensive and have low throughput. Although forward genetic (function-to-gene) approaches often allow for the more efficient identification of disease-relevant drug targets, most existing methodologies are not capable of sampling the entire genome. Here we review current target discovery strategies and discuss two relatively new technologies, RAGE (random activation of gene expression) and GECKO (genome-wide cellular knockout). These tools provide cellular libraries that can be utilized in genome-wide target discovery screens. Examples are given of how these methodologies may facilitate the identification of new drug targets that are involved in human disease and pathology.
Brunden
Kr
K
Athersys, Inc., 3201 Carnegie Avenue, Cleveland, OH 44115, USA. kbrunden@athersys.com
Sherf
Ba
B
Harrington
Jj
J
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D016678:Genome; D006801:Humans; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D030781:Organisms, Genetically Modified / Q000235:genetics*; D010597:Pharmacogenetics / Q000379:methods*