Gene manipulation and recombinant DNA technology - Pharmaceutical Biotechnology: Concepts and Aapplications - page 56

Table 3.3 Some approved biopharmaceuticals that have been altered by post-translational engineering

Engineered product Effect of engineering

Insulin 'Detemir' (insulin with a fatty acid molecule
attached; Chapter 11)

The insulin has a prolonged duration of action

PEGylated interferons (interferons to which
polyethylene glycol molecules have been covalently
attached; Chapter 8)

Increases product serum half-life, thereby reducing
the frequency of dosage

Carbohydrate remodelled glucocerebrosidase
(Cerezyme; Chapter 12)

Generation of product that is specifi cally targeted for
uptake by macrophages

used to tailor structural or functional attributes of therapeutic and other commercially important
proteins.
An increasing proportion of therapeutic proteins gaining approval for general medical use
display an engineered amino acid sequence, altered in order to fulfi l a predefi ned therapeutic
goal better. Selected examples of biopharmaceuticals engineered in this way are presented in
Table 1.3, and these, along with additional examples, will be discussed in various subsequent
chapters. An alternative approach to protein engineering entails the covalent attachment or the
alteration of specifi c molecules/groups to or on the polypeptide's backbone (Table 3.3). Specifi c
examples of such post-translational engineering will again be provided in subsequent chapters.

Further reading

Books

Brown, T. 2006. Gene Cloning and DNA Analysis, an Introduction . Blackwell Science, UK.
Gellissen, G (ed.). 2005. Production of Recombinant Proteins . Wiley-VCH, Germany.
Primrose, S.B., Twyman, R.M., and Old, R.W. 2001. Principles of Gene Manipulation , 6th edn. Blackwell Science,
UK.
Sambrook, J. and Russell, D. 2006. Condensed Protocols from Molecular Cloning: A Laboratory Manual . Cold
Spring Harbor Laboratory Press, USA.

Articles

Abramowicz, M. 2003. The human genome project in retrospect. Perspectives on Properties of the Human Ge-
nome Project 50 , 231-261.
Arya, M., Shergill, I.S., Williamson, M., Gommersall, L., Arya, N., and Patel, H.R. 2005. Basic principles of real
time quantitative PCR. Expert Review of Molecular Diagnostics 5 , 209-219.
Brannigan, J. and Wilkinson, A. 2002. Protein engineering 20 years on. Nature Reviews Molecular Cell Biology
3 , 964-970.
Christensen, A. 2001. Bacteriophage lambda-based expression vectors. Molecular Biotechnology 17 , 219-224.
Feuk, L., Carson, A.R., and Scherer, S.W. 2006. Structural variation in the human genome. Nature Reviews
Genetics 7 , 85-97.