Genetically Modified Models: Applications and limitations in drug discovery and development

The pharmaceutical industry is increasingly looking for new methods to increase the efficiency of R&D and improve the quality of the innovative new medicines produced. In recent years, modernization in the ability to produce genetically modified models have increase their use in drug discovery, both for the assessment of the function of genetic targets in vivo, and the predictive testing of the efficacy, pharmacokinetic and side effect profile of potential therapeutic agents. The study of gene-altered (knock-in/knock-out) and transgenic mice offers significant insights into the in vivo function and interaction of specific gene products. Within the pharmaceutical industry, genetically altered mice are used primarily in discovery research to illustrate the diverse functions of one or multiple gene products or to establish animal models of human disease for proof-of-concept studies. Transgenic and knockout mice also serves its purpose in drug development, because questions regarding risk assessment and carcinogenesis, xenobiotic metabolism, receptor- and ligand-mediated toxicity, and immunotoxicity can be assessed using these genetically altered model. The absolute inactivation of a gene may result in altered expression of related genes or physiologic compensation for the loss of the gene product. Consideration must also be given to the genetic environment of the mouse strain and the impact of strain variability on disease or toxicity models. Despite these likely constraints, genetically altered mice model provide a dominant tool for the advancement of drugs in the pharmaceutical industry.