Insulin genetic engineering

Tuch, B. E., Tabiin, M. T., Casamento, F. M., Simpson, A. M. and Marshall, G. M. (1998). Transplantation of genetically engineered insulin-producing hepatocytes into immunoincompetent mice. Transplant. Proc. 30, 473. 

Faster-Acting Insulin Genetic Engineering Solves a Qjiaternary Structure Problem... 

Insulin is one of the important pharmaceutical products produced commercially by genetically engineered bactera. Before this development, commercial insulin was isolated from animal pancreatic tissue. Microbial insulin has been available since 1982. The human insulin gene is introduced into a bacterium like E. coli. Two of the major advantages of insulin production by microorganisms are that the resultant insulin is chemically identical to human insulin, and it can be produced in unlimited quantities. 

The biopharmaceutical sector is largely based upon the application of techniques of molecular biology and genetic engineering for the manipulation and production of therapeutic macromolecules. The majority of approved biopharmaceuticals (described from Chapter 8 onwards) are proteins produced in engineered cell lines by recombinant means. Examples include the production of insulin in recombinant E. coli and recombinant S. cerevisiae, as well as the production of EPO in an engineered (Chinese hamster ovary) animal cell line. 

The expression of recombinant proteins in cells in which they do not naturally occur is termed heterologous protein production (Chapter 3). The first biopharmaceutical produced by genetic engineering to gain marketing approval (in 1982) was recombinant human insulin (tradename Humulin ), produced in E. coli. An example of a more recently approved biopharmaceutical that is produced in E. coli is that of Kepivance, a recombinant keratinocyte growth factor used to treat oral mucositis (Chapter 10). Many additional examples are provided in subsequent chapters. 

The toxicologist should be prepared to do nothing if the material is well-known, its properties are understood, and there is adequate characterization of the nature of the preparation supplied for example, human insulin or growth hormone produced by genetic engineering should not be submitted to prolonged safety tests in animals, provided that the molecular forms present are sufficiently well understood. 

Large quantities of pure insulin are required for the treatment of diabetes mellitus (see p. 160). The annual requirement for insulin is over 500 kg in a country the size of Germany. Formerly, the hormone had to be obtained from the pancreas of slaughtered animals in a complicated and expensive procedure. Human insulin, which is produced by overexpression in genetically engineered bacteria, is now mainly used (see p.262). 

Along with the production of insulin, many other medical uses have been achieved for recombinant DNA. This includes the production of erythropoetin, a hormone used to stimulate production of red blood cells in anemic people tissue plasminogen activator, an enzyme that dissolves blood clots in heart attack victims and antihemophilic human factor VIII, used to prevent and control bleeding for hemophiliacs. These three important genetically engineered proteins were all cloned in hamster cell cultures. 

The production of somatostatin, human insulin, a-interferon, the growth hormone, and erythropoietin are landmarks of the recent past of genetic engineering. 

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