Purpose
We introduced a new concept of ex vivo gene expression analysis (Mitsuhashi, Clin Chem 53:148–149, 2007), where drug action was simulated under physiological conditions. This model system was applied to study
various fields of drug development.
Materials and Methods
Heparinized human whole blood was incubated with drugs for less than 4h. The changes of specific mRNA were then quantified
using the method we developed (Mitsuhashi, Tomozawa, Endo, and Shinagawa, Clin Chem 52:634–642, 2006).
Results
The mRNA quantitation method was used as a model system to study the following areas: (1) identification of respondents and
non-respondents, (2) ex vivo compound screening, (3) determination of individually optimized doses, (4) drug-to-drug comparison, (5) assessment of leukocyte
toxicity, (6) discovery of molecular targets, (7) assessment of the action of dietary supplements, and (8) characterization
of respondents and non-respondents for various dietary supplements.
Conclusion
Since ex vivo assays are safe, a large number of healthy donors and disease patients can be recruited to identify individual-to-individual
variations, which is not available from current preclinical study models. Although each system should be validated using a
large number of samples, the ex vivo analysis will be a new tool for the development of drugs and dietary supplements in future.
Key words blood - dietary supplement - drug development - gene expression - mRNA
Part of the study was presented at TriConference in 2007 in San Francisco.