Book contents
- Frontmatter
- Contents
- Preface
- Acknowledgements
- Read me first …
- Glossary
- Dedication
- Introduction: A disease for every gene?
- I From molecular biology to human genetics
- II From molecular genetics to human biochemistry
- III From molecular biochemistry to human cell biology
- IV From molecular cell biology to human physiology
- V From molecular physiology to human molecular biology
- 21 Genetic experimental systems
- 22 Gene and protein analysis
- 23 Genetic engineering, gene mapping, and gene testing
- 24 Gene knockouts, transgenics, and cloning
- 25 Gene therapy and recombinant DNA technology
- Index
25 - Gene therapy and recombinant DNA technology
Published online by Cambridge University Press: 01 June 2011
- Frontmatter
- Contents
- Preface
- Acknowledgements
- Read me first …
- Glossary
- Dedication
- Introduction: A disease for every gene?
- I From molecular biology to human genetics
- II From molecular genetics to human biochemistry
- III From molecular biochemistry to human cell biology
- IV From molecular cell biology to human physiology
- V From molecular physiology to human molecular biology
- 21 Genetic experimental systems
- 22 Gene and protein analysis
- 23 Genetic engineering, gene mapping, and gene testing
- 24 Gene knockouts, transgenics, and cloning
- 25 Gene therapy and recombinant DNA technology
- Index
Summary
Recombinant protein production
Synthetic human proteins are useful therapeutic agents
Which is easier to synthesize – a small steroid hormone like estrogen (molecular weight ∼300 daltons), or a multisubunit protein like plasminogen activator which, at 72 kDa, is more than 200 times larger?
Answer: the latter. Polypeptides are simple to make: a gene is transcribed, the message translated, and the resulting protein may not even require posttranslational modification. In other words, little intermediary metabolism is needed to produce most proteins; such products can be secreted directly into the milk of transgenic animals. Advantages of recombinant protein production over purification from source (e.g., from animals or human cadavers) include:
1. Greater consistency of product quality.
2. Higher efficiency of production.
3. Lower immunogenicity than animal proteins.
4. Reduced infectivity compared to tissue-derived products.
5. Genetic engineering of “super proteins” with high activity.
A singular disadvantage of recombinant technology is that such proteins are difficult to detect when used for illicit purposes – the abuse of erythropoietin and growth hormone by athletes is a case in point.
In the transplant setting, animal tissues may be rejected because of species-specific differences in post-translational protein modification, particularly glycosylation. Attempts to improve the take of porcine grafts, for example, have centered on knocking out a pig-specific galactosyltransferase. Recombinant monoclonal antibodies derived from mice are re-engineered for human therapeutic use by humanizing those parts of the Fab domains between the complementarity-determining regions (Figure 25.2), thereby reducing the immunogenicity of transfused antibodies.
- Type
- Chapter
- Information
- Human Molecular BiologyAn Introduction to the Molecular Basis of Health and Disease, pp. 587 - 602Publisher: Cambridge University PressPrint publication year: 2002