Development: In Vivo Pharmacology—Systems Biology in Health and Disease II

  • Aleš Prokop
  • Seth Michelson
Part of the SpringerBriefs in Pharmaceutical Science & Drug Development book series (BRIEFSPSDD, volume 2)


This chapter covers qualitative in vivo approaches in animals and man, which will help to develop in silico pharmacology and PK positions. Additionally, we cover RNA interference in this chapter even though it is largely an in vitro method for characterizing the dynamics of cell physiology. And though in silico pharmacology is only in a rudimentary state, it is vitally important for clinical model based drug design (MBDD) development (see Chap. 10).


Humanize Mouse Animal Disease Model Xenobiotic Receptor Virtual Ligand Screening Adaptive Trial Design 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Brown SD, Hancock JM (2006) The mouse genome. Genome Dyn 2:33–45PubMedCrossRefGoogle Scholar
  2. 2.
    Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7(2):118–130PubMedCrossRefGoogle Scholar
  3. 3.
    Gondo Y (2008) Trends in large-scale mouse mutagenesis: from genetics to functional genomics. Nat Rev Genet 9(10):803–810PubMedCrossRefGoogle Scholar
  4. 4.
    Kissler S, Van Parijs L (2004) Exploring the genetic basis of disease using RNA interference. Expert Rev Mol Diagn 4(5):645–651PubMedCrossRefGoogle Scholar
  5. 5.
    Lewandoski M (2001) Conditional control of gene expression in the mouse. Nat Rev Genet 2(10):743–755PubMedCrossRefGoogle Scholar
  6. 6.
    Nebert DW, Jorge-Nebert L, Vesell ES (2003) Pharmacogenomics and “individualized drug therapy”: high expectations and disappointing achievements. Am J Pharmacogenomics 3(6):361–370PubMedCrossRefGoogle Scholar
  7. 7.
    Tomalik-Scharte D, Lazar A, Fuhr U, Kirchheiner J (2008) The clinical role of genetic polymorphisms in drug-metabolizing enzymes. Pharmacogenomics J 8(1):4–15PubMedCrossRefGoogle Scholar
  8. 8.
    Zhou J, Rossi JJ (2011) Aptamer-targeted RNAi for HIV-1 therapy. Methods Mol Biol 721:355–371PubMedCrossRefGoogle Scholar
  9. 9.
    Thiel KW, Giangrande PH (2010) Intracellular delivery of RNA-based therapeutics using aptamers. Ther Deliv 1(6):849–861PubMedCrossRefGoogle Scholar
  10. 10.
    Blagbrough IS, Zara C (2009) Animal models for target diseases in gene therapy—using DNA and siRNA delivery strategies. Pharm Res 26(1):1–18PubMedCrossRefGoogle Scholar
  11. 11.
    Colombo R, Moll J (2008) Target validation to biomarker development: focus on RNA interference. Mol Diagn Ther 12(2):63–70PubMedGoogle Scholar
  12. 12.
    Reynolds A, Leake D, Boese Q, Scaringe S, Marshall WS (2004) Rational siRNA design for interference. Nat Biotechnol 22(3):326–330PubMedCrossRefGoogle Scholar
  13. 13.
    Patzel V (2007) In silico selection of active siRNA. Drug Discov Today 12(3–4):139–148PubMedCrossRefGoogle Scholar
  14. 14.
    Liao G, Zhang X, Clark DJ, Peltz G (2008) A genomic “roadmap” to “better” drugs. Drug Metab Rev 40(2):225–239PubMedCrossRefGoogle Scholar
  15. 15.
    Yan Q (2008) The integration of personalized and systems medicine: bioinformatics support for pharmacogenomics and drug discovery. Methods Mol Biol 448:1–19PubMedCrossRefGoogle Scholar
  16. 16.
    Sheiner LB (1997) Learning versus confirming in clinical drug development. Clin Pharmacol Ther 61:275–291PubMedCrossRefGoogle Scholar
  17. 17.
    Simon R (2008) The use of genomics in clinical trial design. Clin Cancer Res 14(19):5984–5993PubMedCrossRefGoogle Scholar
  18. 18.
    Ekins S, Mestres J, Testa B (2007) In silico pharmacology for drug discovery: applications to targets and beyond. Br J Pharmacol 152(1):21–37PubMedCrossRefGoogle Scholar
  19. 19.
    Ekins S, Mestres J, Testa B (2007) In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. Br J Pharmacol 152(1):9–20PubMedCrossRefGoogle Scholar
  20. 20.
    Johnson AD, Wang D, Sadee W (2005) Polymorphisms affecting gene regulation and mRNA processing: broad implications for pharmacogenetics. Pharmacol Ther 106(1):19–38PubMedCrossRefGoogle Scholar
  21. 21.
    Fielden MR, Matthews JB, Fertuck KC, Halgren RG, Zacharewski TR (2002) In silico approaches to mechanistic and predictive toxicology: an introduction to bioinformatics for toxicologists. Crit Rev Toxicol 32(2):67–112PubMedCrossRefGoogle Scholar
  22. 22.
    Noble D (2003) The future: putting Humpty-Dumpty together again. Biochem Soc Trans 31(Pt1):156–158PubMedGoogle Scholar
  23. 23.
    Michelson S (2006) The impact of systems biology and biosimulation on drug discovery and development. Mol Biosyst 2(6–7):288–291PubMedCrossRefGoogle Scholar
  24. 24.
    Guo Y, Shafer S, Weller P, Usuka J, Peltz G (2005) Pharmacogenomics and drug development. Pharmacogenomics 6(8):857–864PubMedCrossRefGoogle Scholar

Copyright information

© The Author(s) 2012

Authors and Affiliations

  1. 1.Chemical and Biomolecular EngineeringVanderbilt UniversityNashvilleUSA
  2. 2.NanoDelivery International, s.r.o.Břeclav-PoštornáCzech Republic
  3. 3.Genomic Health IncRedwood CityUSA

Personalised recommendations